Fine Needle Aspiration Cytology of Eccrine Skin Adnexal Tumors

Material and Methods: This is a retrospective study of fine needle aspiration cytology of subcutaneous swellings over a period of two years from January 2009 to December 2010 in a tertiary care center. A total of 2400 cases of dermal and subcutaneous swellings, for which fine needle aspiration cytology was done with histological follow up, were included in the study. The aspirates were provisionally diagnosed as basaloid neoplasms of skin adnexal origin. The aspirates were further grouped into benign and malignant lesions based on cell morphology and correlation between cytological and histological diagnoses was assessed.


Introduction
Eccrine glands are sweat glands which are appendages of epidermis of skin [1]. They secrete sweat, serve in the regulation of heat and contribute to general cutaneous homeostasis.
Tumors of eccrine glands are proliferations of eccrine ductal or glandular tissue or both in a hyalinized stroma, with lymphocytes as the main inflammatory infiltrate [2].
The present study is undertaken because fine needle aspiration cytology of skin lesions is not widely practiced. Also the literature contains very few reports about cytology of eccrine gland tumors and there is lack of adequate cytological diagnostic criteria of various entities.
Fine needle aspiration cytology (FNAC) is a simple, safe, quick, cost effective and informative procedure. FNAC can be used as complement to histopathology.
The aim of the present study is to utilise fine needle aspiration cytology as a diagnostic investigation for eccrine gland tumors at all possible dermal and subcutaneous sites.

Materials and Methods
The study was conducted in the combined departments of Dermatology and Pathology over a period of two years (2009)(2010). Majority of the aspirations were performed in the department itself by cytopathologists. Prior to aspiration detailed history with physical examination of the lesion were carried out to assess the size, tenderness, plane of the swelling, and clinical evidence of malignancy. Fine needle aspirations were performed with 24 gauge needles and 10ml syringes to obtain scanty and cellular aspirates. Samples were smeared onto glass slides and fixed as necessary. Wet fixed smears were stained with hematoxylin -eosin ( H and E) while air dried smears were stained with May-Grunwald-Giemsa (MGG) stains.
Amongst a total of 2400 cases of subcutaneous swellings aspirated during the study period, twenty cases of skin adnexal lesions with followup excision biopsy formed the crux of the study.
Each slide was reviewed by the cytologist who was blind to the original cytological and histopathological diagnoses.
The cytological smears were studied in the context of the available clinical findings. The aspirates were evaluated for cellular features, associated background and coexisting features as shown in the Table 1.
We also classified all the smears into benign and malignant lesion based on cell morphology. The criteria for benignancy were cohesive clusters, uniform appearing cells with bland nucleus, regular nuclear contour and fine chromatin. The criteria for malignancy were dyscohesive cells, cellular pleomorphism, nuclear enlargement, irregular nuclear shape, contour, chromatin irregularities, atypical mitotic figures and presence of necrosis.
So the final cytodiagnosis of the tumor was benign or malignant basaloid neoplasm of skin adnexal origin. No attempt was made for specific identification of tumors on cytology.
Excision biopsy of the lesion was done and the histological samples were processed and studied using standard procedures.
Light microscopic diagnosis of the slides were performed. Cytohistological correlations were attempted considering histological diagnosis as final.

Results
During the study period, a total of 2,400 cases of subcutaneous swellings were aspirated with adequate aspiration in 2000 cases. Among these cases, 20 cases were cytodiagnosed as basaloid tumors of skin adnexal origin accounting for 0.01% of neoplasms.
Majority of the cases occured in the adult and elderly age groups. 35% of the tumors (7 cases) occured in the 41-60 year age group, 30%(6 cases) in the 21-40 year age group and 25%(5 cases) in the 61-80 year age group. The remaining 10% in the 0-20 year age group.
In our study there was a male predilection accounting for 65% (13 cases). Females constituted 35%(7 cases). The sites, in the descending order of their occurrence were-face, (6 cases), scalp (5 cases), extremities (4 cases), neck (3cases), chest (2 cases). The size of these tumors varied between one centimeter and four centimeters. 95% (19 cases) of the swellings were slowly growing. Recurrance was seen in only one swelling (papillary digital adenocarcinoma). 65% of the cases occured in the subcutaneous plane and 35% (7 cases) in the cutaneous plane. Cystic consistency was observed in 3 cases and tenderness was observed in 2 cases.
The 20 cases were cytodiagnosed as benign and malignant basaloid neoplasms of skin adnexal origin.

Discussion
Eccrine sweat glands, which are appendages of the skin, start developing as early as the fourth gestational month, from the germ cells in the basal layer of the epidermis and are fully developed at the time of birth [1]. Eccrine glands are seen any where in the body but are particularly distributed in the palms and soles [1].
Eccrine glands are composed of three segments -intra epidermal duct or acrosyringium, intra dermal duct, and secretory coil lying in the lower half of dermis or between the dermis and subcutaneous fat [1]. The cytology of the eccrine glands consists of ductal epithelial cells, secretory cells, myoepithelial cells with spindle shaped nucleus, and long contractile fibrils and hyaline basement membrane and collagen fibrils [1][2][3].
Tumors of the eccrine gland can arise from any of the three segments of the eccrine gland mentioned above [2,3] (Table 3). Eccrine tumors of sweat gland can occur anywhere in the human body with a predilection to head and neck region, palms and soles, extremities and ventral surface of body [2][3][4]. Eccrine tumors have a wide range of age distribution starting in childhood and extending into adulthood with no particular sex distribution. They vary in size from few millimeters to several centimeters. They are solitary or multiple. They present as papules, nodules and cystic lesions. They are sessile or pedunculated. They occur in the cutaneous, dermal or in the subcutaneous plane. Spiradenoma present as painful masses. Secondary changes like ulceration, bleeding, pigmentation can occur.

Eccrine spiradenomas
Eccrine Spiradenomas was first described by Kersting and Helwig [4]. The cytology of these tumors has been described by Varsa et al. [5] and Kim [6]. It is similar to the one found in our study. The cytology consists of uniformly sized cuboid cells with scant cytoplasm, round     to oval bland nucleus and inconspicuous nucleoli, arranged as tight multilayered clusters, tubules and rosette formation. The presence of scattered naked nuclei, spindle shaped myoepithelial cells and dense lymphocytic infiltrate distinguish this tumor cytologically from other eccrine tumors [7].

Eccrine acrospiroma
Eccrine Acrospiroma is also called as nodular hidradenoma. The cytology has been described by Punia et al. [8] and Kim et al. [9] .The cytology is similar to the one found in our study. These tumors are composed of tight clusters or sheets of small round cells with a dark nucleus, clear cytoplasm and distinct cell membrane and polygonal cells with a rounded nucleus and slightly basophilic cytoplasm. Transitional cells between these two varieties with eosinophilic cytoplasm, fragments of hyalinized stroma, keratinizing cells are present [2].

Chondroid syringoma
Chondroid Syringoma is described as mixed tumor of skin or pleomorphic sweat gland adenoma [10]. We have reported the cytological features of 2 cases. The cytology is composed of cuboidal epithelial cells, arranged as acini , groups, solitary cells, flattened myoepithelial cells, presence of cells with abundant hyaline cytoplasm [11]. The stroma varies from vaguely eosinophilic to basophilic representing loose reactive fibrous tissue, myxoid. tissue or solid

Papillary eccrine adenoma
Papillary eccrine adenoma is an un common benign sweat gland tumor originally described in 1977 by Rulon and Helwig [14]. Cytologically, it is characterized by basaloid cells with scant cytoplasm and bland nucleus in papillary fragments. Eosinophilic fragments of fibrovascular core are also obsvered.

Eccrine dermal cylindromas
Eccrine dermal Cylindromas are also called turban tumors [3,15]. Cytologically these tumors are composed of islands of epithelial cells arranged in a palisaded manner. The cells are of 2 types -those with dark staining nuclei, and those with light staining nuclei. Thick hyaline bands made up of collagen fibrils which represent subepidermal lamina densa are seen within the cell cluster or separating them.

Eccrine syringomas
Eccrine syringomas consist of cords and groups of ductal epithelial cells with bland nucleus, groups of basaloid cells, vacuolated cells with keratohyaline granules, fragments of stromal tissue [2].

Eccrine poromas
Eccrine poromas are made up of uniform cuboidal or round epithelial cells with deeply basophilic nucleus in sheets, anastomozing bands and cords with intercellular bridges, clear cells and fragments of fibrovascular tissue [2].
Malignancy arising from eccrine glands constitute only a minute fraction of sweat gland neoplasms [3]. The malignant eccrine tumors can occur denovo or certain benign eccrine tumors of long standing duration transform into malignancy. Benign tumors like eccrine spiradenomas, acrospiromas, syringomas cylindromas can undergo malignant transformation [2,3]. Clinically, the transformation is heralded by rapid growth of a long standing cutaneous, nodule and attainment of large sizes. Cytologically, transformation is characterized by loss of nested or trabecular pattern of cell distribution, cellular atypia, nuclear pleomorphism and hyperchromasia, increased mitotic rate, necrosis and absence of dual cell population.
Sweat gland adenocarcinomas: are cytologically characterized by pleomorphic epithelial cells, predominantly dispersed, forming clusters and glandular structures [2]. The cells have moderate to abundant cytoplasm, large irregular nucleus with coarsely granular chromatin, containing visible nucleoli of various sizes. Atypical mitotic figures and necrosis may be seen [16,17].
Mucinous or adenocystic carcinoma: is characterized by clusters of cohesive epithelial cells floating in lakes of mucin. The nuclear abnormalities like nuclear enlargement are slight. They have small nucleoli [2,16,18].
Cutaneous adenoid cystic carcinoma: is characterized by epithelial cells and an acellular basement membrane material [21]. The epithelial cells are arranged in cohesive, often spherical or tridimensional globoid clusters of various sizes. They are relatively small with basaloid appearance, scant cytoplasm, and small but clearly visible nucleoli. The acellular homogeneous basement membrane substance are eosinophilic and transparent [2].
Digital papillary adenocarcinoma: The cytology of digital papillary adenocarcinoma shows tissue fragments consisting of syncytial aggregates and complex folded branching sheets of pleomorphic epithelial cells with a distinct anatomical border. The tissue fragments show nuclear crowding and overlapping. Fibrovascular core traverse or circumscribe the tissue fragments. The cells have enlarged ovoid pale nuclei, finely granular chromatin , distinct nucleoli and dense cytoplasm with distinct cell borders [22,23].
Malignant eccrine tumor the porocarcinomas, aggressive digital papillary adenocarcinomas, malignant hidradenomas metastasize to the regional lymph nodes and distant sites like lungs [2,3].
The eccrine skin adnexal tumors have to be differentiated from other cutaneous and subcutaneous lesions having similar cytology ( Table 4).
The diagnosis of eccrine tumors sometimes cannot be made with certainity on cytology or histology, in which case immunohistochemical differentiation of the eccrine tumors can be made [24]. CK7 ( cytokeratin) and CD34 (cluter differentiation)are markers for secretory coil, CK6 and CK10 are markers for the straight portion of the eccrine duct and SMA (smooth muscle actin) and CD10 are markers for myoepithelial cells. Syringomas show positivity for CK6 and CK10 marker indicating that they arise from eccrine duct. Cylindromas and spiradenomas are positive for CK7 indicating that they arise from secretory coil.

Conclusion
Though there is paucity of case reports describing the cytomorphological features of eccrine tumors, fine needle aspiration can be used successfully as a very simple diagnostic investigation for eccrine skin adnexal tumors. In many cases it can exclude or confirm malignancy and in these instances help to outline surgical management.