{"paper_id":"e7df580d-6017-46ad-b84b-6505bccf6cbd","body_text":"Main Article\nBrushing cytology in cutaneous lesions of the\nhead and neck\nDT AMIOLAKIS,EP ROIMOS*, G E PEROGAMVRAKIS*, C E SKOULAKIS†, G C GEORGIOU,CEP APADAKIS*\nAbstract\nBackground: Brushing cytology is a well established diagnostic procedure used by gynaecologists,\nphysicians and surgeons to obtain representative samples from lesions. Our aim was to evaluate its\nreliability in ulcerative and tumour-like conditions arising in the skin of the head and neck.\nMethods: Over 28 months, 86 patients with suspected cutaneous malignant lesions underwent a\ncytological examination with a cytobrush within the otolaryngology department.\nResults: Cytological analysis identified 63 out of 64 histologically documented malignant tumours (60\nprimary basal cell and squamous cell carcinomas and three metastatic adenocarcinomas), and 21 out of\n22 benign lesions. There was one false positive and one false negative result.\nConclusions: Brushing cytology of suspected cutaneous malignant lesions is a rapid and reliable\ndiagnostic method which helps the clinician to decide on appropriate planning and treatment. The\ntechnique can be performed as an out-patient procedure, and smear preparation can be done in\nthe laboratory, even at a peripheral hospital.\nKey words: Cytology; Skin Neoplasms; Head and Neck\nIntroduction\nThere are two absolute indications for pre-operative\ndiagnosis of tumours and tumour-like conditions of\nthe skin, subcutaneous tissue and soft tissues: a\nprimary lesion, and clinical suspicion of a recurrence\nor metastasis. The ‘gold standard’ for diagnosis is\nopen biopsy of the lesion with histological examin-\nation of the excised tissue.\nPre-operative cytological evaluation is not a well\nrecognised modality in this field, yet it offers\nseveral advantages.\n1,2 The aims of cytological evalu-\nation are to establish an aetiological and/or morpho-\nlogical diagnosis and thereby to establish a more\naccurate prognosis. Cytology is a useful tool for\ndifferentiating inflammatory and infectious lesions\nfrom those that are neoplastic. In many cases,\ncytology is also helpful in determining whether a\ntumour is malignant or benign. Cytology does\nhowever have its limitations, and these should be\nrecognised. Problems may arise when an inflamma-\ntory response results in secondary dysplastic\nchanges which can mimic those normally associated\nwith neoplasia. It is also worth noting that, in\npoorly differentiated tumours, cytological examin-\nation may not identify the tissue of origin. Cytology,\ntherefore, should not be regarded as a substitute for\nhistopathological examination of biopsy specimens.\nHistology is more likely to provide a definite\ndiagnosis and, since biopsies preserve tissue architec-\nture, grading and classification of the tumour is\nusually possible.\nCytological examination of skin brushing material\ncan be considered a rapid screening technique and\nmay be used as an adjunct to biopsy. Patient\nanxiety can be relieved by providing an instant diag-\nnosis, followed by discussion of treatment options.\nSurgery can be avoided if the lesion proves to be non-\nneoplastic, or delayed for convenience if it is benign.\nA diagnosis of malignancy allows pre-operative\nstaging and planning of the extent of surgery. In\naddition, some cases may be managed either by\nradiotherapy\n3 or local (intralesional) interferon\ntreatment.4,5 Furthermore, surgery in other cases\nmay cause complications; for example, in older\npatients receiving systemic therapy, and in patients\nwith multiple lesions for which restoration demands\nextensive skin allografting.\nThe most common malignant tumours arising from\na chronic disease background are squamous cell\ncarcinoma (SCC) and basal cell carcinoma (BCC).\nCanti published, in 1979, a study of 1628 BCCs,\nwhich used scraping cytology and obtained very satisfy-\ning diagnostic results.\n6 In contrast, we used brushing\ncytology in our work, using a rapid staining method\nFrom the Departments of Cytopathology and *ENT, Chania General Hospital, Chania, Crete and the †ENT Department, General\nHospital of Volos, Volos, Greece.\nAccepted for publication: 19 April 2006.\nThe Journal of Laryngology & Otology (2007) , 121, 676 – 679.\n# 2007 JLO (1984) Limited\ndoi:10.1017/S0022215107007104\nPrinted in the United Kingdom\nFirst published online 3 April 2007\n676\nhttps://doi.org/10.1017/S0022215107007104 Published online by Cambridge University Press\n\n(one minute duration) which was repeated when\nnecessary, and we found that the sampling inade-\nquacy rate was significantly diminished. This techni-\ncal difference must be stressed; in the 1979 study,\nthe sampling inadequacy rate was high due to\ninadequate exfoliation of cells. Correct smear prep-\naration and proper fixation and staining techniques\nare also essential for optimal diagnostic results.\n7\nOur study investigated the diagnostic accuracy,\nspecificity and sensitivity of brushing cytology in\nhead and neck cutaneous lesions.\nMaterials and methods\nEighty-six patients were examined in the department\nof otolaryngology, head and neck surgery of Chania\nGeneral Hospital, over a 28-month period, and an\nequal number of lesions were documented in the\nfiles of the cytology department.\nIn most cases, clinical examination found an ulcer or\nexophytic mass. In a small number of cases, there was a\nhealing or a flat, red-grey lesion surrounded by a small\nhalo. The lesions were localised on the preauricular\narea (27), the temporal area (26), the lateral aspects\no ft h en e c k( 1 5 ) ,t h eo r b i t( fi v e ) ,t h en o s e( t h r e e ) ,\nthe jugal-gingival groove ( five) and the lips ( five).\nA gynaecological cytobrush was used to perform\nthe examination (Figure 1). To test whether smears\nwere satisfactory or not, a Giemsa quick-staining\nmethod (Hemacolor, Merck, Darmstadt, Germany)\nwas applied, and if necessary the sampling was\nrepeated. Subsequently, smears were stained with\nMay–Gru¨ nwald–Giemsa and Papanicolaou stains.\nResults\nOf the 86 cases undergoing cytological analysis, 63\nwere reported as malignant (60 primary BCCs and\nSCCs (Figures 2 and 3), and three metastatic adeno-\ncarcinomas from the breast, kidney and gastrointesti-\nnal tract) and 21 were reported as benign (Table I).\nCytological analysis resulted in one false negative\nresult, a misdiagnosis of keratoacanthoma. Histologi-\ncal analysis documented a SCC arising on the\njugal-gingival groove. Histological analysis also\nrevealed one false positive result, concerning a case\nof endometriosis occurring in the nose, which was\ncytologically interpreted as a BCC (Figure 4).\nOur cytological method showed a high rate of diag-\nnostic accuracy, with 98.43 per cent sensitivity and\n95.45 per cent specificity (95 per cent confidence\ninterval).\nDiscussion\nDisorders in the head and neck are accessible to\ninspection and palpation. Therefore, biopsy is the\nestablished diagnostic approach, providing the clini-\ncian with accurate histological evaluation. Cytological\ndiagnosis of common primary cutaneous tumours,\nboth benign and malignant, such as SCC and BCC,\nis well documented in the literature.\n7 When faced\nwith the differential diagnosis of cutaneous BCC\nversus cutaneous SCC, a reasonable first approach\nwould be immunostaining for epithelial membrane\nantigen (EMA) and epithelial specific antigen Ab-9\n(clone Ber-Ep4). Negativity for the former and posi-\ntivity for the latter would favour a diagnosis of BCC.\nCytology can almost always detect malignancy, so it\nplays an important role in the pre-operative investi-\ngation of primary skin tumours, as well as in the evalu-\nation of possible metastasis from a previously\ndocumented neoplasm. This has been proven in our\nwork too, with the exception of one case misdiag-\nnosed as keratoacanthoma, and another one misdiag-\nnosed as BCC. In cases of metastatic deposits, it is\nnecessary to detect and manage the primary site.\nIn our study, there were three cases of metastatic\nadenocarcinoma, primarily arising from the breast,\nkidney and gastrointestinal tract.\nDistinguishing keratoacanthoma from squamous\ncell carcinoma is a persistent issue in pathology\npractice. Putti et al.\n8 have reported that analysis of\ntelomerase activity, cyclooxygenase isoenzyme 2\n(COX-2) and p53 expression provides evidence that\nkeratoacanthoma and squamous cell carcinoma are\nindeed distinct lesions and also helps differentiate\nthe two lesions, despite their similarity on convention-\nal morphology. Keratoacanthoma has recently\nbeen reclassified as squamous cell carcinoma-\nkeratoacanthoma type to reflect the difficulty in histo-\nlogical differentiation as well as the uncommon but\npotentially aggressive nature of keratoacanthoma.\nThe term ‘squamous cell carcinoma-keratoacanthoma\ntype’ has been introduced for otherwise classical ker-\natoacanthomas that reveal a peripheral zone formed\nFIG.1\nThe cytobrush used to perform the examination.\nFIG.2\nBasal cell carcinoma arising in the temporal area (May–\nGru¨ nwald–Giemsa; /C2 400).\nBRUSHING CYTOLOGY IN HEAD AND NECK LESIONS 677\nhttps://doi.org/10.1017/S0022215107007104 Published online by Cambridge University Press\n\nby squamous cells with atypical mitotic figures, hyper-\nchromatic nuclei and loss of polarity to some degree.\nThese marginal cells may also penetrate into sur-\nrounding tissue in a more aggressive pattern.\nIn the case of endometriosis misdiagnosed on\ncytological analysis as BCC, the smears contained\nfragments of palisading epithelial cells resembling\nthose of BCC, with uniform nuclei and a bland\nchromatin pattern. No stromal cells were recognised.\n7\nIn theory, cutaneous metastases may result from\nany neoplasm; this is borne out in practice. 9 To\nmake a diagnosis of sweat gland carcinoma, one\nshould first establish that the tumour shows sweat\ngland differentiation, as recognised by identification\nof extracellular ductal or intracytoplasmic lumen\nformations. This can be highlighted by their\ndiastase-resistant periodic acid-Schiff, EMA, and\ncarcinoembryonic antigen positivity. Demonstration\nof S-100 protein may be a useful pointer to sweat\ngland differentiation. Distinction of some types of\nsweat gland carcinoma from metastatic adenocarci-\nnoma is not possible on morphological grounds.\nImmunohistochemical analysis does not allow dis-\ntinction between a primary adnexal tumour and a\nmetastatic tumour, except in a few cases (i.e. prostate\nand thyroid). Malignant sweat gland tumours are\noften positive for oestrogen and progesterone recep-\ntors, and these markers are therefore of limited usage\nin the differential diagnosis. Finally, there are some\nbenign lesions which can be cytologically diag-\nnosed.\n10 – 13 Cytological analysis can rule out metas-\ntasis from a documented neoplasm in followed-up\npatients with newly arisen skin lesions. Cytological\nanalysis can also diagnose uncommon cystic lesions\n(e.g. keratin cysts) and inflammatory processes.\nSignificant indications for the brushing cytology\nmethod are as follows (Table II). Firstly, in cases in\nwhich rapid diagnosis is needed; a skin brushing can\nbe stained and accurately interpreted in a few\nminutes, and this simple method requires no freezing,\nparaffin embedding or microtome. Secondly, in cases\nin which a biopsy is not possible: this may be due to\npatient refusal, lack of tissue-processing facilities,\ninaccessibility of the lesion or the danger of biopsy\ncomplications. Thirdly, in cases in which a biopsy is\nnot needed; the physician need only to confirm a clini-\ncal diagnosis with a minimum of trauma or pain (e.g. a\ncutaneous lesion which is obviously benign and needs\nno biopsy but is of unknown aetiology, or a lesion for\nwhich the possibility of occult malignant change must\nbe ruled out). Fourthly, in cases in which follow up of\ntreated lesions is required, and in which repeated\nbiopsies would be wasteful and /or poorly tolerated\nby the patient; cytology is usually highly sensitive in\nthe diagnosis of recurrence when a good specimen is\nobtained. Fifthly, brushing cytology may be indicated\nas an adjunct to excisional biopsy frozen section, for\nexample, in order to evaluate the persistence of\ntumour cells in the margins of an excision. Sixthly,\nbrushing cytology may be indicated for its safety;\nbiopsy of certain tumours (e.g. malignant melanoma)\nmay release neoplastic cells into lymphatic and blood\nvessels, whereas gentle brushing for cytological analy-\nsis decreases the chances of such an occurrence.\n14\n. This study investigated the use of brushing\ncytology in cutaneous lesions of the head and\nneck\n. Cytology correctly identified 63 of 64\nhistologically documented malignant tumours\nof the skin of the head and neck\n. Brushing cytology was a rapid and reliable\ndiagnostic method which could be performed\nin an out-patient setting\nTABLE II\nINDICATIONS FOR BRUSHING CYTOLOGY\nRapid diagnosis required\nBiopsy not possible\nBiopsy not needed\nFollow up of treated lesions\nAdjunct to biopsy\nSafety\n/C3\n/C3 Avoiding dissemination of disease.\nFIG.3\nSquamous cell carcinoma arising on the upper lip (Papani-\ncolaou; /C2 400).\nTABLE I\nRESULTS\nMethod Total cases ( n) þve (n) 2ve (n)\nCytology 86 63 21\nHistology 86 63 23\nTrue positives ¼ 63; true negatives ¼ 21; false positives ¼ 1;\nfalse negatives ¼ 1. þve ¼ positive; 2ve ¼ negative\nFIG.4\nEndometriosis, misdiagnosed as basal cell carcinoma (Papani-\ncolaou; /C2 400).\nD TAMIOLAKIS, E PROIMOS, G E PEROGAMVRAKIS et al.678\nhttps://doi.org/10.1017/S0022215107007104 Published online by Cambridge University Press\n\nBrushing cytology has some limitations, including:\nthe absence of a cell pool in which cells may accumu-\nlate and remain moist; the difficulty of penetrating\nthe superficial, horny, squamous layers to access\ndiagnostic cells in deeper lesions; the comparative\nease of obtaining punch biopsies; and cytologists’\nunfamiliarity with this type of specimen.\nConclusions\nDespite the exponential interest and growth in\ndermatopathology over the years, and the fact that\nthe skin is the largest desquamating organ in the\nbody, interest in cutaneous cytology has in the past\nbeen limited. Although not a substitute for standard\nhistological analysis, in the hands of an experienced\ncytopathologist, brush smears can aid in establishing\nthe clinical diagnosis with ease and rapidity and can\nserve as an adjunct to routine histological study.\nThe technique is cheap, easy to perform and does\nnot cause any discomfort to the patient. In remote\nareas where facilities for full histopathological\nexamination are unavailable, brushing cytology may\nrepresent a simple and useful diagnostic adjuvant.\nBrushing cytology’s reliability, rapidity and easy\nperformance without anaesthesia warrant serious\nconsideration of its application within the field of\nhead and neck surgery.\nReferences\n1 Orell S, Sterrett G, Walters M, Whitaker D. Supporting\ntissues. In: Orell S, Sterrett G, Walters M, Whitaker D, eds.\nManual and Atlas of Fine Needle Aspiration Cytology ,\n2nd edn. New York: Churchill Livingstone, 1992;300–34\n2 Linsk JA, Franzen S. Melanomas and skin nodules. In:\nLinsk JA, Franzen S, eds. Clinical Aspiration Cytology ,\n2nd edn. Philadelphia: JB Lippincott, 1989;319–36\n3 Reisner K, Haase W. Electron beam therapy of primary\ntumors of skin. Radiol Med 1990;8:114–15\n4 Dogan B, Harmanyeri Y, Balooglu H, Oztek L. Intrale-\nsional Alfa-2a interferon therapy for basal cell carcinoma.\nCancer 1995;91:215–19\n5 Greenway T, Cornell C, Tanner J, Peets E, Bordin M,\nWagi C. Treatment of BCC with intralesional interferon.\nAcad Dermatol 1986;15:437–43\n6 Canti G. Skin cytology and its value for rapid diagnosis.\nActa Cytol 1979;23:516–17\n7 Orell S, Sterrett G, Walters M, Whitaker D. The tech-\nniques of FNAC. In: Orell S, Sterrett G, Walters M,\nWhitaker D, eds. Manual and Atlas of Fine Needle Aspira-\ntion Cytology, 2nd edn. New York: Churchill Livingstone,\n1992;8–23\n8 Putti T, Teh M, Lee YS. Biological behavior of keratoa-\ncanthoma and squamous cell carcinoma: telomerase\nactivity and COX-2 as potential markers. Modern Pathol-\nogy 2004;17:468–75\n9 Reingold IM. Cutaneous metastases from internal carci-\nnoma. Cancer 1966;19:162–9\n10 Duperrat B, Badillet G. Cytological examination of Bullae\nand Vesicles [in French]. Rev Cytol Clin 1971;4:9–16\n11 Dey P, Das A, Radhika S, Nijhawan R. Cytology of\nprimary skin tumors. Acta Cytol 1996;40:708–13\n12 Rege J, Shet T. Aspiration cytology in the diagnosis of\nprimary tumors of skin adnexa. Acta Cytol 2001;45:715–22\n13 Cheng L, Binder SW, Cajjar NA, Hirchowitz SL. Fine\nneedle aspiration as an adjunct to the diagnosis of a rare\nadnexal tumor of hair follicle origin: trichoblastoma.\nDiagn Cytopathol 2003;29:225–8\n14 Naib Z. The vulva and the skin. In: Naib Z, ed. Cytopathol-\nogy, 4th edn. Boston: Little, Brown & Co, 1996;199–217\nAddress for correspondence:\nDr Chariton E Papadakis,\n1 Akrotiriou St,\nChania,\nCrete 73133, Greece.\nFax: þ30 2821055654\nE-mail: papch@otenet.gr\nDr C E Papadakis takes responsibility for the integrity\nof the content of the paper.\nCompeting interests: None declared\nBRUSHING CYTOLOGY IN HEAD AND NECK LESIONS 679\nhttps://doi.org/10.1017/S0022215107007104 Published online by Cambridge University Press","source_license":"public-domain-us","license_restricted":false}