Vulvovaginal tumors and pseudo-tumors: a clinicopathological analysis of 57 cases.

This is a retrospective study including all consecutive eligible vulvar and vaginal tumors and tumor-like lesions (pseudo-tumors) diagnosed at our Pathology department from February 20, 2020 to April 30, 2024 (a period of approximately 4 years). Clinical and pathological data were extracted from patients’ Pathology request forms and Pathology reports. We have included consecutive eligible cases of vulvar and vaginal tumors and pseudo-tumors (tumor-like lesions) obtained from biopsy or organ-resection specimens. Pseudo-tumors or tumor-like lesions are defined as non-neoplastic mass-forming lesions. They are commonly reactive or malformative lesions that show polyclonality (heterogenous cell populations) on molecular analysis. We have excluded cases of lesions that did not form clinically apparent masses (inflammatory lesions or endometriosis) as they were already clinically and biologically diagnosed before the histopathological analysis. The histopathological diagnosis was performed on formalin-fixed and paraffin-embedded specimens stained by hematoxylin and eosin (H&E). Differences in the distribution of variables between different clinicopathological groups (patient with vulvar lesions versus those with vaginal lesions) were assessed using the Fisher exact test or the chi-square test (for categorical variables) and the Student’s t-test (for continuous variables). Statistical analyses were performed by using SPSS ® 25.0 version software for Windows. Differences are considered statistically significant when p  < 0.05.

During our study-period, we have registered 57 patients with vulvovaginal lesions, after exclusion of 7 cases that presented with non mass-forming lesions (6 patients with non-specific inflammatory lesions and 1 patient with vaginal endometriosis). The mean age was 38.55 years ± 16.65 (range of 5 months and 72 years). The histopathological diagnosis was made on 23 biopsies and 34 resected specimens. On these resected specimens, lesions were mostly cystic (17/30 cases, 56.7%) with a mean size of 3.9 cm ± 2.07 (range of 0.8 and 9 cm). Histopathological classifications of vulvovaginal tumors and pseudo-tumors are presented on Table  1 . There were 34 cases (59.6%) of benign lesions mostly Bartholin cysts (19.3%) (Fig.  1 ), followed by hemangioma, fibroepithelial polyp, condyloma acuminatum (7% each), epidermal cyst (3 cases, 5.3%) and lipoma (2 cases, 3.5%) (Fig.  2 ). The remaining cases were malignant tumors (23 patients, 40.4%). During our study-period we have registered 181 cases of gynecological cancers (23 vulvar and vaginal cancers, 74 uterine cancers and 84 ovarian cancers), with vulvo-vaginal cancers representing 12.7% of all gynecological cancers. Malignant tumors were mostly vaginal metastatic carcinomas (15 cases, 26.3%), followed by SCC (4 cases, 7%) (Fig.  3 ), adenoid cystic carcinoma (3 patients, 5.3%) (Fig.  4 ) and spindle cell rhabdomyosarcoma (1 case, 1.7%) (Fig.  5 ). These metastatic vaginal tumors were from the uterine cervix (7 cases of SCC), uterus (1 case of endometrioid carcinoma), recto-colon (5 cases of adenocarcinoma) and urinary bladder (2 cases of high grade urothelial carcinoma). All cases of metastases presented with concomitant primary tumors and secondary vaginal tumors, with compatible morphology, without immunohistochemical analysis (not available in our Country). Table 1 Histological classification of vulvovaginal tumors and pseudo-tumors Biological behavior Histological types Number Percentage (%) Benign tumors and lesions ( n  = 34; 59.6%) Hemangioma 4 7 Fibroepithelial stromal polyp 4 7 Condyloma 4 7 HSIL (VIN2) 1 1.7 Lipoma 2 3.5 Fibrous hamartoma of infancy 1 1.7 Syringoma 1 1.7 Hidradenoma papilliferum 1 1.7 Neurofibroma 1 1.7 Müllerian cyst 1 1.7 Epidermal cyst 3 5.3 Bartholin cyst 11 19.3 Malignant tumors ( n  = 23; 40.4%) Squamous cell carcinoma 4 7 Adenoid cystic carcinoma 3 5.3 Rhabdomyosarcoma 1 1.7 Metastatic carcinomas 15 26.3 Total 57 100 Histological classification of vulvovaginal tumors and pseudo-tumors Fig. 1 Histological image of a Bartholin cyst, showing cystically dilated glands filled with amorphous eosinophilic material and lined by cuboidal stratified epithelium (hematoxylin & eosin x 100) Histological image of a Bartholin cyst, showing cystically dilated glands filled with amorphous eosinophilic material and lined by cuboidal stratified epithelium (hematoxylin & eosin x 100) Fig. 2 Resected specimen of vulvar lipoma showing a well circumscribed homogenous fatty tumor Resected specimen of vulvar lipoma showing a well circumscribed homogenous fatty tumor Fig. 3 Well differentiated squamous cell carcinoma showing thick trabecular structures made of polygonal atypical cells with abundant eosinophilic cytoplasm with keratinization (hematoxylin & eosin x 200) Well differentiated squamous cell carcinoma showing thick trabecular structures made of polygonal atypical cells with abundant eosinophilic cytoplasm with keratinization (hematoxylin & eosin x 200) Fig. 4 Vulvar adenoid cystic carcinoma. a tumor cells with solid, microcystic and trabecular architecture infiltrating a loose fibrous stroma (hematoxylin & eosin x 100). b tumor cells encircling a nervous structure (hematoxylin & eosin x 400) Vulvar adenoid cystic carcinoma. a tumor cells with solid, microcystic and trabecular architecture infiltrating a loose fibrous stroma (hematoxylin & eosin x 100). b tumor cells encircling a nervous structure (hematoxylin & eosin x 400) Fig. 5 Vaginal spindle cell rhabdomyosarcoma. a clinical image showing a necrotic and hemorrhagic tumor prolapsing into the vulva. b clinical image of the same patient after surgical resection. c histological view showing spindle cells with abundant elongated eosinophilic cytoplasm (rhabdomyoblasts) (hematoxylin & eosin x 400) Vaginal spindle cell rhabdomyosarcoma. a clinical image showing a necrotic and hemorrhagic tumor prolapsing into the vulva. b clinical image of the same patient after surgical resection. c histological view showing spindle cells with abundant elongated eosinophilic cytoplasm (rhabdomyoblasts) (hematoxylin & eosin x 400) The Table  2 summarizes the clinicopathological differences between vulvar (30 cases, 52.6%) and vaginal (27 cases, 47.4%) tumors and pseudo-tumors. Patients with vaginal lesions were older than those with vulvar lesions (respective mean ages of 43.64 years ± 17.58 and 34.01 ± 14.63; p  = 0.034). Vaginal lesions were more frequently found in patients aged ≥ 60 years, whereas vulvar lesions were often present in women aged 30–39 years (Fig.  6 ). The vast majority of vaginal lesions were malignant in contrast to vulvar lesions (70.4% versus 13.4%; p  < 0.001). Epithelial lesions were the most histopathological type in the 2 organs without any statistical significant difference ( p  = 0.212). Table 2 Comparison between vulvar and vaginal lesions Variables Vulvar lesions Vaginal lesions p value Age (years) - Mean ± SD 34.01 ± 14.63 43.64 ± 17.58 0.034 - <50 26 (92.9%) 15 (60%) 0.007 - ≥50 2 (7.1%) 10 (40%) Total = 53 28 (100%) 25 (100%) Lesion’s behavior - Benign 26 (86.7%) 8 (29.6%) 5 8 (36.4%) 0 (0%) Total = 27 22 (100%) 5 (100%) 0.234 0.280 Histological type - Epithelial lesions 21 (70%) 23 (85.2%) - Mesenchymal lesions 9 (30%) 4 (14.8%) Total = 57 30 (100%) 27 (100%) 0.216 Comparison between vulvar and vaginal lesions 0.234 0.280 Fig. 6 Repartition of vulvar and vaginal lesions across ages Repartition of vulvar and vaginal lesions across ages

Vulvovaginal lesions are uncommonly reported masses encompassing a wide variety of histopathological entities. Vulvar lesions are more often benign cystic lesions and occur in younger patients. In contrast, vaginal lesions are frequently malignant metastatic tumors from neighboring organs and found in older women. These clinicopathological features should guide clinicians for adequate patients’ management. More studies with additional cases of vulvovaginal lesions are needed to address the data paucity of this seemingly neglected pathology.

Compared to their uterine and ovarian counterparts, vulvar and vaginal lesions have gained little attention across medical literature [ 7 , 9 , 12 , 16 , 25 ]. They are rarely reported perhaps due to cultural considerations preventing women from seeking appropriate medical attention [ 7 ]. Our current study is a contribution on this seemingly neglected topic [ 9 ], through a retrospective study from a developing country. We found that most tumors and pseudo-tumors were benign (34 patients, 59.6%), but with a significant proportion of cancers (23 cases, 40.4%). Bartholin cysts were the most common benign lesion representing 11/34 cases (32.3%), whereas metastatic carcinomas represented the majority of malignant tumors (15/23 cases, 65.2%). We have registered a wide variety of histopathological entities with epithelial and mesenchymal differentiation, we did not found lymphoid or melanocytic tumors as reported in some previous studies [ 26 – 28 ]. In fact, lymphoid and melanocytic tumors are very rare, epithelial and mesenchymal tumors and pseudo-tumors represent the predominant lesions of the vulva and vagina [ 1 , 5 , 15 ]. We found that the vast majority of vulvar lesions were benign (26/30 cases, 86.7%), predominantly Bartholin gland cysts. In fact Bartholin’s gland is located in the distal part of the vagina in the vulvar vestibule and when affected by diseases patients often present with vaginal bulging masses, that is why clinicians usually classify Bartholin’s gland diseases as vulvar lesions rather than vaginal lesions [ 5 , 6 ]. Bartholin cyst is one of the commonest benign vulvovaginal pseudo-tumor resulting in the obstruction of the gland’s excretory duct leading to inflammation and accumulation of secretions [ 1 – 3 , 11 , 29 ]. On histopathological examination Bartholin cyst appears as a cystically dilated gland lined by benign looking simple cuboidal or stratified epithelium, squamous or transitional metaplasia may also be associated [ 11 ]. Other benign vulvar lesions in our study include condyloma (3/30 cases, 10%), fibroepithelial stromal polyp (3/30 cases, 10%), lipoma (2/30 cases, 6.7%), hemangioma (2/30 cases, 6.7%), epidermal cyst (1/30 cases, 3.3%), syringoma (1/30 cases, 3.3%), hidradenoma papilliferum (1/30 cases, 3.3%), neurofibroma (1/30 cases, 3.3%) and fibrous hamartoma of infancy (1/30 cases, 3.3%). Condyloma acuminata is a frequent vulvar and perineal lesion strongly associated with chronic Human papilloma virus infection and may lead to invasive squamous cell carcinoma [ 20 , 30 – 32 ]. Also, syringoma and hidradenoma papilliferum are adnexal benign tumors that may be found in the vulvar region [ 33 ]. Lipoma is a rare benign mature adipocytic tumor of the vulva usually manifesting as a labia majora enlargement [ 13 , 34 – 36 ]. Among the 30 vulvar lesions in our series, 4 were cancers (13.3%), comprising 3 cases of adenoid cystic carcinoma (ACC) and 1 case of squamous cell carcinoma (SCC). The predominant malignant tumor of the vulva is classically the SCC [ 1 , 5 , 20 , 22 ], we think that the predominance of ACC in our series is more likely due to the small size of our sample. Adenoid cystic carcinoma is a salivary-gland type tumor, but may be seen elsewhere in organs like lacrimal gland, the skin, the breast, or the respiratory tract [ 37 – 39 ]. The involvement of the vulva by ACC is a rare occurrence and Bartholin’s gland is the classic site of this tumor [ 37 , 40 ]. At histopathological examination ACC shows a characteristic cribriform architecture with frequent perineural invasion [ 37 ]. As reported in previous studies, we found that vaginal lesions are often malignant metastatic tumors from nearby organs (cervix, uterus, urinary bladder, recto-colon) [ 17 , 19 ]. In our current study the vast majority of vaginal cancers were metastatic tumors (15/19 cases, 78.9%), the remaining cases were primary vaginal SCC (3 patients, 15.8%) and rhabdomyosarcoma (1 case, 5.3%). Rhabdomyosarcoma is a common pediatric soft tissue tumor involving rarely the lower female genital tract [ 41 ]. Our case of rhabdomyosarcoma was from a 18 year-old patient presenting with a huge necrotic and hemorrhagic mass prolapsing into the vulva. We found that women with vaginal lesions were older than those with vulvar lesions, this is logical because most vaginal lesions were metastatic cancers that usually affect post-menopausal women (uterine, urinary bladder and colo-rectal carcinomas). Our study has a merit to include a wide variety of histopathological vulvar and vaginal tumors and pseudo-tumors. This would allow clinicians and pathologists to be more familiar with the seemingly neglected pathology of the lower female genital organs. However, our study has some limitations such as the single-center and retrospective design, a relatively small sample size, lack of clinical symptoms and treatment data, and the unavailability of ancillary tests (especially immunohistochemistry that is not available in our country). More studies including all the above-mentioned aspects are needed in the future.

The vulva and the vagina are lower female genital organs that can be affected by a variety of diseases ranging from malformations, inflammations, infections, to benign or malignant tumors [ 1 – 6 ]. Despite this rich spectrum of diseases, little attention is given to vulvovaginal pathology in the literature especially when compared to other female genital organs like ovary, uterus and uterine cervix [ 7 – 9 ]. Although rarely reported, the pathology of the vulva and the vagina is very heterogenous [ 1 , 2 ]. A part from inflammatory and infectious diseases, the spectrum of vulvovaginal lesions covers a wide range of masses of diverse histological nature: mesenchymal, lymphoid, melanocytic and epithelial tumors [ 10 – 15 ]. The vulva is mainly affected by benign cystic epithelial lesions (mostly pseudo-tumors), whereas the vagina is usually involved by malignant tumors from nearby organs (the uterine cervix, uterus, urinary bladder or the rectum) or distant organs [ 5 , 16 – 19 ]. Both vulvar and vaginal primary malignant tumors are largely represented by the squamous cell carcinoma (SCC) and its variants [ 8 , 20 ]. These cancers are strongly associated with high-risk Human papilloma virus chronic infection (HPV) with aggressive clinical behavior and are often diagnosed at advanced stages [ 21 , 22 ]. The incidence and mortality from gynecological cancers are high and will continue to rise in the coming years [ 9 , 23 ]. The diagnosis and management of vulvovaginal lesions require a multidisciplinary approach where the Pathologist plays a critical role especially by performing correct diagnoses and lesions’ classifications [ 1 , 5 , 8 , 24 , 25 ]. As widely pointed out, the current literature offers little data about vulvovaginal lesions, thus we herein report our histopathological experience about these neglected lesions in a low-income setting in order to increase awareness of their clinicopathological features.