Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series

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Abstract

Background: Tuberculosis remains a significant public health issue in Tunisia. This study aimed to describe the epidemiological, clinical, and therapeutic characteristics of cervical lymph node tuberculosis and identify factors influencing outcomes. Methods A retrospective study was conducted over a 3-year period in the ENT department at La Rabta Hospital, Tunis. Diagnosis was based on histopathological evidence, and disease progression was categorized as favorable (treatment 9 months and/or supplementary surgery). The study population was divided into two groups based on the outcome nature, and analytical analysis was performed to assess factors influencing outcomes Results The study included 102 patients (32 men and 70 women), with a median age of 34.5 years (range: 8-83 years). Most patients (78.4%) had no significant medical history or known HIV infection. Thirty-nine patients (38.2%) had a history of consuming raw milk. In 65 cases (63.7%), lymph node size exceeded 3 cm. Hypoechogenicity (53.9%) and necrosis (40.1%) were the most common findings on ultrasound and CT scan, respectively. The initial diagnostic approach included adenectomy (56.8%), lymph node dissection (8.9%), and drainage of cold abscesses (34.3%). All patients received an initial four-drug antituberculosis regimen. Ethambutol treatment was extended beyond 2 months in 65 cases (63.7%). Fifty-six patients (54.9%) had a favorable outcome. Factors associated with a favorable outcome included intact skin, complete initial lymph node dissection, favorable progress at 2 months, and prolonged ethambutol therapy. Conclusions The management of lymph node tuberculosis remains challenging, especially with insufficient bacteriological confirmation. Regional epidemiological factors should be considered. The role of surgery is crucial; however, further standardization is needed to optimize patient outcomes.
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This study aimed to describe the epidemiological, clinical, and therapeutic characteristics of cervical lymph node tuberculosis and identify factors influencing outcomes. Methods A retrospective study was conducted over a 3-year period in the ENT department at La Rabta Hospital, Tunis. Diagnosis was based on histopathological evidence, and disease progression was categorized as favorable (treatment 9 months and/or supplementary surgery). The study population was divided into two groups based on the outcome nature, and analytical analysis was performed to assess factors influencing outcomes Results The study included 102 patients (32 men and 70 women), with a median age of 34.5 years (range: 8-83 years). Most patients (78.4%) had no significant medical history or known HIV infection. Thirty-nine patients (38.2%) had a history of consuming raw milk. In 65 cases (63.7%), lymph node size exceeded 3 cm. Hypoechogenicity (53.9%) and necrosis (40.1%) were the most common findings on ultrasound and CT scan, respectively. The initial diagnostic approach included adenectomy (56.8%), lymph node dissection (8.9%), and drainage of cold abscesses (34.3%). All patients received an initial four-drug antituberculosis regimen. Ethambutol treatment was extended beyond 2 months in 65 cases (63.7%). Fifty-six patients (54.9%) had a favorable outcome. Factors associated with a favorable outcome included intact skin, complete initial lymph node dissection, favorable progress at 2 months, and prolonged ethambutol therapy. Conclusions The management of lymph node tuberculosis remains challenging, especially with insufficient bacteriological confirmation. Regional epidemiological factors should be considered. The role of surgery is crucial; however, further standardization is needed to optimize patient outcomes. 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F1000Research 2025, 14 :511 ( https://doi.org/10.12688/f1000research.164097.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] Maissa Lajhouri https://orcid.org/0009-0000-5656-0208 1 , Selima Jouini 1 , Yosra Ammar Mnejja https://orcid.org/0009-0008-7563-2164 1 , Azza Mediouni 1 , Rihab Lahmar 1 , Houda Chahed 1 Maissa Lajhouri https://orcid.org/0009-0000-5656-0208 1 , Selima Jouini 1 , [...] Yosra Ammar Mnejja https://orcid.org/0009-0008-7563-2164 1 , Azza Mediouni 1 , Rihab Lahmar 1 , Houda Chahed 1 PUBLISHED 30 Sep 2025 Author details Author details 1 Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia Maissa Lajhouri Roles: Conceptualization, Methodology, Writing – Review & Editing Selima Jouini Roles: Writing – Original Draft Preparation Yosra Ammar Mnejja Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation Azza Mediouni Roles: Validation Rihab Lahmar Roles: Validation Houda Chahed Roles: Validation OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Pathogens gateway. Abstract Background Tuberculosis remains a significant public health issue in Tunisia. This study aimed to describe the epidemiological, clinical, and therapeutic characteristics of cervical lymph node tuberculosis and identify factors influencing outcomes. Methods A retrospective study was conducted over a 3-year period in the ENT department at La Rabta Hospital, Tunis. Diagnosis was based on histopathological evidence, and disease progression was categorized as favorable (treatment 9 months and/or supplementary surgery). The study population was divided into two groups based on the outcome nature, and analytical analysis was performed to assess factors influencing outcomes Results The study included 102 patients (32 men and 70 women), with a median age of 34.5 years (range: 8-83 years). Most patients (78.4%) had no significant medical history or known HIV infection. Thirty-nine patients (38.2%) had a history of consuming raw milk. In 65 cases (63.7%), lymph node size exceeded 3 cm. Hypoechogenicity (53.9%) and necrosis (40.1%) were the most common findings on ultrasound and CT scan, respectively. The initial diagnostic approach included adenectomy (56.8%), lymph node dissection (8.9%), and drainage of cold abscesses (34.3%). All patients received an initial four-drug antituberculosis regimen. Ethambutol treatment was extended beyond 2 months in 65 cases (63.7%). Fifty-six patients (54.9%) had a favorable outcome. Factors associated with a favorable outcome included intact skin, complete initial lymph node dissection, favorable progress at 2 months, and prolonged ethambutol therapy. Conclusions The management of lymph node tuberculosis remains challenging, especially with insufficient bacteriological confirmation. Regional epidemiological factors should be considered. The role of surgery is crucial; however, further standardization is needed to optimize patient outcomes. READ ALL READ LESS Keywords tuberculosis, lymphadenopathy, tuberculous lymphadenitis, Mycobacterium Bovis, outcome. Corresponding Author(s) Maissa Lajhouri ( [email protected] ) Close Corresponding author: Maissa Lajhouri Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Lajhouri M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Lajhouri M, Jouini S, Ammar Mnejja Y et al. Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.12688/f1000research.164097.2 ) First published: 21 May 2025, 14 :511 ( https://doi.org/10.12688/f1000research.164097.1 ) Latest published: 30 Sep 2025, 14 :511 ( https://doi.org/10.12688/f1000research.164097.2 ) Revised Amendments from Version 1 This new version of the article includes important revisions compared to the previously published version. The Introduction has been expanded to incorporate additional local data on lymph node tuberculosis in Tunisia, providing a clearer epidemiological context. In the Results section, cytopathological findings have been elaborated and presented in a detailed table, illustrating the different patterns observed and their diagnostic relevance. The Discussion has been refined to integrate these findings with recent literature, and references regarding cytopathology have been added. Furthermore, reviewer comments have been addressed, including clarifications regarding HIV testing. Limitations such as small sample size and low bacteriological confirmation are now explicitly acknowledged in the Conclusion. These revisions improve the clarity, scientific rigor, and clinical relevance of the article, offering a more comprehensive understanding of lymph node tuberculosis and its management. This new version of the article includes important revisions compared to the previously published version. The Introduction has been expanded to incorporate additional local data on lymph node tuberculosis in Tunisia, providing a clearer epidemiological context. In the Results section, cytopathological findings have been elaborated and presented in a detailed table, illustrating the different patterns observed and their diagnostic relevance. The Discussion has been refined to integrate these findings with recent literature, and references regarding cytopathology have been added. Furthermore, reviewer comments have been addressed, including clarifications regarding HIV testing. Limitations such as small sample size and low bacteriological confirmation are now explicitly acknowledged in the Conclusion. These revisions improve the clarity, scientific rigor, and clinical relevance of the article, offering a more comprehensive understanding of lymph node tuberculosis and its management. See the authors' detailed response to the review by Sufian Zaheer See the authors' detailed response to the review by Vatsal Bhushan Gupta See the authors' detailed response to the review by Ma Jalil Chowdhury and M Mainul Hasan Chowdhury Lt. Col. Chowdhury Lt. Col. READ REVIEWER RESPONSES Introduction Tuberculosis continues to be a major health problem, with an incidence rate of over 10 million cases per year worldwide. 1 This disease causes significant morbidity and has a considerable mortality rate, estimated at around 1.3 million deaths, making tuberculosis the second most lethal infectious disease after COVID-19 in 2022. 1 Lymph node tuberculosis is the most common manifestation of extrapulmonary tuberculosis, with the cervical area being the most frequently involved. 2 Cervical lymph node tuberculosis can present real diagnostic and therapeutic challenges due to its paucibacillary nature and the increasing rate of resistance to antituberculosis drugs. In Tunisia, tuberculosis remains endemic despite the National Tuberculosis Control Program implemented since 1959, with an annual incidence estimated at 38 per 100,000 in 2023 (WHO). 3 Unlike pulmonary tuberculosis, whose incidence has remained relatively stable over the years, lymph node tuberculosis has experienced an increasing incidence, rising from 2.3 per 100,000 in 1993 to 18 per 100,000 in 2017, with substantial regional disparities. 4 – 6 The aim of this study was to describe the epidemiological, clinical, and therapeutic features of cervical tuberculous lymphadenitis and to evaluate the potential factors influencing the course of the disease. Methods Study design and participants This is a retrospective study conducted over a 3-year period, from 2019 to 2021. We reviewed clinical data from patients with cervical tuberculous lymphadenitis treated in the Head and Neck Surgery Department at La Rabta Hospital in Tunis. The diagnosis of tuberculous lymphadenitis was based on histopathological findings in all patients. Initially, all patient records diagnosed with cervical tuberculous lymphadenitis were extracted. Patients who met the exclusion criteria were subsequently removed from the study. The exclusion criteria were as follows: • Patients with poor adherence to treatment • Patients who were not fully followed up in our department The minimum follow-up period was 12 months after the completion of treatment. Evolution assessment The progression was assessed based on two criteria: the duration of treatment and the need for a second surgical procedure to complete the treatment. These two criteria were used to divide the population into two groups: those with a favorable outcome (G1), defined as a treatment duration of less than 9 months without the need for surgical treatment and a lymph node size of less than 1 cm at the end of treatment, and those with an unfavorable outcome (G2), if the treatment lasted more than 9 months and/or if a second surgery was required. The limit of 9 months was chosen to assess prognosis because, in some cases, the treatment was maintained for more than 6 months as imaging was not immediately available to control the lymph node size, or in the presence of residual adenopathy. Recurrence was defined as the reappearance of tuberculous lymphadenitis or an increase in the size of lymphadenopathy after the completion of treatment, confirmed by bacteriological, molecular, cytological, or histopathological evidence. The minimum period after treatment completion required to define recurrence was 6 months of remission. Statistical methods Data analysis The clinical profiles of the enrolled patients were described using descriptive statistics, including mean values, standard deviations, medians, and interquartile ranges for continuous variables, and proportions for categorical variables. An analytical study was conducted to compare two groups of patients to identify factors potentially associated with favorable or unfavorable disease progression. Epidemiological, clinical, biological, radiological, and therapeutic factors were evaluated. Univariate analysis - Comparisons between two qualitative variables were performed using Pearson’s chi-squared test, or Fisher’s exact test when assumptions for the chi-squared test were not met. - Comparisons between one qualitative variable and one quantitative variable were conducted using: ○ Student’s t-test for variables following a Gaussian distribution (normality tested using the Shapiro-Wilk test). ○ Non-parametric tests (e.g., Mann-Whitney U test) for variables not following a Gaussian distribution. - Odds Ratios (OR) were calculated for qualitative variables to estimate risk factors. Multivariate analysis A multivariate analysis was conducted using a logistic regression model (or Cox regression for survival data). Variables with p < 0.2 in univariate analysis were included. The results were expressed as Odds Ratios (OR) with 95% Confidence Intervals (CI). Statistical analysis was performed using SPSS version 22. A p-value < 0.05 was considered statistically significant. Results Descriptive analysis A total of 161 cases of cervical lymph node tuberculosis were initially diagnosed, but only 102 patients were ultimately included. The group included 32 men and 70 women, with a sex ratio of 0.46. The median age was 34.5 years (range: 8-83). Sixty-one patients (60%) were under the age of forty. Only 22 patients (21.5%) had a special medical history (hypertension, diabetes, pulmonary tuberculosis, autoimmune diseases: Systemic lupus erythematosus, Behçet’s disease, Crohn’s disease, thyroiditis). No cases of known human immunodeficiency virus (HIV) infection were reported. Thirty-nine patients (38.2%) had a history of consuming raw milk. Tuberculosis was discovered during the exploration of systemic symptoms in 59 patients (57.8%), while 40 patients (39.2%) presented with neck swelling as the first complaint. Two patients were already under treatment for pulmonary and one patient for osteoarticular tuberculosis, and cervical lymphadenitis was detected on radiological examination. On physical examination, 86 patients (84.3%) had multiple palpable nodes, mostly unilateral (76 patients: 74.5%). The most affected lymph node levels were II and III (94 patients: 92.1%). The median size of the lymph nodes was 3 cm (range: 1.5 cm to 7.5 cm). In 65 cases (63,7%), lymph node size exceeded 3 cm. The skin was inflammatory in 28 cases (27.4%) and a cutaneous sinus tract was present in 9 cases (8.8%) ( Figure 1 ). Figure 1. Clinical Features of Tuberculous Lymphadenopathy. (a) Lymph node in level IIa (arrow), firm, mobile, painless, covered by healthy skin. (b) Multiple jugulo-carotid and spinal lymph nodes: level Vb node fistulized to the skin. (c) Right parotid region lymph node, soft, covered by healthy skin. (d) Multiple lymph nodes in levels II and III, soft, covered by healthy skin. (e) Multiple lymph nodes in levels II and III, soft, tender, covered by inflamed skin. (f) Lower spinal lymph node, soft and tender, covered by inflamed skin with an adjacent fistula. Biological tests revealed anemia in 25 patients (24.5%) and lymphopenia in 22 patients (21.5%). HIV testing was performed in only three patients, and all tests were negative. The tuberculin skin test was performed in 88 patients (86.2%). An induration or erythema diameter greater than 10 mm was observed in 75 patients. All patients had cervical ultrasound (US) and/or computed tomography (CT) of the neck and thorax. The most prevalent radiological features were hypo echogenicity on US (53.9%) and necrosis on CT (40.1%) ( Figure 2 ). Figure 2. Multiple Necrotic Cervical Lymphadenopathies on CT Scan. Imaging revealed the involvement of extra cervical lymph nodes in 22 patients (21.5%), particularly in the mediastinum (15 patients), and associated pulmonary tuberculosis in three patients. Fine needle aspiration (FNA) was performed in 85 patients (83.3%). Epithelioid granulomas with necrosis were observed in 33 patients ( Table 1 bis ). Table 1 bis. Cytomorphological patterns. Cytopathological patterns Number of cases Epithelioid granuloma with necrosis 33 Necrosis only 25 Epithelioid granuloma without necrosis 8 Inconclusive 19 Microbiological testing was performed in 21 patients (20.6%). It revealed the presence of Acid-fast Bacilli on direct microscopic examination in 6 patients, but mycobacterium tuberculosis cultures were negative in all cases. Molecular tests using the Xpert/MT PCR technique were carried out in 21 patients (20.6%) and were positive for Mycobacterium tuberculosis in 16 patients. Intermediate resistance to rifampicin was found in 7 patients. Surgery associated with histopathological study was performed in all patients. The surgical procedures consisted of lymphadenectomy in 58 patients (56.8%), lymph node dissection in 9 patients (8.9%), and drainage of abscess with curettage/or fistula excision in 35 patients (34.3%) ( Figure 3 ). Figure 3. Surgical Procedures. • 3A: Lymph Node Dissection. • 3B: Lymphadenectomy. A four-drug regimen (isoniazid, rifampicin, pyrazinamide, ethambutol) was systematically administered for two months. The following two-drug regimen (mainly Isoniazid + Rifampicin) was prescribed. Ethambutol was maintained for more than two months, with an average duration of 4 months (range: 2–12 months) in 65 patients (63.7%). Eleven patients received second-line antituberculosis drugs, consisting of fluoroquinolones. By the second month of treatment, compared to the initial size of the lymphadenopathy, clinical improvement was observed in 51 patients (50%), stable lymph node size in 32 patients (31.3%), and a paradoxical reaction in 15 patients (14.7%). The outcome was considered favorable in 56 patients (G1) and unfavorable in 46 patients (G2). In G2, two patients required surgery with a total treatment duration of less than 9 months, 22 patients received anti-tuberculous treatment for more than 9 months, and the remaining 22 patients underwent surgery along with prolonged treatment. Tuberculosis recurrence was observed in 12 patients (11.7%), with a median delay of 12 months (range: 7–63 months). These patients were predominantly G2 (11 patients: 91.6%). Statistical analysis Univariate analysis (Table 1 Underlying data 7 ) revealed that the epidemiological characteristics and medical history were not significantly associated with any specific disease progression. Analysis of physical examination data showed that pathological skin conditions (inflammatory skin/fistula) were significantly associated with unfavorable disease progression. No biological criteria were found to influence the outcome. Regarding imaging data, significant association was found between lymph node necrosis on CT and unfavorable disease progression. When the initial procedure involved abscess drainage, patients were more likely to experience an unfavorable outcome. However, if the initial procedure was lymph node dissection, patients were twice as likely to have a favorable outcome. The presence of intermediate resistance to rifampicin did not influence disease progression. Prolonged ethambutol prescription beyond the first two months of treatment was significantly associated with a favorable disease outcome. Patients showing improvement by the second month were more likely to achieve a favorable outcome. Multivariate analysis ( Tables 2 and 3 ) revealed that pathological skin conditions, necrosis on CT, abscess drainage, occurrence of a paradoxical reaction, and lack of improvement by the end of the second month of treatment were independently associated with an unfavorable outcome. On the other hand, healthy skin adjacent to the lymph nodes, initial lymph node dissection, favorable evolution at the end of the second month of treatment, and prolonged ethambutol prescription beyond two months were factors independently associated with a favorable disease outcome. Table 2. Multivariate Analysis of Factors Associated with Unfavorable Outcomes. Factors associated with unfavorable evolution P Odds Ratio 95% Confidence Interval Lower Higher Pathological adjacent skin 0.024 3.496 1.177 10.380 Necrosis on cervical CT scan 0.044 2.406 1.024 5.651 Drainage of a cold abscess 0.029 3.306 1.132 9.653 Paradoxical reaction (end of the second month) 0.002 9.633 2.285 40.613 Stagnation (end of the second month) 0.000 11.776 3.591 38.617 Table 3. Multivariate Analysis of Factors Associated with Favorable Outcomes. Factors associated with favorable evolution P Odds Ratio 95% Confidence Interval Lower Higher Healthy adjacent skin 0.006 3.637 1.452 9.113 Lymph node dissection 0.030 4.069 1.146 14.442 Improvement (end of the second month) 0.003 19.482 2.735 85.434 Prolonged ethambutol treatment 0.002 4.339 1.697 11.093 All data supporting these findings are publicly available through Zenodo (DOI: 10.5281/zenodo.15351592 ) 7 Discussion Tunisia is classified as a country with intermediate tuberculosis endemicity, with an estimated annual incidence between 50 and 99 cases per 100,000 inhabitants. 1 This relatively high incidence, coupled with increasing challenges in disease management, particularly in cases of cervical lymph node tuberculosis, highlights the importance of addressing this pathology. Descriptive analysis Among the 102 study participants, most of the patients (61, or 60%) were under the age of 40 years. This finding is consistent with several published reports. 2 , 8 , 9 Furthermore, like other studies, a female predominance was observed, in contrast to the clear male predominance in pulmonary tuberculosis. 2 , 8 The reasons for this female prevalence remain unexplained. Some patients had autoimmune diseases, including Crohn’s disease. Certain treatments, such as tumor necrosis factor (TNF) antagonists, are now known to affect the antituberculosis immune response. 10 , 11 The HIV-positive population was not represented in our study, as individuals with known HIV infection and tuberculous lymphadenitis are followed up in the infectious disease department at our institution. Moreover, only a few patients were tested for HIV. No conclusions can be drawn regarding HIV infection from our series, although many studies have reported a low HIV positivity rate in patients with tuberculous lymphadenopathy. 2 , 9 , 12 – 14 However, although Tunisia has a low incidence of HIV—albeit recently increasing 15 —and a low HIV positivity rate among patients with tuberculous lymphadenopathy in published series, we recommend HIV testing in cases of tuberculous lymph node involvement, particularly in the presence of an unfavorable outcome. In our study, a significant percentage of participants (38.2%) reported raw milk consumption, similar to other studies, suggesting that Mycobacterium Bovis strains may contribute to tuberculous lymphadenitis in certain regions. 8 , 16 , 17 Most patients had unilateral and multiple lymph node involvement. In their studies, Mathiasen et al. and Qian et al. reported unilateral involvement in most cases. 14 , 18 However, cervical tuberculous lymphadenitis can be unilateral or bilateral, and all lymphatic levels of the neck can be affected. Tuberculosis can present with various cytopathological patterns on fine-needle aspiration (FNA): granulomas with necrosis, granulomas without necrosis, and necrosis alone, with the first pattern being the most common and most highly suggestive of tuberculosis. 19 In our series, 32.3% of cases showed epithelioid granulomas with necrosis on FNA; however, all patients were ultimately treated based on histopathological findings indicative of tuberculosis. This approach could be explained by the low positivity rate of bacteriological tests, the concern of misdiagnosing a malignancy, and, in some cases, the need for surgery in patients with abscesses or sinus tract formation. Despite their high sensitivity, cytology and histopathology lack specificity for extrapulmonary tuberculosis, as granulomas can also be present in other diseases, such as nontuberculous mycobacterial infections. 20 FNA is considered the first-line of investigation for tuberculous lymphadenitis because it is cost-effective, safe and rapid, particularly in endemic countries with limited resources. 19 – 22 However, diagnosing tuberculosis solely on cytological or histopathological criteria should be approached with caution, and careful correlation with clinical and radiological data is essential to establish an accurate diagnosis. 23 The isolation of Mycobacterium tuberculosis remains the gold standard for a confirmatory diagnosis of tuberculous lymphadenitis, either through culture or by PCR testing of a sample from an affected lymph node. 24 The culture positivity rate was low in our study. In fact, the rate of culture positivity in lymph node tuberculosis ranges from 18% to 62%. 24 The Xpert® MTB/RIF assay was the only molecular test performed, conducted in 20.6% of cases, likely due to availability issues. This targeted PCR technique, by detecting the Mycobacterium tuberculosis complex, provides a rapid diagnosis with greater sensitivity than culture and high specificity. It also detects the rifampicin resistance gene, which was found in 7 of our patients (6.8%). Other multiplex PCRs, detecting more resistance mutations on target genes, exist but are unavailable in hospital laboratories in Tunisia. Next-generation sequencing, which enables the simultaneous sequencing of multiple genes, is becoming increasingly available in many countries. The widespread adoption of these techniques in resource-constrained countries could be crucial for implementing more effective anti-tuberculosis therapy. 20 , 25 Treatment of active tuberculosis involves a well-established two-phase approach: an initial two-month, four-drug regimen (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) followed by a maintenance phase with a two-drug regimen (Isoniazid, Rifampicin). The World Health Organization (WHO) recommends a treatment duration of six months for lymph node tuberculosis caused by sensitive strains. However, the treatment duration may extend beyond this period, with many studies reporting durations exceeding six months. 24 , 26 , 27 There remains controversy regarding the treatment duration for tuberculous lymphadenitis, as the course of the disease is unpredictable and there are no clear criteria for assessing cure. 27 In Tunisia, the official national practice guidelines recommend a treatment duration of six months, consistent with WHO guidelines. A Maghrebian recommendation published in 2015, considering the high incidence of Mycobacterium Bovis among cattle and the high consumption of raw milk products, suggested that the treatment duration could be extended to 12 months. It also recommended a prolonged prescription of ethambutol from 1 to 4 months following the initial four-drug regimen for patients with persistent tuberculous lymphadenitis after initial surgery, as Mycobacterium Bovis is naturally resistant to pyrazinamide. 28 Mycobacterium Bovis , present in unpasteurized milk and dairy products, is thought to reach the superior and anterior cervical lymph nodes through micro-ulcerations in the buccal mucosa. 16 , 17 In their Tunisian series, Ghariani et al. identified Mycobacterium Bovis as the strain responsible for tuberculous lymphadenopathy in 76% of bacteriologically diagnosed cases (79 cases). 13 However, while the prevalence of Mycobacterium Bovis infection is likely high, the exact rate remains unknown in Tunisia. Improving molecular diagnostic tools would likely resolve this issue. The control of bovine tuberculosis, which is endemic in Tunisia, is crucial to reducing the incidence of human tuberculous lymphadenitis secondary to Mycobacterium Bovis strains. 16 Statistical analysis In our study, neither age nor gender was predictive of any particular outcome. Similarly, comorbidities did not appear to influence the progression of the disease. Seok et al. reported a significant correlation between younger age and residual lymph node enlargement (defined as lymphadenopathy greater than 10 mm in diameter with enhancement patterns of tuberculosis after six months of treatment). 27 Furthermore, no significant association was found between the initial size of the lymph node and disease progression. This contrasts with the literature, which associates a size greater than 3 cm with unfavorable outcomes. 29 – 31 This discrepancy could be explained by measurement errors or sampling issues. An initial lymph node larger than 3 cm may not be associated with poor progression if it was surgically removed during the initial diagnostic procedure. Pathological skin changes were associated with an unfavorable progression. In contrast, Soriano et al. found that skin changes did not influence prognosis. 26 Regarding radiological data, our study revealed that necrosis on CT scans increased the risk of unfavorable disease outcomes. Zhang et al. also found that a larger area of necrosis was associated with a higher likelihood of poor treatment prognosis. They suggested that necrosis reflects high bacterial virulence, weak immunity, or severe allergic responses, and that its increase is associated with poor response to drug therapy. 32 A statistically significant correlation was observed between surgical drainage of a cold abscess and unfavorable disease progression. This could be explained by the fact that cold abscesses may form distally from the original persistent lymphadenopathy. However, initial neck dissection was associated with a favorable outcome. Liu et al. suggested that surgical removal of cervical lymph node tuberculosis could shorten the time for anti-tuberculosis drug treatment. 33 Tahiri et al. found that biopsy with subtotal excision was associated with an unfavorable outcome. 34 Surgical treatment remains debated in tuberculous lymphadenopathy. Although often difficult and risky, many studies support the theory that surgical treatment should be combined with medical treatment to manage lymph node tuberculosis. 30 , 33 , 34 Lekhbal et al. reported an association between lymphadenopathy greater than or equal to 3 cm and the need for surgery in the treatment of cervical lymph node tuberculosis. 29 Further studies are needed to evaluate the effectiveness of surgical treatment and establish standardized surgical protocols for lymph node tuberculosis. Prolonged ethambutol therapy beyond the first two months was statistically significantly associated with a favorable disease outcome. This supports the hypothesis that Mycobacterium Bovis strains are frequently involved in tuberculous lymphadenopathy in Tunisia. 13 , 16 In our study, improvement at the end of the second month of treatment was significantly associated with a favorable progression. The two-month evaluation may predict the overall outcome and help clinicians manage the disease by conducting further investigations or modifying the therapeutic approach. Limitations The main limitation of the present study was its retrospective design. Additionally, the study was conducted during the COVID-19 pandemic, which led to the postponement or omission of many complementary exams. Furthermore, our study was based on a sample that may not be representative of the entire population affected by cervical lymph node tuberculosis, especially since HIV-positive patients are followed in another department. Both microbiological and molecular diagnoses were insufficient. The surgical procedures performed for initial diagnosis were not uniform across all patients, making it difficult to compare outcomes. In our study, a 9-month period was used to define the outcome; however, in most published studies focusing on outcomes, this period was set at 6 months. Conclusion In our study, lymph node dissection and prolonged ethambutol therapy were the main factors associated with favorable outcomes. Our findings underscore the crucial role of surgery in managing lymph node tuberculosis and highlight the importance of considering regional epidemiological factors of tuberculosis when bacteriological or molecular diagnosis is unavailable. Nevertheless, the small sample size and the low rate of bacteriological confirmation limit the generalizability of our results. Further research is needed to enhance our understanding of lymph node tuberculosis and to better standardize both medical and surgical treatments, particularly in countries where bovine tuberculosis is endemic. Ethical approval: Haut du formulaire This study was approved by the Ethics Committee of Rabta Hospital (Approval number: CERB 04/2025, approved on February 25, 2025). Given the retrospective and descriptive nature of the study, informed consent from participants was not required, as per the ethics committee’s approval. All data were fully anonymized prior to analysis to ensure confidentiality, in compliance with ethical standards, and in adherence to the Declaration of Helsinki. Data availability Zenodo: Factors Predicting Outcome in Cervical Lymph Node Tuberculosis: Insights from a Tunisian Case Series, https://doi.org/10.5281/zenodo.15351592 35 This project contains the following underlying data: Data file 1. Study Database.sav Data file 2. Table -1-.pdf . The data is available under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 International (CC BY-NC-ND 4.0) license. Table 1: Univariate analysis of factors influencing the outcome. Table 1 is available as extended data on Zenodo at https://zenodo.org/records/15351592 . DOI: 10.5281/zenodo.15351592 References 1. Global Tuberculosis Report 2024. Geneva: World Health Organization; 1st ed.2024; 1. 2. Assefa W, Eshete T, Solomon Y, et al. : Clinicoepidemiologic considerations in the diagnosis of tuberculous lymphadenitis: evidence from a high burden country. Int. J. Infect Dis. Nov 2022; 124 : 152–156. 3. 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Lajhouri M: Factors Predicting Outcome in Cervical Lymph Node Tuberculosis: Insights from a Tunisian Case Series. Zenodo. 2025. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 21 May 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia Maissa Lajhouri Roles: Conceptualization, Methodology, Writing – Review & Editing Selima Jouini Roles: Writing – Original Draft Preparation Yosra Ammar Mnejja Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation Azza Mediouni Roles: Validation Rihab Lahmar Roles: Validation Houda Chahed Roles: Validation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 30 Sep 2025, 14:511 https://doi.org/10.12688/f1000research.164097.2 version 1 Published: 21 May 2025, 14:511 https://doi.org/10.12688/f1000research.164097.1 Copyright © 2025 Lajhouri M et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Lajhouri M, Jouini S, Ammar Mnejja Y et al. Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.12688/f1000research.164097.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 30 Sep 2025 Revised Views 0 Cite How to cite this report: Chowdhury MJ and Chowdhury Lt. Col. MMHCLC. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.188524.r419255 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v2#referee-response-419255 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 01 Oct 2025 Ma Jalil Chowdhury , Combined Military Hospital, Ramu Cantonment, Bangladesh M Mainul Hasan Chowdhury Lt. Col. Chowdhury Lt. Col. , CMH, Dhaka, Bangladesh, Dhaka, Dhaka, Bangladesh Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.188524.r419255 Study design: Diagnosing of tuberculous lymphadenitis based only on histopathological findings may create diagnostic dilemma particularly when the full findings are not visible in the report. The author here in this paper did not mention on what histopathological findings the ... Continue reading READ ALL Study design: Diagnosing of tuberculous lymphadenitis based only on histopathological findings may create diagnostic dilemma particularly when the full findings are not visible in the report. The author here in this paper did not mention on what histopathological findings the diagnoses were made. Evaluation: Evaluation depending upon duration of treatment is often misnomer because of the fact that often the concerned physician for lymph node tuberculosis extends the duration of treatment on empirical basis. Evaluation on the size of lymph node is again misnomer. Because non-regression of the size doesn’t always mean non responding. In case of lymph node tuberculosis, the size may not decrease even may increase during or even at the end of treatment because of paradoxical reaction (PR) which is peculiar to anti-TB therapy in lymph node TB. Extending the duration of treatment beyond 6 months solely depending on non-regression or increase in the size of lymph node is not justifiable. Recurrence or resistant TB should not be based on repeat histopathological findings but should be based only on findings of Mycobacterial tuberculosis on culture and even NOT GeneXpert. Because GeneXpert may be positive on dead bacilli. Conventional histopathological findings may persist even after completion of 6- month ant-TB therapy because of delayed hypersensitivity reaction against tuberculo-protein of dead bacilli. Results and Discussion: There should have been scope for diagnosing Bovin TB Lymphadenitis in those who consumed raw milk. Otherwise, the data regarding consumption of raw milk is not useful. It is not understood whether the cutaneous sinus tract was present following doing FNAC which is quit common phenomenon. FNAC was performed in 85 patients. How others were diagnosed? Epithelioid granuloma with necrosis was observed in 33 patients. How others were diagnosed? Microbiological testing was done in 21 patents i.e. 20.6 %; the question is how the percentage was calculated? However, this is meagre for a scientific presentation. Molecular testing was carried out in 21 patients. The question is which 21? Finally, what were the basis of diagnosis of tuberculous lymphadenitis in the case series? If it is solely based on histopathological examination, it will be questionable. Intermediate resistance to rifampicin was found in 7 patients; so, question is how they were treated and what was their outcome? Was microbiological testing done on surgical samples? What was the basis of second-line antituberculosis drugs in 11 patients? Tuberculous recurrence was observed in 12 patients? How the recurrence was diagnosed? Without microbiological testing, it will not be acceptable. Prolonged ethambutol therapy hypothetically thinking of bovine tuberculosis without confirmation may give wrong information to the reader. Intact skin cannot be considered as indicator for favourable outcome. Because deep seated lymph node may lead to formation of sterile abscess in future because of inadequate drainage and may give rise to recurrences and may need adequate surgical clearance. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Chowdhury MJ and Chowdhury Lt. Col. MMHCLC. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.188524.r419255 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v2#referee-response-419255 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 14 Oct 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 14 Oct 2025 Author Response Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on ... Continue reading Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on histopathology when epithelioid and giant cell granulomas with caseous necrosis were observed -When bacteriological confirmation is not possible, the diagnosis of recurrence is primarily based on clinical features (lymph node enlargement and symptoms suggestive of active tuberculosis) and radiological findings, and is supported by histopathology (to also rule out differential diagnoses) or molecular biology. We fully agree that positive histopathology or PCR results may sometimes reflect only a “scar” or a “hallmark” of a previous tuberculous infection. -Regarding treatment duration, this remains a challenging issue. Some authors suggest that lymphadenopathy smaller than one centimeter may justify treatment interruption; however, in most cases, the lymph node remains larger at the end of treatment. Therefore, the decision to stop antituberculous therapy can be difficult when lymphadenopathies persist, particularly if radiologic features suggest active tuberculosis (such as necrosis) and calcifications indicative of 'healed tuberculosis' are absent. -In patients with intermediate resistance to rifampicin, no unfavorable outcomes were observed in our series. -We acknowledge that the lack of bacteriological results is a limitation of our study. Finally, we are pleased that our study has stimulated reflection on the management of tuberculous lymphadenopathies. We sincerely thank you again for your careful review and valuable feedback. Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on histopathology when epithelioid and giant cell granulomas with caseous necrosis were observed -When bacteriological confirmation is not possible, the diagnosis of recurrence is primarily based on clinical features (lymph node enlargement and symptoms suggestive of active tuberculosis) and radiological findings, and is supported by histopathology (to also rule out differential diagnoses) or molecular biology. We fully agree that positive histopathology or PCR results may sometimes reflect only a “scar” or a “hallmark” of a previous tuberculous infection. -Regarding treatment duration, this remains a challenging issue. Some authors suggest that lymphadenopathy smaller than one centimeter may justify treatment interruption; however, in most cases, the lymph node remains larger at the end of treatment. Therefore, the decision to stop antituberculous therapy can be difficult when lymphadenopathies persist, particularly if radiologic features suggest active tuberculosis (such as necrosis) and calcifications indicative of 'healed tuberculosis' are absent. -In patients with intermediate resistance to rifampicin, no unfavorable outcomes were observed in our series. -We acknowledge that the lack of bacteriological results is a limitation of our study. Finally, we are pleased that our study has stimulated reflection on the management of tuberculous lymphadenopathies. We sincerely thank you again for your careful review and valuable feedback. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 14 Oct 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 14 Oct 2025 Author Response Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on ... Continue reading Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on histopathology when epithelioid and giant cell granulomas with caseous necrosis were observed -When bacteriological confirmation is not possible, the diagnosis of recurrence is primarily based on clinical features (lymph node enlargement and symptoms suggestive of active tuberculosis) and radiological findings, and is supported by histopathology (to also rule out differential diagnoses) or molecular biology. We fully agree that positive histopathology or PCR results may sometimes reflect only a “scar” or a “hallmark” of a previous tuberculous infection. -Regarding treatment duration, this remains a challenging issue. Some authors suggest that lymphadenopathy smaller than one centimeter may justify treatment interruption; however, in most cases, the lymph node remains larger at the end of treatment. Therefore, the decision to stop antituberculous therapy can be difficult when lymphadenopathies persist, particularly if radiologic features suggest active tuberculosis (such as necrosis) and calcifications indicative of 'healed tuberculosis' are absent. -In patients with intermediate resistance to rifampicin, no unfavorable outcomes were observed in our series. -We acknowledge that the lack of bacteriological results is a limitation of our study. Finally, we are pleased that our study has stimulated reflection on the management of tuberculous lymphadenopathies. We sincerely thank you again for your careful review and valuable feedback. Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on histopathology when epithelioid and giant cell granulomas with caseous necrosis were observed -When bacteriological confirmation is not possible, the diagnosis of recurrence is primarily based on clinical features (lymph node enlargement and symptoms suggestive of active tuberculosis) and radiological findings, and is supported by histopathology (to also rule out differential diagnoses) or molecular biology. We fully agree that positive histopathology or PCR results may sometimes reflect only a “scar” or a “hallmark” of a previous tuberculous infection. -Regarding treatment duration, this remains a challenging issue. Some authors suggest that lymphadenopathy smaller than one centimeter may justify treatment interruption; however, in most cases, the lymph node remains larger at the end of treatment. Therefore, the decision to stop antituberculous therapy can be difficult when lymphadenopathies persist, particularly if radiologic features suggest active tuberculosis (such as necrosis) and calcifications indicative of 'healed tuberculosis' are absent. -In patients with intermediate resistance to rifampicin, no unfavorable outcomes were observed in our series. -We acknowledge that the lack of bacteriological results is a limitation of our study. Finally, we are pleased that our study has stimulated reflection on the management of tuberculous lymphadenopathies. We sincerely thank you again for your careful review and valuable feedback. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 21 May 2025 Views 0 Cite How to cite this report: Zaheer S. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r406892 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-406892 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 17 Sep 2025 Sufian Zaheer , Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.180548.r406892 Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. 1. Kumari A, et al 2023 [Ref 1] ... Continue reading READ ALL Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. 1. Kumari A, et al 2023 [Ref 1] 2. Ahuja S, et al., 2024 [Ref 2] 3. Ahuja S, et al., 2024 [Ref 3] Introduction -- Could include a more detailed review of previous Tunisian data for comparison. Mateial and results: -- why Microbiological confirmation performed in few cases (20.6%). --- Why were HIV-positive cases excluded -- Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. --- Small sample size and low bacteriological confirmation limit generalizability. Discussion Please discuss latest research in the field including as suggested Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Kumari A, Ahuja S, Bajaj S, Zaheer S, et al.: Cytomorphological findings in drug defaulters of tuberculous lymphadenitis. Cytojournal . 2023; 20 . Publisher Full Text 2. Ahuja S, Malik S, Zaheer S: Tuberculous parotitis: A case series diagnosed on fine needle aspiration. IDCases . 2024; 38 . Publisher Full Text 3. Ahuja S, Behera R, Kumari A, Zaheer S: Cytomorphological findings in confirmed cases of tubercular lymphadenitis. Cytojournal . 2024; 21 . Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Cytopathological aspect of infectious disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Zaheer S. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r406892 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-406892 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Reviewer Response 30 Sep 2025 Sufian Zaheer , Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India 30 Sep 2025 Reviewer Response My concerns are not met in the article Competing Interests: Nil My concerns are not met in the article My concerns are not met in the article Competing Interests: Nil Close Report a concern Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 30 Sep 2025 Author Response Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in ... Continue reading Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. Kumari A, et al 2023 [Ref 1] Ahuja S, et al., 2024 [Ref 2] Ahuja S, et al., 2024 [Ref 3] Response: We have elaborated on the cytopathological findings in the Results section and provided a table summarizing the different patterns observed. Additionally, the suggested references regarding cytopathology in tuberculosis have been reviewed and incorporated into the Discussion section. Comment 2: Introduction – Could include a more detailed review of previous Tunisian data for comparison. Response: Thank you for your valuable comment. We have expanded the Introduction to include a more detailed review of available data on lymph node tuberculosis in Tunisia. Your comment also allowed us to correct an error in a sentence reporting tuberculosis incidence (in the Discussion section) : Tunisia is a country with intermediate tuberculosis incidence, ranging from 50 to 99 cases per 100,000 population per year, according to the 2023 WHO Report. Comment 3: Material and results – Why was microbiological confirmation performed in only a few cases (20.6%)? Response: Microbiological confirmation was performed in only 20.6% of cases, as these were the only results available in the patients’ records. Moreover, in most cases, only cytological examination was performed after fine-needle aspiration, and the aspirated material, including rinse fluid, was not routinely sent for bacteriological testing. Molecular testing was also rarely performed, likely due to the inconsistent availability of PCR kits during the study period. Comment 4: Why were HIV-positive cases excluded? Response: HIV-positive patients were not intentionally excluded; they are routinely followed up in a separate department (Department of Infectious Diseases) at our institution. Tunisia has a low HIV incidence according to the WHO, although it has increased in recent years. To address this point, we added a statement in the Discussion section recommending HIV testing in cases of tuberculous lymphadenitis, particularly in patients with unfavorable outcomes. Comment 5: Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. Response: Although WHO and other expert society guidelines recommend a 6-month regimen, a 9-month treatment course is still commonly adopted by some practitioners for tuberculous lymphadenitis. This approach is justified by the persistence of large lymph nodes after 6 months, likely due to limited drug penetration. Because of the retrospective nature of our study, we considered both 6- and 9-month treatment durations when defining favorable outcomes. Comment 7: Small sample size and low bacteriological confirmation limit generalizability. Response: We have added a statement in the Conclusion section acknowledging that the small sample size and low rate of bacteriological confirmation limit the generalizability of our findings. Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. Kumari A, et al 2023 [Ref 1] Ahuja S, et al., 2024 [Ref 2] Ahuja S, et al., 2024 [Ref 3] Response: We have elaborated on the cytopathological findings in the Results section and provided a table summarizing the different patterns observed. Additionally, the suggested references regarding cytopathology in tuberculosis have been reviewed and incorporated into the Discussion section. Comment 2: Introduction – Could include a more detailed review of previous Tunisian data for comparison. Response: Thank you for your valuable comment. We have expanded the Introduction to include a more detailed review of available data on lymph node tuberculosis in Tunisia. Your comment also allowed us to correct an error in a sentence reporting tuberculosis incidence (in the Discussion section) : Tunisia is a country with intermediate tuberculosis incidence, ranging from 50 to 99 cases per 100,000 population per year, according to the 2023 WHO Report. Comment 3: Material and results – Why was microbiological confirmation performed in only a few cases (20.6%)? Response: Microbiological confirmation was performed in only 20.6% of cases, as these were the only results available in the patients’ records. Moreover, in most cases, only cytological examination was performed after fine-needle aspiration, and the aspirated material, including rinse fluid, was not routinely sent for bacteriological testing. Molecular testing was also rarely performed, likely due to the inconsistent availability of PCR kits during the study period. Comment 4: Why were HIV-positive cases excluded? Response: HIV-positive patients were not intentionally excluded; they are routinely followed up in a separate department (Department of Infectious Diseases) at our institution. Tunisia has a low HIV incidence according to the WHO, although it has increased in recent years. To address this point, we added a statement in the Discussion section recommending HIV testing in cases of tuberculous lymphadenitis, particularly in patients with unfavorable outcomes. Comment 5: Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. Response: Although WHO and other expert society guidelines recommend a 6-month regimen, a 9-month treatment course is still commonly adopted by some practitioners for tuberculous lymphadenitis. This approach is justified by the persistence of large lymph nodes after 6 months, likely due to limited drug penetration. Because of the retrospective nature of our study, we considered both 6- and 9-month treatment durations when defining favorable outcomes. Comment 7: Small sample size and low bacteriological confirmation limit generalizability. Response: We have added a statement in the Conclusion section acknowledging that the small sample size and low rate of bacteriological confirmation limit the generalizability of our findings. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Reviewer Response 30 Sep 2025 Sufian Zaheer , Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India 30 Sep 2025 Reviewer Response My concerns are not met in the article Competing Interests: Nil My concerns are not met in the article My concerns are not met in the article Competing Interests: Nil Close Report a concern Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 30 Sep 2025 Author Response Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in ... Continue reading Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. Kumari A, et al 2023 [Ref 1] Ahuja S, et al., 2024 [Ref 2] Ahuja S, et al., 2024 [Ref 3] Response: We have elaborated on the cytopathological findings in the Results section and provided a table summarizing the different patterns observed. Additionally, the suggested references regarding cytopathology in tuberculosis have been reviewed and incorporated into the Discussion section. Comment 2: Introduction – Could include a more detailed review of previous Tunisian data for comparison. Response: Thank you for your valuable comment. We have expanded the Introduction to include a more detailed review of available data on lymph node tuberculosis in Tunisia. Your comment also allowed us to correct an error in a sentence reporting tuberculosis incidence (in the Discussion section) : Tunisia is a country with intermediate tuberculosis incidence, ranging from 50 to 99 cases per 100,000 population per year, according to the 2023 WHO Report. Comment 3: Material and results – Why was microbiological confirmation performed in only a few cases (20.6%)? Response: Microbiological confirmation was performed in only 20.6% of cases, as these were the only results available in the patients’ records. Moreover, in most cases, only cytological examination was performed after fine-needle aspiration, and the aspirated material, including rinse fluid, was not routinely sent for bacteriological testing. Molecular testing was also rarely performed, likely due to the inconsistent availability of PCR kits during the study period. Comment 4: Why were HIV-positive cases excluded? Response: HIV-positive patients were not intentionally excluded; they are routinely followed up in a separate department (Department of Infectious Diseases) at our institution. Tunisia has a low HIV incidence according to the WHO, although it has increased in recent years. To address this point, we added a statement in the Discussion section recommending HIV testing in cases of tuberculous lymphadenitis, particularly in patients with unfavorable outcomes. Comment 5: Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. Response: Although WHO and other expert society guidelines recommend a 6-month regimen, a 9-month treatment course is still commonly adopted by some practitioners for tuberculous lymphadenitis. This approach is justified by the persistence of large lymph nodes after 6 months, likely due to limited drug penetration. Because of the retrospective nature of our study, we considered both 6- and 9-month treatment durations when defining favorable outcomes. Comment 7: Small sample size and low bacteriological confirmation limit generalizability. Response: We have added a statement in the Conclusion section acknowledging that the small sample size and low rate of bacteriological confirmation limit the generalizability of our findings. Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. Kumari A, et al 2023 [Ref 1] Ahuja S, et al., 2024 [Ref 2] Ahuja S, et al., 2024 [Ref 3] Response: We have elaborated on the cytopathological findings in the Results section and provided a table summarizing the different patterns observed. Additionally, the suggested references regarding cytopathology in tuberculosis have been reviewed and incorporated into the Discussion section. Comment 2: Introduction – Could include a more detailed review of previous Tunisian data for comparison. Response: Thank you for your valuable comment. We have expanded the Introduction to include a more detailed review of available data on lymph node tuberculosis in Tunisia. Your comment also allowed us to correct an error in a sentence reporting tuberculosis incidence (in the Discussion section) : Tunisia is a country with intermediate tuberculosis incidence, ranging from 50 to 99 cases per 100,000 population per year, according to the 2023 WHO Report. Comment 3: Material and results – Why was microbiological confirmation performed in only a few cases (20.6%)? Response: Microbiological confirmation was performed in only 20.6% of cases, as these were the only results available in the patients’ records. Moreover, in most cases, only cytological examination was performed after fine-needle aspiration, and the aspirated material, including rinse fluid, was not routinely sent for bacteriological testing. Molecular testing was also rarely performed, likely due to the inconsistent availability of PCR kits during the study period. Comment 4: Why were HIV-positive cases excluded? Response: HIV-positive patients were not intentionally excluded; they are routinely followed up in a separate department (Department of Infectious Diseases) at our institution. Tunisia has a low HIV incidence according to the WHO, although it has increased in recent years. To address this point, we added a statement in the Discussion section recommending HIV testing in cases of tuberculous lymphadenitis, particularly in patients with unfavorable outcomes. Comment 5: Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. Response: Although WHO and other expert society guidelines recommend a 6-month regimen, a 9-month treatment course is still commonly adopted by some practitioners for tuberculous lymphadenitis. This approach is justified by the persistence of large lymph nodes after 6 months, likely due to limited drug penetration. Because of the retrospective nature of our study, we considered both 6- and 9-month treatment durations when defining favorable outcomes. Comment 7: Small sample size and low bacteriological confirmation limit generalizability. Response: We have added a statement in the Conclusion section acknowledging that the small sample size and low rate of bacteriological confirmation limit the generalizability of our findings. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Gupta VB. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r399070 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-399070 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Sep 2025 Vatsal Bhushan Gupta , Pulmonary Medicine, City Superspeciality hospital, Gorakhpur, Uttar Pradesh, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.180548.r399070 Overall well written. The topic has been described in detail as there are lot of grey areas in management of cervical lymph node TB. Certain queries which need to be resolved. 1. Labelling of figure 1 2. ... Continue reading READ ALL Overall well written. The topic has been described in detail as there are lot of grey areas in management of cervical lymph node TB. Certain queries which need to be resolved. 1. Labelling of figure 1 2. Current treatment of DSTB is 2 months of HRZE and 4 months of HRE. Why was ethambutol given only for 2 months in most cases 3. Do you conclude that surgical treatment should be carried out in all cases of lymph node TB as some cases may be managed by medical therapy once the diagnosis is confirmed Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: COPD, ILD, sleep disorder I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Gupta VB. Reviewer Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r399070 ) The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-399070 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 30 Sep 2025 Author Response Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and ... Continue reading Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and 4 months of HR. Why was ethambutol given only for 2 months in most cases? Response: According to WHO guidelines and official Tunisian recommendations, the standard regimen for drug-susceptible tuberculosis consists of 2 months of HRZE followed by 4 months of HR. A Maghrebian recommendation published in 2015, taking into account the high prevalence of M. bovis , suggests 2 months of HRZE followed by 4 months of HR, with ethambutol optionally extended for 1 to 4 additional months beyond the initial 2 months if clinically indicated. This approach was applied in our series based on local practice patterns and patient-specific considerations. Comment 3: Do you conclude that surgical treatment should be carried out in all cases of lymph node TB, as some cases may be managed by medical therapy once the diagnosis is confirmed? Response: We do not recommend systematic surgical treatment for lymph node tuberculosis. The decision for surgery should be made on a case-by-case basis. When lymph nodes are small, multiple, or bilateral, surgery should generally not be part of first-line management. A 2-month treatment evaluation is particularly helpful to assess response and guide the need for surgery. Surgery may be proposed in cases showing no improvement or enlargement of lymphadenopathies despite adequate medical therapy. When surgery is performed, it is preferable to remove the maximum number of affected lymph nodes safely, while carefully considering the risk of adhesions. Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and 4 months of HR. Why was ethambutol given only for 2 months in most cases? Response: According to WHO guidelines and official Tunisian recommendations, the standard regimen for drug-susceptible tuberculosis consists of 2 months of HRZE followed by 4 months of HR. A Maghrebian recommendation published in 2015, taking into account the high prevalence of M. bovis , suggests 2 months of HRZE followed by 4 months of HR, with ethambutol optionally extended for 1 to 4 additional months beyond the initial 2 months if clinically indicated. This approach was applied in our series based on local practice patterns and patient-specific considerations. Comment 3: Do you conclude that surgical treatment should be carried out in all cases of lymph node TB, as some cases may be managed by medical therapy once the diagnosis is confirmed? Response: We do not recommend systematic surgical treatment for lymph node tuberculosis. The decision for surgery should be made on a case-by-case basis. When lymph nodes are small, multiple, or bilateral, surgery should generally not be part of first-line management. A 2-month treatment evaluation is particularly helpful to assess response and guide the need for surgery. Surgery may be proposed in cases showing no improvement or enlargement of lymphadenopathies despite adequate medical therapy. When surgery is performed, it is preferable to remove the maximum number of affected lymph nodes safely, while carefully considering the risk of adhesions. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia 30 Sep 2025 Author Response Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and ... Continue reading Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and 4 months of HR. Why was ethambutol given only for 2 months in most cases? Response: According to WHO guidelines and official Tunisian recommendations, the standard regimen for drug-susceptible tuberculosis consists of 2 months of HRZE followed by 4 months of HR. A Maghrebian recommendation published in 2015, taking into account the high prevalence of M. bovis , suggests 2 months of HRZE followed by 4 months of HR, with ethambutol optionally extended for 1 to 4 additional months beyond the initial 2 months if clinically indicated. This approach was applied in our series based on local practice patterns and patient-specific considerations. Comment 3: Do you conclude that surgical treatment should be carried out in all cases of lymph node TB, as some cases may be managed by medical therapy once the diagnosis is confirmed? Response: We do not recommend systematic surgical treatment for lymph node tuberculosis. The decision for surgery should be made on a case-by-case basis. When lymph nodes are small, multiple, or bilateral, surgery should generally not be part of first-line management. A 2-month treatment evaluation is particularly helpful to assess response and guide the need for surgery. Surgery may be proposed in cases showing no improvement or enlargement of lymphadenopathies despite adequate medical therapy. When surgery is performed, it is preferable to remove the maximum number of affected lymph nodes safely, while carefully considering the risk of adhesions. Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and 4 months of HR. Why was ethambutol given only for 2 months in most cases? Response: According to WHO guidelines and official Tunisian recommendations, the standard regimen for drug-susceptible tuberculosis consists of 2 months of HRZE followed by 4 months of HR. A Maghrebian recommendation published in 2015, taking into account the high prevalence of M. bovis , suggests 2 months of HRZE followed by 4 months of HR, with ethambutol optionally extended for 1 to 4 additional months beyond the initial 2 months if clinically indicated. This approach was applied in our series based on local practice patterns and patient-specific considerations. Comment 3: Do you conclude that surgical treatment should be carried out in all cases of lymph node TB, as some cases may be managed by medical therapy once the diagnosis is confirmed? Response: We do not recommend systematic surgical treatment for lymph node tuberculosis. The decision for surgery should be made on a case-by-case basis. When lymph nodes are small, multiple, or bilateral, surgery should generally not be part of first-line management. A 2-month treatment evaluation is particularly helpful to assess response and guide the need for surgery. Surgery may be proposed in cases showing no improvement or enlargement of lymphadenopathies despite adequate medical therapy. When surgery is performed, it is preferable to remove the maximum number of affected lymph nodes safely, while carefully considering the risk of adhesions. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 21 May 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 30 Sep 25 read Version 1 21 May 25 read read Vatsal Bhushan Gupta , City Superspeciality hospital, Gorakhpur, India Sufian Zaheer , Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India Ma Jalil Chowdhury , Combined Military Hospital, Ramu Cantonment, Bangladesh M Mainul Hasan Chowdhury Lt. Col. Chowdhury Lt. Col. , CMH, Dhaka, Bangladesh, Dhaka, Bangladesh Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Chowdhury M et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 01 Oct 2025 | for Version 2 Ma Jalil Chowdhury , Combined Military Hospital, Ramu Cantonment, Bangladesh M Mainul Hasan Chowdhury Lt. Col. Chowdhury Lt. Col. , CMH, Dhaka, Bangladesh, Dhaka, Dhaka, Bangladesh 0 Views copyright © 2025 Chowdhury M et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Study design: Diagnosing of tuberculous lymphadenitis based only on histopathological findings may create diagnostic dilemma particularly when the full findings are not visible in the report. The author here in this paper did not mention on what histopathological findings the diagnoses were made. Evaluation: Evaluation depending upon duration of treatment is often misnomer because of the fact that often the concerned physician for lymph node tuberculosis extends the duration of treatment on empirical basis. Evaluation on the size of lymph node is again misnomer. Because non-regression of the size doesn’t always mean non responding. In case of lymph node tuberculosis, the size may not decrease even may increase during or even at the end of treatment because of paradoxical reaction (PR) which is peculiar to anti-TB therapy in lymph node TB. Extending the duration of treatment beyond 6 months solely depending on non-regression or increase in the size of lymph node is not justifiable. Recurrence or resistant TB should not be based on repeat histopathological findings but should be based only on findings of Mycobacterial tuberculosis on culture and even NOT GeneXpert. Because GeneXpert may be positive on dead bacilli. Conventional histopathological findings may persist even after completion of 6- month ant-TB therapy because of delayed hypersensitivity reaction against tuberculo-protein of dead bacilli. Results and Discussion: There should have been scope for diagnosing Bovin TB Lymphadenitis in those who consumed raw milk. Otherwise, the data regarding consumption of raw milk is not useful. It is not understood whether the cutaneous sinus tract was present following doing FNAC which is quit common phenomenon. FNAC was performed in 85 patients. How others were diagnosed? Epithelioid granuloma with necrosis was observed in 33 patients. How others were diagnosed? Microbiological testing was done in 21 patents i.e. 20.6 %; the question is how the percentage was calculated? However, this is meagre for a scientific presentation. Molecular testing was carried out in 21 patients. The question is which 21? Finally, what were the basis of diagnosis of tuberculous lymphadenitis in the case series? If it is solely based on histopathological examination, it will be questionable. Intermediate resistance to rifampicin was found in 7 patients; so, question is how they were treated and what was their outcome? Was microbiological testing done on surgical samples? What was the basis of second-line antituberculosis drugs in 11 patients? Tuberculous recurrence was observed in 12 patients? How the recurrence was diagnosed? Without microbiological testing, it will not be acceptable. Prolonged ethambutol therapy hypothetically thinking of bovine tuberculosis without confirmation may give wrong information to the reader. Intact skin cannot be considered as indicator for favourable outcome. Because deep seated lymph node may lead to formation of sterile abscess in future because of inadequate drainage and may give rise to recurrences and may need adequate surgical clearance. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 14 Oct 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia Dear Reviewer, Thank you very much for your valuable and thoughtful comments. We would like to kindly clarify the following points: -The diagnosis of tuberculosis was made based on histopathology when epithelioid and giant cell granulomas with caseous necrosis were observed -When bacteriological confirmation is not possible, the diagnosis of recurrence is primarily based on clinical features (lymph node enlargement and symptoms suggestive of active tuberculosis) and radiological findings, and is supported by histopathology (to also rule out differential diagnoses) or molecular biology. We fully agree that positive histopathology or PCR results may sometimes reflect only a “scar” or a “hallmark” of a previous tuberculous infection. -Regarding treatment duration, this remains a challenging issue. Some authors suggest that lymphadenopathy smaller than one centimeter may justify treatment interruption; however, in most cases, the lymph node remains larger at the end of treatment. Therefore, the decision to stop antituberculous therapy can be difficult when lymphadenopathies persist, particularly if radiologic features suggest active tuberculosis (such as necrosis) and calcifications indicative of 'healed tuberculosis' are absent. -In patients with intermediate resistance to rifampicin, no unfavorable outcomes were observed in our series. -We acknowledge that the lack of bacteriological results is a limitation of our study. Finally, we are pleased that our study has stimulated reflection on the management of tuberculous lymphadenopathies. We sincerely thank you again for your careful review and valuable feedback. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Chowdhury MJ and Chowdhury Lt. Col. MMHCLC. Peer Review Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.188524.r419255) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-511/v2#referee-response-419255 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Zaheer S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 17 Sep 2025 | for Version 1 Sufian Zaheer , Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India 0 Views copyright © 2025 Zaheer S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (2) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. 1. Kumari A, et al 2023 [Ref 1] 2. Ahuja S, et al., 2024 [Ref 2] 3. Ahuja S, et al., 2024 [Ref 3] Introduction -- Could include a more detailed review of previous Tunisian data for comparison. Mateial and results: -- why Microbiological confirmation performed in few cases (20.6%). --- Why were HIV-positive cases excluded -- Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. --- Small sample size and low bacteriological confirmation limit generalizability. Discussion Please discuss latest research in the field including as suggested Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes References 1. Kumari A, Ahuja S, Bajaj S, Zaheer S, et al.: Cytomorphological findings in drug defaulters of tuberculous lymphadenitis. Cytojournal . 2023; 20 . Publisher Full Text 2. Ahuja S, Malik S, Zaheer S: Tuberculous parotitis: A case series diagnosed on fine needle aspiration. IDCases . 2024; 38 . Publisher Full Text 3. Ahuja S, Behera R, Kumari A, Zaheer S: Cytomorphological findings in confirmed cases of tubercular lymphadenitis. Cytojournal . 2024; 21 . Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Cytopathological aspect of infectious disease I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (2) Reviewer Response 30 Sep 2025 Sufian Zaheer, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India My concerns are not met in the article View more View less Competing Interests Nil reply Respond Report a concern Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia Comments 1 and 6: Please elaborate cytopathological findings in your results and tabulate it. It will be very helpful. You may use the following articles pertinent to your research in discussion regarding cytopathological findings. Kumari A, et al 2023 [Ref 1] Ahuja S, et al., 2024 [Ref 2] Ahuja S, et al., 2024 [Ref 3] Response: We have elaborated on the cytopathological findings in the Results section and provided a table summarizing the different patterns observed. Additionally, the suggested references regarding cytopathology in tuberculosis have been reviewed and incorporated into the Discussion section. Comment 2: Introduction – Could include a more detailed review of previous Tunisian data for comparison. Response: Thank you for your valuable comment. We have expanded the Introduction to include a more detailed review of available data on lymph node tuberculosis in Tunisia. Your comment also allowed us to correct an error in a sentence reporting tuberculosis incidence (in the Discussion section) : Tunisia is a country with intermediate tuberculosis incidence, ranging from 50 to 99 cases per 100,000 population per year, according to the 2023 WHO Report. Comment 3: Material and results – Why was microbiological confirmation performed in only a few cases (20.6%)? Response: Microbiological confirmation was performed in only 20.6% of cases, as these were the only results available in the patients’ records. Moreover, in most cases, only cytological examination was performed after fine-needle aspiration, and the aspirated material, including rinse fluid, was not routinely sent for bacteriological testing. Molecular testing was also rarely performed, likely due to the inconsistent availability of PCR kits during the study period. Comment 4: Why were HIV-positive cases excluded? Response: HIV-positive patients were not intentionally excluded; they are routinely followed up in a separate department (Department of Infectious Diseases) at our institution. Tunisia has a low HIV incidence according to the WHO, although it has increased in recent years. To address this point, we added a statement in the Discussion section recommending HIV testing in cases of tuberculous lymphadenitis, particularly in patients with unfavorable outcomes. Comment 5: Using 9 months instead of 6 months as cutoff may reduce comparability with other studies. Response: Although WHO and other expert society guidelines recommend a 6-month regimen, a 9-month treatment course is still commonly adopted by some practitioners for tuberculous lymphadenitis. This approach is justified by the persistence of large lymph nodes after 6 months, likely due to limited drug penetration. Because of the retrospective nature of our study, we considered both 6- and 9-month treatment durations when defining favorable outcomes. Comment 7: Small sample size and low bacteriological confirmation limit generalizability. Response: We have added a statement in the Conclusion section acknowledging that the small sample size and low rate of bacteriological confirmation limit the generalizability of our findings. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Zaheer S. Peer Review Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r406892) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-406892 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Gupta V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Sep 2025 | for Version 1 Vatsal Bhushan Gupta , Pulmonary Medicine, City Superspeciality hospital, Gorakhpur, Uttar Pradesh, India 0 Views copyright © 2025 Gupta V. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Overall well written. The topic has been described in detail as there are lot of grey areas in management of cervical lymph node TB. Certain queries which need to be resolved. 1. Labelling of figure 1 2. Current treatment of DSTB is 2 months of HRZE and 4 months of HRE. Why was ethambutol given only for 2 months in most cases 3. Do you conclude that surgical treatment should be carried out in all cases of lymph node TB as some cases may be managed by medical therapy once the diagnosis is confirmed Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise COPD, ILD, sleep disorder I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 30 Sep 2025 Maissa Lajhouri , Department of otorhinolaryngology- Head and Neck Surgery, La Rabta University Hospital Center, Tunis, 1007, Tunisia Comment 1: Labelling of figure 1 Response: We have completed and clarified the labelling of Figure 1. Comment 2: Current treatment of DSTB is 2 months of HRZE and 4 months of HR. Why was ethambutol given only for 2 months in most cases? Response: According to WHO guidelines and official Tunisian recommendations, the standard regimen for drug-susceptible tuberculosis consists of 2 months of HRZE followed by 4 months of HR. A Maghrebian recommendation published in 2015, taking into account the high prevalence of M. bovis , suggests 2 months of HRZE followed by 4 months of HR, with ethambutol optionally extended for 1 to 4 additional months beyond the initial 2 months if clinically indicated. This approach was applied in our series based on local practice patterns and patient-specific considerations. Comment 3: Do you conclude that surgical treatment should be carried out in all cases of lymph node TB, as some cases may be managed by medical therapy once the diagnosis is confirmed? Response: We do not recommend systematic surgical treatment for lymph node tuberculosis. The decision for surgery should be made on a case-by-case basis. When lymph nodes are small, multiple, or bilateral, surgery should generally not be part of first-line management. A 2-month treatment evaluation is particularly helpful to assess response and guide the need for surgery. Surgery may be proposed in cases showing no improvement or enlargement of lymphadenopathies despite adequate medical therapy. When surgery is performed, it is preferable to remove the maximum number of affected lymph nodes safely, while carefully considering the risk of adhesions. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Gupta VB. Peer Review Report For: Factors predicting outcome in cervical lymph node tuberculosis: insights from a Tunisian case series [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 14 :511 ( https://doi.org/10.5256/f1000research.180548.r399070) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-511/v1#referee-response-399070 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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last seen: 2026-05-20T01:45:00.602351+00:00