Cytopathology of oncocytic carcinoid tumor of the lung mimicking granular cell tumor. A case report

BACKGROUND: The cytopathologic features of oncocytic carcinoid tumor of the lung, a rare variant of carcinoid tumor that is composed exclusively of oncocytes, have not been described before in detail. CASE: The bronchial brush smears from an 80-year-old female with an endobronchial obstructive tumor showed single and loose clusters of tumor cells with abundant granular, eosinophilic cytoplasm. The differential diagnoses included oncocytic carcinoid tumor, granular cell tumor, other oncocytic tumors of bronchial origin and metastatic oncocytic tumors. Immunocytochemistry and electron microscopy confirmed the diagnosis of oncocytic carcinoid tumor. CONCLUSION: Oncocytic carcinoid tumor of the lung has cytopathologic features similar to those of granular cell tumor and pulmonary oncocytoma. Immunocytochemistry, electron microscope or both are necessary to distinguish these neoplasms.     

Oncocytic carcinoma of the parotid gland. A case report

BACKGROUND: Oncocytic carcinoma is a rare malignant tumor of the salivary gland. Abundant, granular, eosinophilic cytoplasm is recognized as an oncocytic feature that reflects an accumulation of mitochondria. Ultrastructural study or immunohistochemical staining using antimitochondrial antibody can confirm the oncocytic nature of the tumor. However, there have been no data on whether immunocytochemical staining for human mitochondria aids in the confirmation of the oncocytic nature of oncocytic carcinoma. CASE: A 61-year-old man presented with a swelling in the left lower cheek. Computed tomography demonstrated a solid, isodense tumor in the parotid gland. An excisional biopsy of the tumor was performed, and an enlarged regional lymph node was removed. Imprint cytology of the lymph node showed cohesive cell clusters with lymphocytes. The clusters were composed of tumor cells that had characteristic abundant, granular cytoplasm and round to oval, centrally or eccentrically located nuclei with increased, fine chromatin and distinct nucleoli. Immunocytochemical staining revealed granular immunoreactivity of the cytoplasm for human mitochondria. Histology demonstrated tumor invasion in the normal gland and adjacent skeletal muscles. All tumor cells showed positive cytoplasm with antimitochondrial antibody by immunohistochemistry. Ultrastructural studies demonstrated packed mitochondria in the cytoplasm of the tumor. CONCLUSION: Immunocytochemical staining for human mitochondria help confirm the oncocytic nature of oncocytic carcinoma in cytologic specimens.     

Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology

BACKGROUND: Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). CASE: A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. CONCLUSION: Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.     

Rat renal carcinogenesis after chronic simultaneous exposure to lead acetate and N-nitrosodiethylamine

Chronic oral administration of lead acetate and/or N-nitrosodiethylamine to rats produces three different types of renal cell tumors composed of basophilic, chromophobic or oncocytic cells. The most frequent tumor, often visible macroscopically, is made up of basophilic cells and forms tubular, cystic, pseudo-papillary or solid structures; it may show considerable cellular atypia but does not metastasize or invade the surrounding parenchyma. Chromophobic and oncocytic tumors are rare and can only be detected with the microscope; they usually form cystic or solid structures. Basophilic and chromophobic tumors arise from specific segments of the proximal tubules, characteristic for each carcinogen: P2, P3C and P3M for lead acetate; P2 and P3C for N-nitrosodiethylamine. Karyomegalia in proximal tubule cells appears to be irrelevant in renal carcinogenesis. However, the appearance of basophilic and chromophobic cells in P2, P3C and P3M segments is considered to be an early change in tumor development. Oncocytic microadenomas originate from collecting ducts showing focal oncocytic transformation. Synergistic or inhibitory effects are not observed after chronic simultaneous administration of lead acetate and N-nitrosodiethylamine, although both carcinogens act in common on P2 and P3C proximal tubule segments.     

Mitochondrial Dynamics Protein Drp1 Is Overexpressed in Oncocytic Thyroid Tumors and Regulates Cancer Cell Migration

Oncocytic cell tumors are characterized by the accumulation of morphologically abnormal mitochondria in their cells, suggesting a role for abnormal mitochondrial biogenesis in oncocytic cell transformation. Little is known about the reason for the dysmorphology of accumulated mitochondria. The proteins regulating the morphology of mitochondria, the "mitochondria-shaping" proteins, can modulate their size and number; however, nothing is known hitherto about a possible involvement of mitochondrial dynamics in oncocytic cell transformation in tumors. Our aim was to assess the status of the mitochondria morphology and its role in oncocytic cell transformation. We therefore evaluated the expression pattern of the main mitochondrial fusion and fission proteins in a series of thyroid cell tumor samples, as well as in thyroid tumor cell lines, with and without oncocytic cell features. The expression of mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1 and Fis1) proteins were evaluated by immunohistochemistry (IHC) in a series of 88 human thyroid tumors. In vitro studies, for comparative purposes and to deepen the study, were performed using TPC1 - a papillary thyroid carcinoma derived cell line—and XTC.UC1, an oncocytic follicular thyroid carcinoma-derived cell line. Both IHC and in vitro protein analyses showed an overall increase in the levels of "mitochondrial-shaping" proteins in oncocytic thyroid tumors. Furthermore, overexpression of the pro-fission protein Drp1 was found to be associated with malignant oncocytic thyroid tumors. Interestingly, genetic and pharmacological blockage of Drp1 activity was able to influence thyroid cancer cells’ migration/invasion ability, a feature of tumor malignancy. In this study we show that unbalanced mitochondrial dynamics characterize the malignant features of thyroid oncocytic cell tumors, and participate in the acquisition of the migrating phenotype.     

Cytologic and histologic findings in multiple renal hybrid oncocytic tumors in a patient with Birt-Hogg-Dubé syndrome: a case report

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant neoplastic syndrome characterized by multiple skin lesions, lung cysts and renal tumors. A variety of histologic types of renal tumors have been reported, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma and a recently described hybrid oncocytic tumor, which is thought to be highly associated with BHD. CASE: We report a case of a 48-year-old woman with BHD who initially presented to our institution with spontaneous pneumothorax and was found to have multiple lung cysts and renal tumors on computed tomography. We describe the fine needle aspiration findings of one of the renal tumors, which was suggestive of so-called hybrid oncocytic tumor. We also describe the gross and histologic findings of the multiple kidney tumors that the patient subsequently had excised. CONCLUSION: When multiple kidney tumors from a single patient appear oncycytic on fine needle aspiration, especially when focal clear cells are present, the possibility of oncocytomas and hybrid tumors associated with BHD must be entertained.     

Can abundant colloid exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration? Cytohistological correlation of 127 oncocytic (Hürthle cell) lesions

Objective:  The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. Methods:  Over a 17‐year period, 127 hypercellular, oncocyte‐exclusive, lymphocyte‐absent aspirates obtained via ultrasound‐guided FNA with on‐site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. Results:  Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. Conclusions:  A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA.     

Primary hepatic carcinoid tumor

Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.     

Primary squamous cell carcinoma of the thyroid diagnosed by fine needle aspiration cytology. A report of two cases.

BACKGROUND: Primary squamous cell carcinoma of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. CASES: Two males aged 65 and 68 years presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically malignancy was suspected. Fine needle aspiration (FNA) revealed numerous clusters and isolated malignant cells, dyskeratotic cells and deposits of eosinophilic granular keratin material. Subtotal thyroidectomy was performed. Histologic findings confirmed the cytologic diagnosis of squamous cell carcinoma. CONCLUSION: Primary squamous cell carcinoma of the thyroid is a rare tumor. FNA findings of this tumor were not reported before. FNA study cannot help to differentiate primary from metastatic squamous cell carcinoma of the thyroid.     

Diagnosis of gastric glomus tumor by endoscopic ultrasound-guided fine needle aspiration biopsy. A case report with cytologic,histologic and immunohistochemical studies

BACKGROUND: The majority of glomus tumor are small, benign neoplasms that arise from modified smooth muscle cells. They usually occur in the dermis or subcutis of the extremities. However, rare cases have been reported in the visceral locations, most often in the stomach. CASE: A 32-year-old woman presented with episodes of right upper quadrant pain. She was found to have a gastric tumor that was biopsied at another hospital, where the diagnosis of gastrointestinal stromal tumor (GIST) was made. Endoscopic ultrasound (EUS) performed at our institution revealed a gastric submucosal tumor that was then biopsied by fine needle aspiration (FNA). Cytology revealed cohesive clusters of uniform, round, small cells with ill-defined cytoplasmic borders and scanty, amphophilic cytoplasm. Nuclei were round, with smooth nuclear membranes and evenly distributed, dusty chromatin. Intermingled with those epithelioid cells were small, short, spindled, normal endothelial cells. Immunohistochemical studies performed on cell block showed that the tumor cells were negative for CD34, CD117, chromogranin, synaptophysin, desmin and AE1/AE3 and were strongly positive for SMA, HHF-35 and collagen type IV. Glomus tumor was diagnosed and later confirmed by histology. CONCLUSION: EUS-guided FNA biopsy is efficient and permits adequate sampling for accurate diagnosis of gastric glomus tumor. Although rare, glomus tumor should be in the differential diagnosis among other gastric lesions, such as well-differentiated adenocarcinoma, epithelioid GIST and carcinoid tumor.     

Bronchial granular-cell tumor. Report of a case with preoperative cytologic diagnosis on bronchial brushings and immunohistochemical studies

A 42-year-old man presented with a polypoid endobronchial mass of the right apical segmental bronchus. Bronchial brushing smears contained clusters of cells exhibiting abundant diffusely granular cytoplasm with indistinct borders. A cytologic diagnosis of granular-cell tumor was rendered. Histologic examination of the upper right lobectomy specimen provided confirmation. Immunohistochemically, the granular cells strongly reacted with the S-100 protein antibody. This case demonstrates that the cytologic diagnosis of bronchial granular-cell tumor is possible if this lesion is considered in the differential diagnosis of lung tumors.     

Multifocal nodular oncocytic hyperplasia in parotid gland: a case report

BACKGROUND: Multifocal nodular oncocytic hyperplasia (MNOH) is a rare lesion of the parotid gland. Fine needle aspiration cytology (FNAC) in MNOH has not been described previously to the best of our knowledge. CASE: A 55-year-old woman presented with a lump at the left angle of her mouth for 2 months. Local examination revealed a hard, nontender parotid mass. FNAC revealed clusters as well as discretely lying oncocytic cells. cells at places showed moderate nuclear pleomorphism. The features were consistent with a diagnosis of oncocytic neoplasm neoplasm; however, because of pleomorphism, a suspicion of carcinoma was offered. The patient underwent superficial parotidectomy, and histopathology examination revealed it to be multifocal nodular oncocytic hyperplasia. CONCLUSION: MNOH is a rare nonneoplastic salivary gland lesion and should be considered in the differential diagnosis of oncocytic neoplasm on FNAC.     

Fine needle aspiration cytology of mixed medullary-follicular thyroid carcinoma: a case report

BACKGROUND: Mixed medullary-follicular thyroid carcinoma (MMFTC) is a rare tumor that has been regarded as a clinicopathologic variant of medullary thyroid carcinoma. MMFTC represents a diagnostic challenge by fine needle aspiration cytology (FNAC). CASE: A 77-year-old woman had a palpable mass on the left side of the neck. It was diagnosed as follicular neoplasm by FNAC; she underwent total thyroidectomy. Pathology revealed follicular carcinoma. Radioactive iodine was administered. An enlarging mass was present in the left mandible later. FNAC showed suspicious follicular neoplasm with predominance of oncocytic cells. Pathology revealed follicular carcinoma with parafollicular cell differentiation. Immunohistochemical analysis demonstrated positive status for thyroglobulin and calcitonin. Simultaneous expression of thyroglobulin and calcitonin within the same neoplastic cell was considered. She underwent several courses of radioactive iodine therapy without significant effect. Interestingly, her serum calcitonin level was not elevated. CONCLUSION: Coexpression of thyroglobulin and calcitonin in the same cell is very rare. The component of medullary carcinoma should be considered when encountering an atypical thyroid carcinoma with predominance of cells showing oncocytic changes on FNAC and with clinically poor response to conventional treatment. Immunohistochemistry and pathologic analyses are helpful to confirm the diagnosis, especially in the absence of elevated serum calcitonin level.     

Receptors for gastrin on gastric carcinoid tumor membrane of Mastomys natalensis

Specific binding sites for human gastrin I (gastrin) were identified in a crude membrane preparation from the gastric carcinoid tumor of Mastomys (Praomys) natalensis. The binding of 125I-gastrin to the carcinoid tumor membrane was saturable, and Scatchard analysis of the data revealed a single class of binding site with a dissociation constant of 139.2 pM and a maximal binding capacity of 23.5 fmol/mg protein. Gastrin and CCK8 equipotently and dose-dependently displaced the binding of 125I-gastrin to the membrane. GTP but not ATP decreased 125I-gastrin binding to the membrane, and removal of Mg2+ attenuated this inhibitory action of GTP. The GTP-induced reduction of 125I-gastrin binding was found to be due to a decrease in binding affinity without a change in binding capacity. These results clearly indicate the presence of specific binding sites for gastrin, probably coupled to guanine nucleotide-binding protein, in the carcinoid tumor membrane of Mastomys, and suggest that gastrin has possible biological actions on these tumors.     

Fine needle aspiration cytology of pulmonary carcinoid tumors

Twenty-four cases coded as pulmonary carcinoid tumors initially sampled by fine needle aspiration (FNA) biopsy were reviewed in order to determine the cytologic features most useful in making the FNA diagnosis. The diagnosis of carcinoid tumor had been confirmed in 23 cases; the remaining case, though closely resembling a carcinoid tumor on the FNA specimen, proved to be a sclerosing hemangioma of the lung. Comparison of the original and review interpretations of the FNA specimens revealed that all typical spindle cell carcinoids and all atypical carcinoids were correctly diagnosed and classified. Of the 15 typical round cell carcinoids, the original cytologic diagnosis was lymphoma in 2 cases and benign bronchial lining cells in 2 cases. Thus, it appears that diagnostic errors are most likely in "typical" carcinoids. Review of the FNA findings suggests that the frequently stripped cytoplasm (with resulting non-cohesive bare nuclei), coupled with the almost universal plexiform vascularity (seen in 21 of 23 cases), should allow an accurate cytologic diagnosis in virtually all cases.     

The value of multiple preparations in the diagnosis of malignant pleural effusions. A cost-benefit analysis

A cost-benefit analysis of five techniques employed in processing 108 malignant pleural effusions for cytopathologic examination was performed. Ethanol-fixed, Papanicolaou-stained smears were positive in 68% of the effusions, air-dried Diff-Quik-stained smears in 66%, Cytospins in 83%, cell blocks in 85% and Millipore filters in 85%. Examination of one air-dried smear and one ethanol-fixed smear yielded a diagnostic sensitivity of 82%. Using a combination of two smears and one of three concentrating techniques (Cytospin, cell block or MIllipore filter) would have provided a diagnosis in over 90% of the effusions. The use of four or more preparations provided more sensitivity than did three preparations and decreased the likelihood that a malignant diagnosis would be based on the findings in only one preparation. The costs related to disposable materials and the College of American Pathologists (CAP) work load estimates for specimen preparation, staining and screening were compared. These data may be useful in developing optimal protocols for pleural effusion preparation in laboratories with specific work load requirements and limited resources.     

Liquid-based cytology findings of glassy cell carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis

BACKGROUND: Glassy cell carcinoma is a rare form of poorly differentiated carcinoma of the cervix with no obvious squamous or glandular differentiation. Its liquid-based cytology findings have not been described before. CASE: A 46-year-old Filipina presented with vaginal bleeding due to a bulky cervical tumor. The liquid-based cytology preparation was of moderate cellularity and contained small clusters of polygonal to elongated tumor cells admixed with amphophilic, granular, necrotic debris. The malignant cells possessed round to oval nuclei; a thin nuclear membrane; finely dispersed chromatin; prominent, solitary nucleoli; abundant, cyanophilic cytoplasm; and discrete cell borders. Occasional tumor cells showed phagocytosis of polymorphs. The background contained a mixed population of inflammatory cells. Eosinophils, though present, were not readily identified in the cytologic specimen. There was no evidence of dyskeratosis, cytoplasmic vacuolation or koilocytosis. Histologic and ultrastructural examination of the tumor biopsy showed classic features of glassy cell carcinoma. Molecular analysis using polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus (HPV) DNA in the liquid-based cytology sample. The HPV genotype, however, did not belong to any of the commonly encountered prototypes. CONCLUSION: Glassy cell carcinoma of the cervix may show distinct, though subtle, cytomorphologic features in liquid-based preparations. The findings, however, are slightly different from those in conventional cervical smears. Awareness of this rare entity is important, as glassy cell carcinoma is often associated with more aggressive clinical behavior.     

Aspiration biopsy cytology of benign clear cell ("sugar") tumor of the lung

Benign clear cell tumor (BCCT) of the lung is an uncommon neoplasm, with about 24 cases reported in the literature. A fine needle aspirate from a histologically and ultrastructurally confirmed BCCT of the lung contained large irregular clusters of polygonal and spindle-shaped benign-appearing cells with vacuolated, granular, periodic-acid-Schiff-positive cytoplasm. Cytologic study of the aspirate suggested a pseudoinflammatory tumor; however, a metastatic renal cell tumor or a primary clear cell or mesenchymal tumor could not be excluded. The histologic, ultrastructural and cytochemical findings are also presented, and the cytologic differential diagnosis of this neoplasm is briefly discussed.     

Granular cell ameloblastoma of the jaw. A report of two cases with fine needle aspiration cytology

BACKGROUND: Fine needle aspiration cytology (FNAC) of jaw tumors has not been studied extensively. Ameloblastomas are jaw tumors that show a wide morphologic spectrum and thus may pose some diagnostic difficulties. Of the many types, granular cell ameloblastoma (GCA) is an uncommon variant that possesses distinctive features. To the best of our knowledge, there have been no previous reports on the cytologic findings of GCA. We present two cases diagnosed by FNAC. CASES: Two cases of GCA were diagnosed on cytology and subsequently confirmed on histology. Both patients presented with a large, lytic jaw tumor. FNAC smears showed characteristic granular cells along with spindle and basaloid cells. CONCLUSION: Although GCAs are rare tumors, they possess distinctive features that permit an accurate diagnosis, provided that this entity is kept in mind. This tumor has to be differentiated from cystic odontogenic lesions, epulis and granular cell myoblastoma. An accurate preoperative diagnosis also helps the surgeon to plan more extensive surgery as these tumors show a great propensity for malignant change and metastases.     

Comparison of CD15, galectin-3 and HBME-1 expression in follicular thyroid neoplasms

INTRODUCTION: Estimation of malignancy in thyroid follicular neoplasms is a common diagnostic problem, thus revealing of differences in expression of some antigens in both benign and malignant lesions seems to be essential. The aim of this study is to evaluate the immunohistochemical expression of CD15, galectin-3 and HBME-1 in follicular adenomas and carcinomas. MATERIAL AND METHODS: Samples of 38 follicular adenomas (23 "classical", 5 with intracapsular invasion, 10 oncocytic) and 15 follicular carcinomas (9 "classic", 6 oncocytic) were stained immunohistochemically with anti-CD15, galectin-3 and HBME-1. RESULTS: In the whole group we found statistically significant differences in CD15 expression between follicular adenomas and carcinomas. "Classic" follicular carcinomas (without oncocytic tumors) showed stronger CD15 and HBME- 1 expression than "classic" adenomas. Adenomas with intracapsular invasion differed from "classic" adenomas only in HBME-1 expression. In oncocytic tumors the expression of examined antigens was similar. CONCLUSIONS: 1. In the group of nonoxyphilic tumors positive reaction with HBME-1 was more common in adenomas with intracapsular invasion and carcinomas, but positive reaction with anti-CD15--only in carcinomas. We suggest that reactivity with these antibodies could mark malignancy. 2. Oncocytic tumors had similar expression of CD15 and HBME-1 and galectin-3.