Macrofollicular encapsulated variant of papillary thyroid carcinoma as a potential pitfall in histologic and cytologic diagnosis. A report of three cases

BACKGROUND: Macrofollicular encapsulated papillary carcinoma (MEPC) is a variant of papillary carcinoma with a favorable clinical course. Its characteristic histologic pattern could be mistaken for that of an adenoma or hyperplastic nodule. Fine needle aspiration of this neoplasm may not show the particular nuclear features of papillary carcinoma, so the cytologic diagnosis may be benign. CASE REPORTS: Three paradigmatic cases of MEPC with different histologic patterns, diagnosed as a follicular neoplasm using fine needle aspiration biopsy (FNAB) are described. Preoperative cytology showed scattered clusters of thyrocytes with prominent nuclear pleomorphism and irregularities and focal oxyphilic changes mixed with colloid and aggregates of typical thyrocytes. The histologic picture exhibits small, neoplastic foci showing a microfollicular structure within an encapsulated neoplasm with a macrofollicular pattern. In microfollicular areas obvious nuclear pseudoinclusions were seldom observed. CONCLUSION: MEPC represents a challenging tumor subtype that infrequently shows the pathognomonic cytologic characteristics of papillary carcinoma, and therefore it is much more difficult to diagnose with a FNAB. Nuclear pleomorphism and irregularity of the nuclear membrane of thyrocytes are clues to this variant, although in some cases a clear-cut preoperative diagnosis cannot be made.     

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the thyroid. A case report

BACKGROUND: Although mucoepidermoid carcinoma is considered a very rare, low grade thyroid neoplasm, in two patients a very rapid and aggressive outcome occurred. We describe the cytologic, histologic and immunohistochemical findings of a high grade mucoepidermoid carcinoma that evolved into an anaplastic carcinoma. CASE: A 57-year-old man was admitted with dysphagia, dysphonia and odynophagia. The patient had begun to develop symptoms over the previous two months. Ultrasound and computed tomography revealed diffuse enlargement of the thyroid gland with multiple, bilateral, palpable lymph nodes in the cervical, supraclavicular, paratracheal and retrocaval chains. The patient died four weeks after receiving the first cycle of treatment with adriamycin and cisplatin. The smears were highly cellular, with a background rich in neutrophilic, inflammatory infiltrate and necrotic debris. Two main types of tumor cell were identified: squamoid and mucus secreting. Squamoid cells were polygonal, with well-defined borders and dense cytoplasm. Nuclei varied greatly in shape and size and displayed clumped chromatin and prominent nucleoli. Mucussecreting cells were ring shaped and dispersed among the squamoid cells; they contained a large vacuole, with condensed acid and neutral mucins, that peripherally displaced the nucleus. Small and large clusters of large, polygonal cells with single or multiple bizarre nuclei and less-dense cytoplasm were also present. Histology revealed tumor cells distributed in irregular nests, with necrosis surrounded by a fibrous stroma. The predominant cells were squamoid, but dispersed mucus-secreting cells were frequently seen in the better-differentiated areas. Sparse anaplastic spindle cells were observed adjacent to the squamoid focus. Immunohistochemistry revealed a reaction positive for cytokeratin (AE3/AE1) in tumor nests and negative staining for thyroglobulin and neuroendocrine markers. CONCLUSION: Although mucoepidermoid carcinoma of the thyroid is a very rare neoplasm, its peculiar cytomorphologic features in fine needle aspiration cytology may contribute to its correct diagnosis.     

Neuroendocrine (Merkel-cell) carcinoma of the skin. Fine needle aspiration cytology and clinicopathologic study of a case

Neuroendocrine (Merkel-cell) carcinoma of the skin, a neoplasm usually found in elderly individuals, is often locally aggressive and has the potential to metastasize to lymph nodes and cause death. Microscopically the neoplasm is a small-cell carcinoma that involves primarily the dermis. We report a case of such a neoplasm in a 61-year-old female, stressing the possible contribution of fine needle aspiration cytology in the recognition of this neoplasm and its differentiation from other small-cell neoplasms that may involve the skin.     

Fine needle aspiration cytology diagnosis of renal medullary carcinoma: a case report

BACKGROUND: Renal medullary carcinoma is a recently described, highly aggressive neoplasm that affects predominantly young African American males with a history of sickle cell trait. To the best of our knowledge, this is the first report of fine needle aspirate cytology (FNAC) findings of renal medullary carcinoma. CASE: A 14-year-old, African American male with a history of sickle cell trait presented with the sudden onset of third cranial nerve palsy. Radiographic examination demonstrated possible tumor masses in the brain, thorax and left kidney. Ultrasound-guided fine needle aspiration was performed on the left kidney, and a cytologic diagnosis of "suspect renal medullary carcinoma" was rendered. The cytologic diagnosis was confirmed by tissue examination. CONCLUSION: The cytologic features of renal medullary carcinoma include loosely cohesive clusters and single epithelioid cells with cytologic atypia, including high nuclear/cytoplasmic ratios, hyperchromasia, prominent nucleoli and cytoplasmic vacuolation. These cytologic findings, coupled with clinical findings (young black male with sickle cell trait), allow recognition of this rare renal neoplasm.     

Pilomatrical carcinoma

Pilomatricoma is a common benign skin-appendage tumor. Surgeons should be on the alert for pilomatrical carcinoma, an aggressive variation of a usually benign skin neoplasm.     

Thin-layer (liquid-based) cytologic findings of papillary squamotransitional cell carcinoma of the cervix. Review of cases over a 4-year period with emphasis on potential diagnostic pitfalls

OBJECTIVE: To describe the thin-layer cytology and diagnostic pitfalls of papillary squamotransitional cell carcinoma of the cervix, with clinical and histologic correlation. STUDY DESIGN: The author reviewed the clinical findings, thin-layer cytology and histologic features of papillary squamotransitional cell carcinoma of the cervix encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period January 1998-March 2002. Strict histologic criteria (basaloid/transitional cell-like cells constituted > 70% of the tumor cell population and papillary/anastomosing, frondlike structures seen in > 70% of tumor tissue in superficial biopsies) were employed in defining this entity. RESULTS: During the study period, 10 biopsy cases of carcinoma of the lower female genital tract (9 in cervix and 1 in vagina) fulfilled the above histologic criteria. Six of them had thin-layer cytology performed The preparations were often of moderate to high cellularity and contained three-dimensional, arborizing, papillary clusters of basal/parabasal cells. Discernible fibrovascular cores were sometimes identified. Occasionally at the papillary surface, the basaloid cells were aligned horizontally. High-power cytology of the tumor cells ranged from bland-looking to high grade squamous intraepithelial lesions (HSILs) and sometimes squamous cell carcinoma. Mitotic figures were commonly identified. Tumor diathesis and dyskeratotic cells were occasional. Koilocytosis was not observed. Subsequent tumor biopsies showed evidence of stromal invasion in 3 cases. CONCLUSION: Papillary squamotransitional cell carcinoma has a distinctive appearance in thin-layer cytologic preparations. The predominance of bland-looking basaloid cells or HSIL cells, together with scantiness of tumor diathesis and carcinoma cells, may lead to underdiagnosis. Recognition of the subtle cytologic features and clinical correlation are essential in arriving at a correct diagnosis.     

Fine needle aspiration cytology of metastatic hepatic adrenocortical carcinoma mimicking hepatocellular carcinoma: a case report

BACKGROUND: Adrenocortical carcinoma (AC) is a rare neoplasm, usually considered one of the most morbid and lethal human tumors. It occurs primarily in children and young adults and often presents with advanced and/or metastatic disease. CASE: A 9-year-old boy with a previous diagnosis of adrenocortical carcinoma underwent computed tomography (CT)-guided fine needle aspiration (FNA) for preoperative investigation of a hepatic mass. All smears revealed abundant groups of cells surrounding an interconnective, thin-walled, central vascular core. These cells showed finely vacuolated, large cytoplasm with eccentrically placed nuclei. Occasionally, cells underwent a sudden, marked increase in size, with prominent atypia. Multinucleated, atypical giant cells and high mitotic rate were also evident. The cytologic findings resembled the previous histologic adrenocortical carcinoma features. CONCLUSION: The cytologic features of metastatic hepatic adrenocortical carcinoma may mimic those of hepatocellular carcinoma. However, the presence of atypical multinucleated and pleomorphic cells with microvacuolated cytoplasm and eccentric nuclei as well as the absence of naked nuclei and endothelial linings yield the diagnosis of adrenocortical carcinoma. Nevertheless, other space-occupying liver lesions in children must also be considered. This case demonstrates the usefulness of CT-localized FNA biopsy in hepatic masses in children, and discusses the possible cytologic differential diagnosis.     

Cytomorphology of primary small-cell (Merkel-cell) carcinoma of the skin in fine needle aspirates

The histologic appearance of primary small-cell carcinoma of the skin (the so-called Merkel-cell tumor) is similar to other small-cell tumors that may metastasize to the dermis. Significance has been placed on the electron microscopic appearance of this tumor since the ultrastructural features of this neoplasm are helpful in distinguishing it from most of the other neoplasms considered in the differential diagnosis. To determine whether any additional morphologic criteria might exist to distinguish this neoplasm, the fine needle aspirate appearance of a primary small-cell carcinoma of the skin was studied and compared to that of similar preparations of other small-cell tumors that could potentially involve the dermis. Cells of this unusual tumor were round and showed neither cohesiveness nor nuclear molding. Mitoses were numerous. The chromatin pattern was bland. The cytologic features of this tumor can aid in the distinction of primary small-cell carcinoma of the skin from other metastatic small-cell neoplastic lesions in the dermis of adults.     

Fine needle aspiration cytology of invasive micropapillary (pseudopapillary) carcinoma of the breast. Report of 11 cases with clinicopathologic findings

OBJECTIVE: To describe the cytologic features of invasive micropapillary carcinoma of the breast, a distinct, unusual variant of infiltrating duct carcinoma characterized histologically by pseudopapillary structures lacking fibrovascular cores and tubuloalveolar structures floating freely within clear spaces separated by a delicate fibrocollagenous stroma and characterized clinically by prominent lymphotropism and an aggressive clinical course. STUDY DESIGN: We reviewed the clinical, cytologic, histologic, immunohistochemical and flow cytometric features in 11 cases of invasive micropapillary carcinoma of the breast diagnosed preoperatively by fine needle aspiration. RESULTS: All patients were women, ranging in age from 31 to 83 years. A preoperative diagnosis of malignancy was made in all cases. Tumor size ranged from 1.2 to 5.5 cm. Ten patients had lymph node metastases. Cytology was characterized by a "dual" pattern formed by round or angulated, three-dimensional, cohesive clusters of neoplastic cells with pseudopapillary configuration and two-dimensional, dyscohesive aggregates and single cells with high grade nuclei and intact cytoplasm.     

Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.     

Asymptomatic intrathyroidal parathyroid adenoma. Report of a case with a cytologic differential diagnosis including thyroid neoplasms

BACKGROUND: Intrathyroidal parathyroid neoplasms (IPNs) are uncommon tumors with an indolent clinical course. When asymptomatic, they can be incorrectly diagnosed as thyroid neoplasms on fine needle aspiration biopsy (FNAB), leading to inappropriate surgical treatment. CASE: A case of unsuspected IPN occurred in which the cytologic picture mimicked that of a thyroid neoplasm. The histologic specimen of the total thyroidectomy showed 2 adjacent intrathyroidal nodules morphologically and immunohistochemically corresponding to a parathyroid adenoma. CONCLUSION: The incidence of IPN remains controversial, especially in asymptomatic patients. On FNAB it is a possible cause of inappropriate surgery for a suspicious thyroid neoplasm (follicular or medullary carcinoma). Immunostaining for parathormone on the cytologic smear is valuable in establishing the correct preoperative diagnosis when the morphologic features are strongly suggestive of IPN.     

Molecular pathology in the diagnosis and treatment of non-Hodgkin's lymphomas

The non-Hodgkin's lymphomas encompass a wide spectrum of hematologic neoplasms that exhibit different clinical and biological features. Lymphomas classically have been initially assessed based on their cytologic and histologic features. Morphology alone is often inadequate as similar appearing neoplasms may be immunophenotypically and molecularly heterogeneous. Molecular diagnostic methods can provide an additional level of testing that not only helps refine diagnoses but can provide prognostic information. New methods are being refined that may provide information to establish precise diagnostic profiles, provide targets for therapy and provide more sensitive methods for monitoring the success of treatment. Molecular methods will be increasingly utilized and eventually required as the accepted method of diagnosis and for monitoring the disease. Understanding of the molecular abnormality and the pathogenesis of the neoplasm hopefully will lead to therapeutic intervention aimed at the specific molecular defect or its product. The molecular pathology of the non-Hodgkin's lymphomas is discussed.     

Cytomorphologic features of Merkel cell carcinoma in fine needle aspiration biopsies. A study of two atypical cases

OBJECTIVE: To report atypical cytomorphologic features in fine needle aspiration biopsies (FNABs) from two cases of Merkel cell carcinoma (MCC), a primary neuroendocrine neoplasm of skin. STUDY DESIGN: Retrospective review of FNABs with histologic correlation from six patients with MCC and a report of findings from two whose smears showed atypical features. RESULTS: Typically the aspirates produce highly cellular smears of loosely clustered and individual, relatively monomorphic, small tumor cells with round to oval, regularly contoured nuclei. In two of our cases, the tumor cell nuclei exhibited a spectrum of pleomorphism ranging from moderately complex nuclear membranes with cleaves, indentations and protrusions in one case to large, markedly bizarre, convoluted nuclei and multinucleate tumor cells in the extreme case. Both cases were primary neoplasms, and the diagnosis was based on clinical, histologic and immunohistochemical data. Additionally, electron microscopy was performed on the tumor with bizarre nuclei and demonstrated rare, dense core neurosecretory granules and paranuclear bundles of intermediate filaments.     

Follicular carcinoma of the thyroid with hyperthyroidism. A case report

BACKGROUND: Follicular carcinoma of the thyroid in association with hyperthyroidism is rare. The malignant lesion may remain occult for a long time. Certain clinical and cytologic features may be helpful in raising the alarm. CASE: An elderly male with a history of occupational exposure to X rays, long-standing toxic multinodular goiter and clinical hyperthyroidism presented with a rapidly enlarging mass in the neck. Cytologic smears showed a prominent microfollicular pattern, scanty colloid, anisonucleosis and nuclear overlapping. The noteworthy feature was the presence of marginal vacuoles. The cytologic diagnosis of follicular neoplasm with highly suggestive malignancy was made. Subsequently, multiple pulmonary nodules provided radiologic evidence of possible metastatic spread. CONCLUSION: This case report demonstrates the rare association of follicular carcinoma of the thyroid with hyperthyroidism and analyzes certain high-risk clinical and cytologic features to be considered in the follow-up of long-standing hyperfunctioning multinodular goiter.     

Aspiration cytology in the diagnosis of primary tumors of skin adnexa

OBJECTIVE: To evaluate the cytologic features and pitfalls in the cytodiagnosis of certain tumors of skin adnexa. STUDY DESIGN: Smears from five nodular basal cell carcinomas, two chondroid syringomas and one case each of primary mucinous carcinoma, Merkel cell tumor, trichoepithelioma, pilomatrixoma and eccrine spiradenocarcinoma, all histologically confirmed, were evaluated with special attention to cytologic features that may aid the diagnoses. RESULTS: Ten of 12 (83.3%) adnexal tumors were correctly recognized on aspiration cytology. The five basal cell carcinomas were atypical in presentation and clinically unsuspected but were diagnosed on cytology. The chondroid syringomas and Merkel cell tumor could also be diagnosed due to awareness of the cytologic features and sound clinical correlation. The eccrine spiradenocarcinoma was diagnosed as spiradenoma because of improper assessment of local invasion and incorrect mitotic count in the aspirates. The diagnosis was inaccurate in primary mucinous carcinoma as the aspirate yielded mainly mucin. CONCLUSION: Although exact subtyping of tumors of skin adnexa may not always be essential, certain benign adnexal tumors have aggressive counterparts (e.g., eccrine spiradenomas), while others clinically mimic metastases or small round cell carcinomas (e.g., Merkel cell tumors). Thus, correct cytodiagnoses and awareness of the limitations of cytology (such as in the assessment of local invasion) in these instances help to outline surgical management.     

Microcystic adnexal carcinoma of the scalp treated with surgical resection along with chemoradiation: A case report and review of the literature

Microcystic adnexal carcinoma (MAC) is an infiltrative rare cutaneous neoplasm for which there are no consensus management guidelines because of the paucity of evidence-based practice; hence, the utility of their management is based only on previously published case reports. We report a case of a scalp lesion that was successfully treated using a combination of surgical resection, chemotherapy, and radiotherapy.     

Papillary carcinoma of the common bile duct. Diagnosis by bile drainage cytology

A 54-year-old man with clinical and radiologic findings suggestive of pancreatic carcinoma had cytologic examination of bile drainage fluid specimens prepared by membrane filtration and cytocentrifugation. Examination showed clumps of malignant cells with features most consistent with a well-differentiated papillary neoplasm of bile duct origin, rather than a primary pancreatic carcinoma. Partial pancreatoduodenectomy with resection of the proximal common bile duct confirmed the presence of a small, well-differentiated but invasive papillary bile duct carcinoma. Pancreatic carcinoma and papillary carcinoma of the bile duct are anatomically and biologically different lesions that should be distinguished, when possible, by cytologic examination. In this case, surgical treatment was planned on the assumption that cytologic examination could distinguish a papillary carcinoma of the bile duct from the clinically suspected pancreatic adenocarcinoma.     

Significance of cytologic smears in the diagnosis of small cell carcinoma of the uterine cervix

OBJECTIVE: To provide improved identification of small cell carcinoma (SMCC) and reevaluate the significance of cervical cytologic smears in its diagnosis. STUDY DESIGN: Analyses of histocytologic morphology and clinical data were performed by reviewing clinical records, histopathology and cervical cytology smears from 18 SMCC cases of the uterine cervix (including one recurrent case and three SMCC cases with adenocarcinoma) between 1986 and 2001. RESULTS: Most cases showed minimal cytoplasm, finely stippled ("salt and pepper") chromatin, prominent nuclear molding and smearing effect. Cytologic smears diagnosed or suggested 79% of SMCC cases before histologic confirmation. Of the cases, 89% displayed moderate to high cellularity. The tumor cells were arranged mostly in clusters of varying sizes with no typical architectural pattern. In addition, the tumors often exhibited very pleomorphic cells and recognizable nucleoli. CONCLUSION: Cytologic features of SMCC cells are characteristics enough for specific diagnosis or at least an early indication of it. Timely detection by cervical cytologic smears will allow clinicians to initiate prompt treatment of these aggressive tumors.