Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases

BACKGROUND: Epithelioid sarcoma is a rare tumor with characteristic morphologic and immunohistochemical features. It can be confused histologically and cytologically with a variety of benign and malignant lesions, including a granulomatous process, synovial sarcoma, melanoma, squamous cell carcinoma, and adenocarcinoma. The objective of this study was to define the cytologic features of this rare tumor. METHODS: The cytologic features of nine histologically confirmed epithelioid sarcomas were analyzed. The criteria evaluated included cell size and shape, cell borders, cluster organization, cytoplasmic characteristics, nuclear and nucleolar features, and background characteristics. RESULTS: In most cases, single, dispersed cells represented the predominant pattern, with only a few small clusters present. The cells were mostly round with interspersed spindle cells and mild to moderate pleomorphism. The nuclei were large and eccentrically located, with a plasmacytoid appearance. A pale zone in the perinuclear area was evident in three of nine cases. Well-defined cell borders with intercellular spaces between malignant cells were observed in eight cases. In three cases, a granuloma-like structure was identified. In two cases, the cells were mostly spindle and showed greater cellular pleomorphism. CONCLUSION: Epithelioid sarcoma is an uncommon tumor with a wide range of differential diagnoses, especially in cytology specimens. Awareness of its existence and knowledge of its cytologic features are important for a correct diagnosis.     

The utility of GLUT-1 immunolocalization in cell blocks: An adjunct to the fine needle aspiration diagnosis of cystic squamous lesions of the head and neck

BACKGROUND: Cytologic distinction of metastatic cystic squamous cell carcinoma (SCC) from benign squamous cell lesions, especially the ones with superimposed inflammatory atypia, can be very challenging. The authors evaluated the usefulness of glucose transporter-1 (GLUT-1) immunostaining as an adjunct to fine-needle aspirations of squamous lesions of the head and neck. METHODS: Immunohistochemical staining for GLUT-1 was performed on paraffin-embedded cell blocks of 28 cases with the following cytologic diagnoses: 1) metastatic SCC (11 cases); 2) atypical squamous cells, SCC [corrected] cannot be excluded (6 cases); and 3) cytologic findings consistent with branchial cleft cyst (BCC) (11 cases). RESULTS: All 11 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for GLUT-1. Tissue follow-up confirmed metastatic SCC in all 11 cases. The squamous cells in all 11 cases with cytologic findings consistent with BCC were negative for GLUT-1; tissue follow-up confirmed diagnoses of BCC in 8 cases. In the remaining 3 cases, excision was not performed, and, clinically, no recurrences were identified at 28, 20, and 16 months of follow-up. Of the 6 cases with cytologic diagnosis of atypical squamous cells, 3 were negative and 3 were positive for GLUT-1. Subsequent excisional biopsies in these cases revealed 4 cases of metastatic SCC (3 positive and 1 negative for GLUT-1), 1 case of BCC (negative for GLUT-1), and 1 case of thyroglossal duct cyst (negative for GLUT-1). CONCLUSION: GLUT-1 immunostaining is a useful adjunct in differentiating benign and malignant squamous lesions in cell-block material. Although negative staining for GLUT-1 does not exclude malignancy, positive immunoreactivity for GLUT-1 may aid in accurate diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the head and neck.     

Nucleolar organizer region count and subjective AgNOR pattern assessment (SAPA) score in skin tumors.

OBJECTIVE: To study the argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytologic and histologic specimens of various skin tumors. STUDY DESIGN: The study group consisted of 37 patients (14 benign and 23 malignant) of various skin tumors. In all cases, cytology by fine needle aspiration cytology (FNAC), and histological specimens were studied by conventional staining and silver staining for AgNOR. RESULTS: The mean count in benign tumors in cytologic specimens was 2.08 +/- 0.01, compared with 5.50 +/- 1.12 in malignant tumors (P<0.001). In histologic specimens, mean count was 2.13 +/- 0.51 in benign, compared with 5.38 +/- 1.10 in malignant tumors (P<0.001). The SAPA score in benign tumors (P<0.001) in cytologic specimens, was 6.07 +/- 0.83, compared with 10.65 +/- 1.27 in malignant tumors, and in histology, it was 6.07 +/- 0.87 in benign, compared with 10.83 +/- 1.15 in malignant tumors (P < 0.001). Melanoma showed the higher AgNOR count compared with squamous cell carcinoma and basal cell carcinoma. The parameters were statistically significant between the grade of tumor in squamous cell carcinoma and the positivity of lymph nodes as demonstrated by SAPA score. No correlation was found between the clinical stage and Clark level of melanoma. Although, AgNOR count and SAPA score showed similar results, the indicators of validity were higher in SAPA than AgNOR count. CONCLUSION: Although, AgNOR count and SAPA score gave similar results, but the indicators of validity were higher in SAPA score than AgNOR count.     

Diagnostic challenges of metastatic spindle cell melanoma on fine-needle aspiration specimens

BACKGROUND: Spindle cell melanoma is a morphologic variant of melanoma that can be difficult to diagnose on specimens obtained via fine-needle aspiration (FNA). Published cytology studies concerning this entity were based for the most part on small series. In the current study, a large series of metastatic spindle cell melanoma is described and the diagnostic pitfalls present in FNA samples addressed. METHODS: The authors retrospectively reviewed the cytologic features of 81 metastatic spindle cell melanoma specimens obtained from 67 patients. Corresponding primary tumors or metastatic tumors taken elsewhere from the same patient were also evaluated. RESULTS: The cytologic smears were mostly cellular and comprised of predominantly spindle tumor cells that frequently formed cohesive fascicles or whorls intermingled with scattered epithelioid tumor cells. The classic cytologic characteristics of conventional melanoma (predominantly dyshesive cellular distribution, cytoplasmic melanin pigments, intranuclear pseudoinclusions, macronucleoli, and binucleation or multinucleation) were noted infrequently or, if present, were more readily found in coexisting epithelioid cells. Remarkably, 9% of the cases failed to demonstrate any of the above classic characteristics. In addition, spindle cells demonstrated a wide range of cytologic atypia, from deceptively bland cells resembling reactive fibroblasts to those indistinguishable from pleomorphic high-grade sarcomatous neoplasms. When the morphologic features were compared with those of the primary tumor or metastatic melanoma taken elsewhere from the same patient, cell type discrepancy was found in 20% of the cases in that the previous counterparts demonstrated the epithelioid cell type. Spindle cells also tended to lose immunoexpression of melanoma markers. CONCLUSIONS: Spindle cell melanoma infrequently demonstrates the diagnostic cytologic features and immunoreactivity of conventional melanoma. Varying degrees of cytologic atypia and possible cell type differences from the primary counterpart or metastatic melanoma occurring elsewhere are additional sources of diagnostic challenges, especially in the metastatic setting. Familiarity with cytologic features, combined with clinical and immunoperoxidase findings, is required to avoid misinterpretation.     

Diagnostic challenges of metastatic spindle cell melanoma on fine‐needle aspiration specimens

BACKGROUND

Spindle cell melanoma is a morphologic variant of melanoma that can be difficult to diagnose on specimens obtained via fine‐needle aspiration (FNA). Published cytology studies concerning this entity were based for the most part on small series. In the current study, a large series of metastatic spindle cell melanoma is described and the diagnostic pitfalls present in FNA samples addressed.

METHODS

The authors retrospectively reviewed the cytologic features of 81 metastatic spindle cell melanoma specimens obtained from 67 patients. Corresponding primary tumors or metastatic tumors taken elsewhere from the same patient were also evaluated.

RESULTS

The cytologic smears were mostly cellular and comprised of predominantly spindle tumor cells that frequently formed cohesive fascicles or whorls intermingled with scattered epithelioid tumor cells. The classic cytologic characteristics of conventional melanoma (predominantly dyshesive cellular distribution, cytoplasmic melanin pigments, intranuclear pseudoinclusions, macronucleoli, and binucleation or multinucleation) were noted infrequently or, if present, were more readily found in coexisting epithelioid cells. Remarkably, 9% of the cases failed to demonstrate any of the above classic characteristics. In addition, spindle cells demonstrated a wide range of cytologic atypia, from deceptively bland cells resembling reactive fibroblasts to those indistinguishable from pleomorphic high‐grade sarcomatous neoplasms. When the morphologic features were compared with those of the primary tumor or metastatic melanoma taken elsewhere from the same patient, cell type discrepancy was found in 20% of the cases in that the previous counterparts demonstrated the epithelioid cell type. Spindle cells also tended to lose immunoexpression of melanoma markers.

CONCLUSIONS

Spindle cell melanoma infrequently demonstrates the diagnostic cytologic features and immunoreactivity of conventional melanoma. Varying degrees of cytologic atypia and possible cell type differences from the primary counterpart or metastatic melanoma occurring elsewhere are additional sources of diagnostic challenges, especially in the metastatic setting. Familiarity with cytologic features, combined with clinical and immunoperoxidase findings, is required to avoid misinterpretation. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Immunohistochemical reactivity of the antimelanoma monoclonal antibody MEL-1

The immunohistochemical reactivity of the monoclonal antimelanoma antibody MEL-1 was evaluated on frozen sections of 9 malignant melanomas, 5 nevi, 1 squamous cell carcinoma, 1 basal cell carcinoma, 2 benign dermal fibrous histiocytomas, 1 infiltrating ductal and 2 infiltrating lobular carcinomas of the breast, 1 primary squamous cell carcinoma and 1 adenocarcinoma of the lung, 1 lung metastasis of gastric adenocarcinoma, 1 adenocarcinoma of the large bowel, 1 lymph node, 1 case of malignant histiocytosis and one of lymph nodal immunoblastic lymphoma, and 1 biopsy of oral cavity mucosa. In primary and metastatic malignant melanoma, junctional nevi, and the upper half of compound and dermal nevi, the staining was intense. Also, benign dermal fibrous histiocytoma and the case of lymph nodal malignant histiocytosis showed an intense reactivity, whereas the immunostaining positivity of the squamous cell carcinoma of the skin, the lung adenocarcinoma, the squamous cutaneous and mucosal epithelium, and the sweat and sebaceous glands was slight. In ductal and lobular infiltrating carcinoma of the breast only focal areas or isolated tumor cells were positive. The lack of reactivity of deep dermal melanocytes of compound and dermal nevi may be correlated with a different antigenic phenotype of the melanocytes. After discussion of the technical problems, the application of MEL-1 was suggested, for diagnostic purpose, to identify lymph nodal metastases in cases of primary self regressed malignant melanoma and to detect lymph nodal metastatic microfoci of malignant melanoma.     

Cytological and cytogenetical analysis of thoracic duct lymph in patients with pulmonary carcinomas

Seven patients with squamous cell carcinomas of the lung and nodular metastases underwent Daniels' biopsy and cannulation of the thoracic duct. Lymph specimens obtained by aspiration the day after catheter insertion were examined by cytologic and cytogenetical techniques, including chromosome banding methods. In five of the seven cases malignant cells could be detected by karyotype analysis, whereas standard cytologic examinations yielded no positive diagnoses. This indicates that chromosome analysis is applicable as a diagnostic tool in lymph fluid.     

Trends in skin cancer incidence in Neuchatel, 1976-98.

AIMS AND BACKGROUND: Limited data are available on trends in skin cancer incidence. This paper examines trends of the three major histotypes of skin cancer in an environment favorable for skin cancer registration. METHODS: Trends of skin cancer incidence by histotype in the Swiss Canton of Neuchatel (165,000 inhabitants) were analyzed on the basis of 4,455 incident cases of basal cell, squamous cell carcinoma, and malignant melanoma registered over the period 1976-1998. RESULTS: Trends over the last decade considered tended to be downwards for squamous cell carcinoma in both sexes, were still on the rise for basal cell carcinoma, and leveled off for malignant melanoma in both sexes. CONCLUSIONS: Different trends were confirmed in this population between skin cancer histotypes related to cumulative intense sun exposure (squamous cell carcinoma) and those mainly related to more complex patterns of exposure to sunlight (basal cell carcinoma and malignant melanoma).     

Cutaneous malignant melanoma in association with other skin cancers

A case-control study of 232 cases of cutaneous malignant melanoma and 232 matched controls was performed to assess the association of the disease with nonmelanotic skin tumors--basal cell carcinomas, squamous cell carcinomas, and solar keratoses. There was a fourfold increase in risk of melanoma of all types when actinic tumors were present on the face. The risk was not restricted to the lentigo malignant melanoma class as might be expected but was significantly raised for superficial spreading melanoma and nodular melanoma as well (relative risk, 2.8; 95% confidence interval, 1.1-7.2). This relationship with lesions known to be associated with high-dose solar UV irradiation was supported by quantitative evidence that heavy sun exposure was associated with an increased risk of malignant melanoma.     

Immunocytochemical characterization of lung tumors in fine-needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma

In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine-needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma.     

Desmoplastic malignant melanoma: A light and electron microscopic study of two cases.

This light and electron microscopic study of two recent cases of desmoplastic malignant melanoma (DMM) attempts to resolve the conflict in views regarding the nature of the cells responsible for the desmoplasia associated with this clinicopathologic entity. On the basis of evidence presented, it is concluded that the cells are dedifferentiated tumor cells with fibroblastic features and probably functions, rather than host engendered fibroblasts in response to invasive melanoma. The evidence includes: observation of macular desmosomes between tumor cells, an unheralded feature previously noted in amelanotic and melanotic melanomas; electron microscopic observation of fibroblast-like cells by others in spindle cell squamous carcinomas; and light microscopic features of malignancy including vascular invasion in one of the two cases. A reproducible light microscopic pattern diagnosis of this variant of malignant melanoma is reaffirmed in both cases.     

Heat sensitivity and thermotolerance in vitro of human breast carcinoma, malignant melanoma and squamous cell carcinoma of the head and neck

Heat sensitivity and the development of thermotolerance of cells isolated directly from surgical specimens of human breast carcinoma, malignant melanoma and squamous cell carcinoma of the head and neck were studied in vitro using the Courtenay soft agar colony assay. The plating efficiency of some of the tumours was sufficiently high (0.3-20.4%) for survival curves covering up to two to three decades to be established. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. Heat sensitivity of thermotolerant cells was studied by giving cells a conditioning heat treatment of 43.5 degrees C for 60 min and, after incubation at 37 degrees C for 24 h, second graded heat treatments at 43.5 degrees C. Significant differences in heat sensitivity and development of thermotolerance between the three tumour types were not found. However, the heat sensitivity, whether the cells were thermotolerant or not, differed considerably among individual tumours of each histological category. Do at 43.5 degrees C was found to be in the ranges of 23-59 min (breast carcinoma), 20-63 min (malignant melanoma) and 20-57 min (squamous cell carcinoma) for single-heated cells and 105-476 min (breast carcinoma). 102-455 min (malignant melanoma) and 87-400 min (squamous cell carcinoma) for thermotolerant cells. The heat sensitivity of cells made thermotolerant showed no significant correlation to the surviving fraction after the conditioning heat treatment. The study indicated that histological category is a poor parameter for assessment of clinical heat responsiveness of tumours. Breast carcinoma, malignant melanoma and squamous cell carcinoma are probably, from a thermobiological point of view, equally good candidates for clinical trial aimed at studying the potential usefulness of hyperthermia as an adjunct to radiation therapy and/or chemotherapy. The large differences in heat sensitivity and development of thermotolerance observed among individual tumours, irrespective of histological origin, suggested that an in vitro predictive assay for heat responsiveness would be very useful for stratification purposes in such clinical trials.     

Diagnosis of metastatic malignant melanoma by fine needle aspiration biopsy: a clinical and pathologic correlation of 298 cases

Fine needle aspiration biopsies (FNABs) from 298 lesions in patients with suspected metastatic melanoma were studied. The results were correlated either with histopathologic diagnoses on resected lesions or with prolonged clinical follow-up. Of 165 malignant aspirates, 160 were confirmed either by surgical resection (65 cases) or by an appropriate clinical course (95 cases). Of the 107 benign lesions with adequate follow-up, 73 were confirmed as benign. There were 25 false negatives: 19 were inadequate samples, and 6 were presumed failures of needle localization. No interpretative errors were identified. Although 3 cases of FNAB-diagnosed malignant melanoma could not be confirmed by surgical biopsy, the cytologic findings were typical of malignant melanoma. Clinical follow-up, however, suggested that the cytologic diagnosis was in error. One case of a second unrelated malignancy (an adenocarcinoma of the lung) was correctly diagnosed with the use of FNAB. Because of its high degree of accuracy, FNAB has proved useful in the differential diagnosis of subcutaneous nodules, enlarged lymph nodes, and lung nodules.     

Malignant melanoma in a tattoo: case report and review of the literature

Tattooing is a fairly widespread practice worldwide, despite the trauma it entails and the potentially toxic pigments it employs. Several benign and malignant lesions have been described in relation to tattoos, including verrucae, granulomas, basal cell and squamous cell carcinoma. Overall, only 10 cases of malignant melanoma in tattoos are reported in the English literature. We describe a malignant melanoma that developed on a nevus on which a tattoo had been made. The possible pathogenetic relationship between malignant melanoma and tattoos is also discussed.     

Quick diagnosis of malignant melanoma with the touch-fluorescence method during operation

Nine cases of primary melanotic melanoma, three cases of metastatic amelanotic melanoma, and 26 cases of pigmented and unpigmented tumors other than melanoma were examined with the touch-fluorescence method using preparations from the cut surface of the lesions. Fluorescent melanoma cells were easily detected with a fluorescence microscope in all the cases of malignant melanoma whether the melanoma was melanotic or amelanotic. The fluorescent melanoma cells could be divided into three types by configuration: round, spindle-shaped, and pleomorphic. The main cell type of superficial spreading melanoma was round and that of nodular melanoma and acral lentiginous melanoma was chiefly pleomorphic. Fluorescent tumor cells were not seen in pigmented and unpigmented tumors other than melanoma, except in pigmented basal cell epithelioma; this fact made it possible to apply this method routinely for quick diagnosis of malignant melanoma during operation.     

Reasons for the increased incidence of skin cancer

The cutaneous malignancies with an increasing incidence in Japan are squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. As a precancerous state or early lesion, actinic keratoses also deserve attention. According to a nationwide questionnaire survey (responses from 94 centers), basal cell carcinoma has the highest incidence and accounts for nearly 50% of all skin malignancies, followed by squamous cell carcinoma (31%) and malignant melanoma (21%). The number of cases of each tumor has grown annually, and comparison of the percent increases between 1987 and 2001 shows an increase of about 1.5-fold for basal cell carcinoma or 1.7-fold for squamous cell carcinoma or malignant melanoma. Supported by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare, the Malignant Skin Tumor Research Group has been investigating the factors behind these increases by detailed statistical analysis of data obtained from 1987 onwards from designated centers (19-22 centers). Numerous factors have been suggested by this research, but the most important was concluded to be ultraviolet radiation.     

Primary amelanotic malignant melanoma of the vagina--a case report

A case of a primary amelanotic melanoma of the vagina is reported. The patient was a 58-year-old Japanese female. A polypoid tumor was found on the lateral wall of the vagina and a cytologic examination of a scraping showed a few large atypical cells with cleaved nuclei and intranuclear vacuoles. A lateral junctional spread was histologically observed and stage II melanosomes were found in the cytoplasm. Two years after a radical operation, the patient died of a widespread melanotic metastases. The authors survey the number of incidences of malignant melanoma in the female genital organ. In Japanese women, melanoma is seen more frequently in the vagina than in the vulva, which is quite the opposite in cases of malignant melanomas of the genital organs in women of the United States and Europe.     

Metastasis to the iris in squamous cell lung cancer

A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly, she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be derived from squamous cell carcinoma of the lung.     

Fine-needle aspiration of metastatic nonlymphomatous tumors to the major salivary glands: a clinicopathologic study of 40 cases cytologically diagnosed and histologically correlated

BACKGROUND: Metastatic tumors to the salivary glands are common, but documentation in the cytologic literature has been limited. The current study presents the authors' experience with fine-needle aspiration (FNA) in metastatic nonlymphomatous tumors to the salivary glands. METHODS: From a retrospective review of 1675 salivary gland lesions (1535 patients), the authors collected 40 salivary gland lesions (39 patients who had histories of extrasalivary cancer) that were diagnosed cytologically as metastases to the salivary glands and were correlated histologically. RESULTS: FNAs of 34 parotid gland and 6 submandibular gland tumors were performed. The cytologic diagnoses of metastases of squamous cell carcinoma (15 cases), melanoma (12 cases), carcinoma (5 cases), rhabdomyosarcoma (3 cases), and retinoblastoma (2 cases) were confirmed (95%) histologically. Two (5%) FNAs were false-negative. CONCLUSIONS: In patients who had a history of extrasalivary cancer, cytology examination was very helpful and sufficient for adequate patient management.