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Fine Needle Aspiration Findings Differential Diagnosis Problems. Pitfalls. Uncommon Tumors Immuno cy to chemistry

Dr. Daskalopoulou Dimitra Cytopathology Department Anticancer-Oncologic Hospital of Athens "StSavas"

Athens 2000


Preface -Introduction.................................................................................. 3 Sampling and Staining Methods ................................................................. 6 Cytology of skin tumors and tumor-like conditions.................................... 8 Benign Cystic Tumefactions...................................................................... 11 Benign tumors of the epidermal appendages............................................ 13 Benign tumors and tumor-like conditions of the dermis and subcutaneous fat........................................................... 15 Primary malignant tumors of the skin ...................................................... 20 Primary malignant tumors of the dermis and subcutaneous fat ................................................................................ 25 Malignant cutaneous lymphoproliferative disease ................................... 27 Discussion ................................................................................................. 29 References ................................................................................................. 32


Preface - Introduction

Fine needle aspiration cytology (FNAC) is a well recognized modality of diagnosis of various organ systems! 1). Although text books describe FNAC of skin lesions'2'3', it has not become as yet widely practised, mainly because surgical excision and biopsy are relatively easy procedures. However, there are many cases in which an accurate diagnosis must be established in order to apply either radiotherapy t4"6' or local chemotherapy!7"9!. These non surgical treatment alternatives would be of significant value in selected patients: elderly persons with heart diseases or under systematic therapy, patients with multiple, extensive skin lesions in whom surgical treatment may cause complications, patients in whom more that 2-3 skin lesions occur at a considerable distance from each other on the head and neck, where restoration demands an extensive skin allograft, e.t.c. In the above cases confirmation of malignancy as well as typing of the neoplasm can accurately be accomplished by FNAC. The procedure is non-traumatic, safe, inexpensive and very well tolerated by the patients. The cytological results, when a considerable experience exists, are available within a few minutes. The use of FNAC is justified especially in those cases which have to be investigated for recurrence of a previously treated neoplasm, particularly when multiple lesions are suspected of being recurrences. This is most frequently the case with basal cell carcinoma (BCC), a skin tumour notorious for relapses, since 40%


of the patients with BCC present with a relapse within 10 years! 101. When the surgical biopsy material is obtained from sites in which surgical excision, plastic surgery and even additional radiotherapy has been performed the extremely difficult healing presents a serious problem. The harmful intervention in sensitive tissues can be avoided by using FNAC. The patient is spared unnecessary trouble when his problem is dealt with and solved in a very short time during his follow-up visit to the hospital. Furthermore FNAC can be of value in specialized dermatology centres where a rapid diagnosis must be established in cases where the clinical examination is equivocal, i.e. in differential diagnosis problem between BCC and solar or senile keratosis, sebaceous gland hyperplasia, radiodermatitis consequences, etc. Finally another important application of FNAC is in the follow-up of patients with chronic dermatoses such as "lichen sclerosus et atrophicus of the vulva", balanitis xerotica obliterans, late radiation dermatitis and scars from old thermal burns. In all the above cases, the development of a malignancy is possible. The most common malignant tumors rising from a chronic disease background are squamous cell carcinoma (SSC) and basal cell carcinoma (BCC). Nevertheless the cytopathologist who serves a routinely busy laboratory must be familiar with a far wider spectrum of skin lesions. While the cytological diagnosis of common primary cutaneous malignant tumors such as SCC, BCC and melanoma are well documented in the literature uncommon


skin tumors and tumor-like conditions are seldom described from a cytologic point of view. In this text we report the special cytologic features of common and uncommon cutaneous and subcutaneous tumors and tumor-like conditions.


Sampling and Staining Methods.

In 1979, Cantil11! reported his study based on scraping of 2547 skin lesions. His results were considered very satisfactory. In our experience, the method of scraping a lesion can produce a number of non diagnostic smears and furthermore subcutaneous tumors are not accessible. This technical problems can be solved by using FNAC. Fine needle aspiration of the usual exophytic lesions is performed using a 2127 gauge needle. Insulin needles may be used to aspirate flat lesions and those suspicious of melanoma. When the tumor is well palpable, a simplified cytologic method of fine needle sampling without aspiration may be performed!12]. Withdrawal of the needle alone through the lesion can yield sufficient material for the establishment of the diagnosis. Thus, the production of a bloody material can be avoided. An effort is always made to move the needle gently in the lesion in order to avoid a harmful intervention or hemorrhage in the tissues. The hemorrhage not only produces unsuitable for diagnosis cytologic smears but also may obscure the subsequent histologic study. When the FNA is performed by the cytolpathologist it is necessary to apply the quick Giemsa staining (ex Hemacolor, Merk, Germany) on at least one smear in order to examine immediately the material adequacy. In cases of inadequate material the procedure is repeated, thus cases with diagnostically insufficient material are limited. A number of airdried smears are stained


with May Grunwald-Giemsa and the rest, fixed in alcohol 90°, are stained according to Papanicolaou method. Both staining methods are necessary for an accurate cytologic diagnosis. In cases where the morphologic study is not sufficient for a straightforward diagnosis an additional immunophenotypic study may follow.

Immunocytochemistry is applied, using the appropriate panel on monoclonal antibodies, on freshly dried smears.


Cytology of skin tumors and tumor-like conditions. It is necessary to stress that FNA cytology cannot replace histology in all tumoral skin lesions as there is a considerably large number of tumors and tumor-like conditions in which tissue architecture is of paramount importance for the accurate diagnosis. Under certain circumstances, FNA interpretation cannot be more than a benign/malignant diagnostic consideration. FNA cytology has its place in a well defined clinical protocol taking into account that in the context of benign primary cutaneous neoplasms FNAC has little to offer in terms of taxonomic diagnostic accuracy. Definite cytologic diagnosis can be established in the following tumors: A. Primary benign skin tumors and tumor-like conditions * Cutaneous cysts: bronchogenic, dermoid, epidermoid, digital cutaneous myxoid cyst. * Benign tumors of the epidermal appendages:

pilomatrixoma, chondroid syringoma, cylindroma, eccrine poroma, steatocytoma, trichoepithelioma. * Tumors faciitis, hsitiocytoma, tumor, of the lipoma, dermis and subcutaneous fat: nodular fibrous glomus

cutaneous granular

leiomyoma, cell tumor,

neurolemmoma, heterotopias





B. Primary malignant skin tumors * Basal cell carcinoma (BCC) and variants: pigmented, adenoid, keratotic, metatypical. * Squamous cell carcinoma (SCC) and variants: typical well, moderately, low differentiated SCC, spindle cell, verrucous. * Melanoma and variants: epithelioid, spindle cell, amelanotic, ballon cell, small cell. Only different cell types are recognized cytologically. No growth (radial or superficial) patterns can be recognized. Lentigo maligna cannot be differentiated from infiltrating melanoma. * Tumors of the epidermal appendages: sebaceous carcinoma, malignant eccrine poroma, malignant cylindroma, malignant chondroid syringoma, primary cutaneous adenoid cystic carcinoma, apocrine carcinoma. * Neuroendocrine carcinoma of the skin (Merkel cell carcinoma). C. Primary malignant tumors subcutaneous fat * * * * * * Liposarcoma Maligmant fibrous histiocytoma Kaposi's sarcoma Angiosarcoma Fibrosarcoma Neuroectodermal tumors


of the dermis and

* * * *

Rhabdomyosarcoma Alveolar soft part sarcoma Synovial sarcoma Malignant cutaneous lymphoproliferative diseases: B and T-cell non Hodgkin's lymphomas.


Benign Cystic Tumefactions

* Cutaneous bronchogenic cyst:

Fine needle aspiration drains a mucinous material. Microscopic examination shows numerous groups of benign, columnar, ciliated cells, some with eccentric nucleus and abundant cytoplasm. The latter is PAS positive, diastase resistant. Many histiocytes and lymphocytes, along with cell debris and some squamous cells are scattered in a mucinous background. The overall cytologic appearance is that of a bronchial brushing. Cutaneous cystic lesions with columnar, ciliated epithelium maybe also of Mullerian derivation!


1, but they affect always females and are almost

exclusively located at the buttocs and the lower limbs. Microscopically they lack goblet cells, in contrast to bronchogenic cystst14!. * Dermoid cyst:

The aspirated material is thick and tan. Microscopically many aggregates of mature and anucleated squamous cells are observed and also many cohesive acinar cells in typical arrangements of sebaceous glands. The background is dirty, full of cell derbris and histiocytes. The cytological findings are not specific of the lesion. Steatocytomal15! may produce exactly the same cytologic material but it mainly affects adults and almost always presents as multiple lesions spread over the face, neck and the upper trunk.



Epidermoid cyst:

The lesions present as sohtary, almost spherical, suberpidermal nodules, skin colored or dark yellow, sometimes with central punctum. Aspiration yields a thick material composed almost exclusively of anucleated squamous cells. Fine needle aspiration of mature pilomatrixoma may produce a similar material but in this case even if basaloid cells are absent and only ghost cells remain, prominent calcification and multinucleated giant cells are almost always present. * Digital myxoid cyst:

The clinical futures of the cyst are characteristic: spherical, translucent, tender nodule on the dorsal aspect of the distal interphalangeal joint of the medius finger. Longitudinal grooving of the nail is evident. A mucinous material is drained. Microscopically some benign

spindle cells -probably fibroblasts- are found embedded in a thick mucinous background. .


Benign tumors of the epidermal appendages

* Pilomatrixoma: (calcifying epithelioma of Malherbe): In the aspirated material we observe many small, basaloid cells in loosely arranged sheets, tight clusters or dispersed. Their nuclei are round, uniform, fairly regular, with finely granular, evenly distributed chromatin and small distinct nucleoli. Their cytoplasm -when evident- is scanty, light grey with MGG. In some cases cells appeare in a syncytial arrangement. The dispersed cells have either a narrow rim of cytoplasm or, most commonly, they present as stripped nuclei. A significant amount of mature squamous cells with picnotic nuclei and ghost cells in the form of pale, anucleated squames are also found. Many flecks of calcium are noted either dispersed or in the basaloid cell clusters. The background is dirty with sheets of amorphous material, cell debris, inflammatory cells and some to numerous multinucleated giant cells!16,17!. * Chondroid syringoma: (mixed tumor of the skin):

In aspirated material the striking feature is a fibrillary chondromyxoid substance in the background, stained purple with MGG and orange with Pap stain. The aspirates are cellular consisted of benign epithelial cells arranged in flat sheets or dispersed. The cells are relatively small with round or oval eccentric nuclei, evenly distributed fine chromatin and single, tiny nucleoli. The cytoplasm is dense, moderate in amount with well defined cell borders. Some clusters of epithelial cells show a gradual transition to the myxoid stromal tissue. The cells


embedded in the ground substance are similar to those seen in clusters but some of them are elongated arranged individually or in a fusiform pattern. The differential diagnosis of chondroid syringoma includes metatypical BCC with stromal hyaHnization and malignant mixed tumor of the skin. * Dermal cylindroma: The tumor presents as well circumscribed firm or fluctuant nodule most frequently on the scalp. The most distinctinctive feature in the aspirated material is the homogenous hyahne globules stained purple with MGG and translucent with Pap stain. These globules are surrounded by cohesive benign epitheUal cells with dark uniform nuclei. The background is clean and no mitoses are noticed.


Benign tumors and tumor-like conditions of the dermis and subcutaneous fat

* Nodular faciitis: (pseudosarcomatous faciitis, proliferative faciitis): The lesion presents as solitary, firm, non-tender subcutaneous nodule with a growing course of a few days or weeks. The aspirated material is always cellular, dominated by spindle-shaped fibroblasts with long cytoplasmic processes, large round or ovoid, pale nucleous and prominent nucloelous. The fibroblast are either individual of arranged in cohesive sheets in a streaming pattern. Anisonucleosis is prominent. Many normal mitoses are observed in most cases. The background is invariably myxomatous, never bloody. Some lymphocytes and plasmacells are noticed. These cytologic findings have to be associated with chnical history, features and course in order to make a correct diagnosis, since nodular faciitis' cytologic features overlap with those of fibromatosis, mesenchymal repair, granulation tissue or even fibrosarcoma and malignant fibrous histiocyte ma f1^. * Cutaneous leiomyoma:

The aspirated material is cellular composed of numerous bandies of spindle cells with pale, elongated nuclei, some with the characteristic cigar-shape. The background is metachromatic and clean.


In order to support the diagnosis of a leiomyoma a positive immunocytochemical staining for desmin is necessary. The differential diagnosis based on cytomorphologic criteria alone includes dermatofibroma, benign fibrous, histiocytoma and nodular faciitis. * Benign fibrous histiocytoma:

Benign spindle cells, foamy histiocytes and multinucleated giant cells of foreign body kind are the salient cytologic findings. Macrophages with heamosiderine deposition are often seen. Considered in the differential diagnosis are nodular fasciitis (NF) and malignant fibrous histiocytoma (MFH)[19L * Neurilemmoma (schwannoma):

The aspirated material is consisted of small, irregularly shaped cell clusters and interlacing swirling fascicles of spindle cells with oval, slender nuclei. In some clusters a characteristic palisading may be noticed. Typical "verocay bodies" are found only in few cases. Immunocytochemically all cases are S-100 positive, desmin negativel16J. * Granular cell tumor (cutaneous myoblastoma):

The smears are usually markedly cellular. The tumor cells are either scattered or in loosely cohesive syncytial fragments. They have moderate to abudant finely granular cytoplasm and ill defined cell borders. The nucleous is round with fairly normal chromatin pattern and multiple chromocenters. Some nuclei have prominent central nucleolous. The background has a dirty


appearance. Numerous stripped nuclei are found along with lymphocytes and eosinophils. Immunocytochemistry stains must be performed in order to confirm the morphologic diagnosis. The tumor cells are positive for NSE, S100 and Vimentinf16!. * Glomus tumor:

The FNA of this tumor usually causes severe pain. The smears are very cellular consisted of small rather uniform round cells with central nucleous and small central nucleolus. The cytoplasm is moderate and pale. The cells are arranged individually close to each other, without molding. No epithelial groups are found but in some areas cells tend to form small nests. The differential diagnosis includes melanoma (small round cell amelanotic variant) metastatic carcinoma and paraganglioma. * Cutaneous meningioma:

Meningiomas are the commonest extracerebral intracranial tumours arising from arachnoidal lining (meningothelial) cells. They may also occur in a variety of ectopic sites, including skull bones, glabellar area, orbit, middle ear, nasal cavity, parotid gland, mediastinum, pleura, lung, branchial plexus and skin (scalp, face, neck, paravertebral region)!20211. Meningeal lesions presenting in the skin are usually known as "cutaneous meningiomas" and are extremely unusual. Most lesions in this group are probably hamartomatous or the result of developmental defects; therefore the designation of "meningeal heterotopias" is used. Cutaneous meningiomas are classified into


three types although there is a great degree of overlap, especially histologically, between type I and type III22'. Type I lesions (meningeal dysraphias, or sequestrated meningoceles) are congenital presenting as skin nodules often noted at birth but which may not come to surgical attention until adulthood. Type II lesions present mainly in adulthood on the head and neckl23!. The histologic examination of both type I and type II lesions usually shows a dermal and subcutaneous proliferation of polygonal to spindle meningothelial cells with no atypia, arranged in whorls, dissecting collagen fibers or arranged in solid nests^22'. They are immunoreactive for epithelial membrane antigen (EMA) and vimentin. Type III lesions represent local invasion or true metastasis from a primary intracranial meningioma with similar histological features. A short history from the patient, especially if associated with the presence of cell atypia and mitoses in the histologic material, will make the distinction between type III and type I or type II lesionst22!. The initial diagnosis as well as the distinction between, benign and malignant meningioma can also be accomplished by the use of FNA cytology!24'25,26!. Among the diverse primary Central Nervous System (CNS) tumors, meningiomas present the most constant, accurate and reproducible cytologic diagnostic criteria I25,261, in spite of their histologic heterogeneity.


Cytologic smears show many small collections of whorled spindle cells with bland oval nuclei and incospicuous nucleoli. Occasionally small nuclear inclusions are seen. The cells have pale staining cytoplasm with ill-defined cell boundaries. Some psammoma bodies may be found. The cytologic findings are typical so no differential diagnosis problem is raised. * Pseudolymphoma: The cytologic diagnosis of pseudolymphoma is based initially on the reactive appearence of the lymphoid population that is drained from the lesions. There are many tingible body macrophages and the full range of small and transformed lymphocytes including several dendritic and monocytoid cells. However, some low grade B-cell cutaneous lymphomas present many benign lymphoid follicles with typical germinal center I20'. Thus a cytologic diagnosis based only on the polymorphism of the lymphoid population cannot be accurate. Immunocytochemical stains with a panel of antibodies including kappa, lambda lights chains. CD3, CD 19 and CD22 must be applied in order to confirm the diagnosis 116l


Primary malignant tumors of the skin * Basal cell carcinoma (BCC):

Aspirates from BCC are usually cellular small cuboidal cells are observed in cohesive clumps, some of which demonstrate characteristic palisading at the periphery producing a smooth, scalloped perimeter. A few stripped nuclei may be seen against a clean background. In the majority of cases a pink amorphous substance is noticed surrounding the periphery of the cell clusters. In some cases mitoses are noted. Nucleolus are almost absent in cytologic smears. When melanin granules are found in the cytoplasm of the neoplastic cells and in scattered histiocytes it is the case of pigmented BCC which some times has to be differentiated from melanoma. In some other cases small basaloid cells in a reticulate arrangement may be noticed. Spaces between cells are full of clean myxoid substance. One to three layers of cells surround some narrow myxoid areas. The cell characteristics are that of a BCC but typical cell groups with the peripheral palisading may be rare. This is the case of a BCC adenoid variant. This variant may be a pitfall in cytologic smears. The tumor may be diagnosed as an adenoid cystic carcinoma. * Squamous cell carcinoma:

Squamous cell carcinoma (SCC) is one of the most aggressive skin tumors with high tendency to metastasise. The cytologic appearance of the tumor depends on the degree of differentiation. In the well differentiated SCC smears are consisted mostly of


mature squamous cells with keratinized cytoplasm and large dark-stained nuclei. Tumor cells appear as solitary or in small groups, most of the times with prominent variation in size and shape. The cytoplasm is abundant and deeply eosinophilic. Some nonkeratinized cells may be found. Mitoses are rare. Moderate and low differentiated tumors are consisted of malignant cells with moderate cytoplasm, central or eccentric nuclei, coarse chromatin pattern and prominent nucleoli. There are mononucleate, binucleate, even multinucleate cells. Mitoses are frequent. Squamous cell carcinoma often exhibits cystic degeneration. A dirty fluid material is aspirated. The background is necrotic with variant degree of inflammation and giant cell reaction ("foreign body" multinucleate cells are numerous). * carcinoma: The smears are consisted of large groups of malignant cells with hyperchromatic, mostly central, nucleous and conspicuous nucleolous. The cytoplasm is moderate to abundant and have a characteristic bubly appearance. Cell borders are irregular, some times indistinct. Few mitotic figures may be found and also some foreign body multinucleated giant cells. The background is usually dirty. The differential diagnosis includes sebaceous adenoma, and sebaceous epithelioma. The prominent Sebaceous

pleomorphism and irregularity of the nucleus dismiss a benign tumor. Lipid staining is positive in almost all tumor cells.



Primary adenoid cystic carcinoma of the skin:

The cytologic findings are identical to those described in the litterature concerning the adenoid cystic carcinoma of the salivary glalndsl28! Considered in the differential diagnosis is the benign dermal cylindroma I29' ut the cell charachteristics of adenoid cystic carcinoma are in favor of a malignant tumor: there is prominent nuclear hyperchromatism and crowding. Many abnormal stripped nuclei are found among cell clusters. Rare mitoses may be noticed. Basal cell carcinoma adenoid variant is also considered in the differential diagnosis but the clinical characteristics of the tumor, which is always subepidermal, are inconsistent with a BCC. * Merkel cell tumor (neuroendocrine carcinoma of the skin): The tumor yields a cellular material consisted of small, uniform malignant cells with hyperchromatic nuclei and scanty cytoplasm, resembling to transformed big lymphocytes such as immunoblasts. The cells are arranged mostly individually and rarely in small groups with conspicious molding. Many mitoses may be found. Immunocytochemically the tumor cells express neuron specific enolase (NSE) and are negative in LCA and HMB45 antigen. The latter must be performed in order to exlude a NHL and a melanoma respectivelyI30-311.


* Melanoma: The smears are cellular consisting mostly of solitary melanoma cells. Four different cell types can be recognized cytologically. The most common type is the epithelioid with melanin pigmentation. In this variant the cells are round or oval with eccentric nuclei and distinct nucleoli. Binucleated cells are numerous The cells can be found in loose groupings or even in cohesive clusters mimicing an epithelial tumor. The presence of melanin in the malignant cells and in scuttered histiocytes supports the correct diagnosis. Another cytologic variant is the spindle cell melanoma consisting almost entirely of spindle cells with elongated nuclei. These cells are presented as solitary forms or in groups of intermigled cells mimicing a spindle cell sarcoma. The undifferentiated type of melanoma is composed of small, round cells similar to big lyphocytes. This type of tumor has to be differentiated from a high grade non-Hodgkin's lymphoma and Merkel cell tumor. The anaplastic type of melanoma is composed of polymorphic giant cells with one, two or multiple nuclei. Amelanotic forms are more common. The cells are round, balloon-like or elongated with long cytoplasmic processes. All cell types of melanoma tumors share some common cytologic characteristics: Single cells predominate, polymorphism is common, nucleoli are prominent often multiple, "bird's eye" or "cell in cell" forms are common. Furthermore intranuclear inclusion is


a common finding in all types, except in the undifferentiated small cell variant where is exetremely rare, mitoses are numerous and histiocytes are always present among the tumor cells. Some other malignant skin tumors such as the malignant hydradenoma, and malignant eccrine poroma may present similar cytologic characteristics with the amelanotic epithehoid type of melanoma. In these cases the differential diagnosis is based on immunophenotyping. It has to be stressed that, according to the literature, melanotic skin lesions must not undergone fine needle aspiration not because of a possible spreading of tumor cells but because there is a possibility of serious disturbance of the histologic architecture. Fine needle aspiration may obscure the histologic study because of bleeding or secondary lymphocytic infiltration. In melanome the lymphocytic reaction is considered as a secondary diagnostic and prognostic factor which has to be taken in to considereation along with other histologic parameters. For example host inflammaroty response is more often seen in agressive lesions or in desmoplastic melanoma.


Primary malignant tumors of the dermis and subcutaneous fat.

* Mixoid liposarcoma: The smears are consisted of uniform spindle or oval cells, some with intracytoplasmic vacuoles, arranged in sheets, embedded in a myxoid background. Lipoblast of signet-ring type may be found. Nuclei are pleomorphic, some with conspicuous nucleoli. Malignant fibrous

histiocytoma is considered in the differential diagnosis. * Malignant fibrous histiocytoma:

The tumor yields rich cell samples. Elongated, stellate and fusiform cells predominate. Histiocyte-like giant cells are also found. In some cases the predominant cell type is the polygonal mononucleate of multinucleate giant cell and only few spindle cells are found. In all cases the nuclei vary in size and shape. They are either ovoid, kidney shaped or bizarre with markedly hyperchromatic nuclear membrane and conspicious nucleoli. The cytoplasm is fragile, some times with small vacuoles. In some cases a fibrillar, myxoid substance is visible in the background. Immunocytochemical stains for alpha-1-antihymothrypsin and alpha-1-antithrypsin are positive. * Cutaneous leiomyosarcoma:

The cytologic smears are cellular consisting of cohesive cell clusters. The cells have oval or elongated, cigar-shaped nuclei, and a delicate cytoplasm. Anisokaryosis and an irregular chromatin


pattern is evident in most cases. The background is clean and partially myxoid. * Kaposi's sarcoma: There is scanty to moderate cellularity in smears which are composed of single and cohesive bundles of spindle cells in a bloody background. The cytoplasm of the tumor cells is usually abundant and basophilic and the nuclei are either oval or fusiform with occasional single prominent nucleoli. There is a marked irregularity in nuclear membrane with uneven hyperchromasia and conspicuous grooving. Immunocytochemically the tumor cells are postive for CD31 and CD34 endothelial markers.


Malignant cutaneous lymphoproliferative disease.

The cutaneous lymphomas involve primarily the skin and may affect other sites only secondarily. They include T-cell and B-cell Non-Hodgkin's Lymphomas (NHL). Primary cutaneous manifestation of Hodgkin's Disease (HD) is very rare. Primary cutaneous T-cell lymphoma is largely consisted of Mycosis Fungoides but in the recent years the definition is expanded to include other T-cell malignant proliferative conditions. In fact, cutaneous Tcell lymphoma is a group of NHL with significant heterogeneity. The clinical presentation of such tumors varies greatly. Poikilodermatous dermatosis, erythroderma, hyperke-ratotic plaques, hypopigmented pathces and solitary of multiple tumor nodules are some of the commonest clinical pictures, which have to be differentiated from other benign or malignant conditions. As a first diagnostic approach fine needle aspiration cytology can contribute greatly in the early and correct therapeutic management. Immunophenotyping is of paramount importance for a correct diagnosis. Anti-kappa anti-lamba monoclonal light chains are applied for the detection of monoclonality of the lymphoid population. A light chain restriction is defined as the presence of a K:X or X:K ratio >6:1 after a count of at least 250 cells!32'. T-cell markers such as CD43 and CD45 Ro are applied after both kappa and lambda negative chains results.


Specificities of Antibodies used for cytologic immunophenotyping in lymphoid tumors of the skin

Antigen CD3 CD4 CD5 CDs

CD19 CD22


Exression Pan-T cell Helper/inducer T-cells T-lymphocytes B-subpropulation Cytotoxic-suppressor T-cells Pan-B cell Pan-B cell B cells B cells Common leucocyte (Panhematopoietic) Reed-Sterberg cells, activated cells Proliferating cells


CD45 CD30




Experience has shown that in FNAC, an accurate diagnosis of benign and malignant skin lesions can be not only challenging but also sometimes difficult. The difficulty is due to many factors, the most important being the great variety of morphologic patterns seen in both neoplastic and nonneoplastic skin lesions and the overlapping cytologic features of certain tumors and tumor-like conditions, coupled with the fact that for the bulk of benign skin lesions, tissue architecture is of paramount importance for an accurate diagnosis. Because cytology lacks architectural features, it must be admitted that in the context of benign primary cutaneous neoplasms, FNAC has little to offer in terms of taxonomic diagnostic accuracy. On the other hand, it can almost always detect malignancy. FNAC, therefore, plays an important role in the preoperative investigation of skin tumors as well as in the evaluation of a possible recurrence of a previously treated neoplasm. Numerous studies of FNAC of primary skin tumors as well as a considerable number of case reports have been described in the literature. Among the benign primary skin tumors, mostly chondroid syringoma and pilomatrixoma have been documented. In both of these tumors, the authors have confirmed that the cytologic features of FNAC are distinctive and suggestive of the lesions, mainly because these features include the epithelial and the contrasting stromal components. Masood and Hardy however,


have stated that an accurate differential diagnosis between benign and malignant chondroid syringoma cannot be made on the basis of FNAC, and that the sex of the patient must be taken into consideration as well as secondary clinical features of the lesion (site, volume of the tumor), which may suggest malignancy. Hidradenoma congenital cystic lesions (such as dermoid cyst), and other cystic lesions (such as epidermoid cyst) are seldom described from a cytologic point of view. To our knowledge, no cytologic description of cutaneous bronchogenic cyst and digital cutaneous myxoid cyst has been reported in the literature to date; on the contrary, FNAC of benign subcutaneous tumors (granular cell tumor, myxoma, lipoma, histiocytoma, neurilemmoma, and neurofibroma) is well documented. There have also been some very satisfactory cytologic descriptions of tumefacient, pseudoneoplastic prohferation of fibroblasts and myofibroblasts such as nodular fasciitis and mesenchymal tissue repair. Among the malignant skin tumors other than BCC, SCC, and melanoma, apocrine carcinoma, Merkelcell carcinoma, sebaceous carcinoma as well as tumors of the dermis and subcutaneous fat have been the most commonly described in FNA cytology. With regard to the latter, we agreed that appropriate cytochemical and/or immunocytochemical stains are extremely important for the differential diagnosis. Although controversy still exists with regard to the cytologic diagnosis of malignant lymphoproliferative disease, a significant


number of relevant pubHcations have shown that, not only is cytologic. assessment of these lesions possible, it is also highly accurate. In conclusion, FNAC of primary skin tumors is a safe diagnostic procedure. In the hands of adequately experienced cytologists, reliable results are accessible on technically satisfactory smears.



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