Cytological findings of intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation: a study of eight cases

The purpose of this article is to describe the cytologic findings of intrathyroidal epithelial thymoma/carcinoma showing thymus-like differentiation (ITET/CASTLE) in detail and discuss its differential diagnoses. We examined cytologic specimens taken from eight ITET/CASTLE cases, who underwent fine needle aspiration. Cytologic features of ITET/CASTLE include (1) hypercellularity, (2) large cell clusters without papillary or follicular pattern, (3) round or spindle tumor cells with distinct nucleoli and cell border, (4) few keratinized cells and intracytoplasmic lumina (ICL), and (5) lymphocytic background. The differential diagnoses included poorly differentiated carcinoma, metastatic lymphoepithelioma, squamous cell carcinoma, and mucoepidermoid carcinoma. The presence of individual keratinizing cells and ICL and the location of the tumor may be helpful in indicating ITET/CASTLE.     

Carcinoma showing thymus like elements: Report of a case with EGFR T790M mutation

Carcinoma showing thymus‐like differentiation of the thyroid (CASTLE) is a rare tumor involving the thyroid and perithyroidal soft tissues. It shares morphological, immunohistochemical and molecular similarities with thymic carcinomas. Due to its relatively better prognosis, it needs differentiation from other primary and metastatic tumors of this region. A 40‐year‐old lady presented with a gradually progressive anterior neck swelling for one year. Imaging showed bulky right and left lobes of thyroid along with a solid soft tissue mass in the pretracheal region. Fine needle aspiration smears showed features of poorly differentiated carcinoma. Total thyroidectomy with excision of the mass revealed histopathological features characteristic of CASTLE, with evidence of thyroiditis in adjoining thyroid. Epidermal growth factor receptor (EGFR) assay revealed presence of EGFR T790M somatic mutation in exon 20. The same was not detectable on direct sequencing. We present a rare case of CASTLE, occurring in association with Hashimoto thyroiditis, with emphasis on cytological features and report for the first time the presence of a low level somatic mutation in EGFR (EGFR T790M mutation).     

甲状腺呈胸腺样分化癌病理观察

目的 探讨甲状腺呈胸腺样分化癌（CASTLE）的病理特征、诊断及鉴别诊断。方法 分析2例甲状腺CASTLE的临床表现,对标本进行病理学和免疫组织化学（EnVision^TM法）染色观察。结果 大体检查肿瘤呈质硬灰白色略旱分叶状肿块。光镜下肿瘤组织呈轮廓清楚的巢状,巢间可见丰富的促结缔组织增生性间质。肿瘤细胞呈多边形或梭形,胞质轻度嗜酸,核卵圆形,呈空泡状,有清楚的小核仁,核异型性较轻,核分裂象1～2／10HPF。免疫组织化学肿瘤细胞表达CD5及CD117。结论 CASTLE是一种少见的甲状腺恶性肿瘤,有一定的病理学特征。应与甲状腺未分化癌、甲状腺鳞状细胞癌、转移性淋巴上皮瘤样癌及滤泡树突细胞肉瘤等鉴别。免疫组织化学CD5等标记对鉴别诊断有帮助。     

Cytologic features in fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia

Fine-needle aspirates from a sclerosing mucoepidermoid thyroid carcinoma with eosinophilia showed peculiar but nonspecific features. The overall picture seems more important than individual elements in recognizing this rare entity cytologically, since the predominant type of malignant cells has a deceptively bland appearance. The differential diagnoses include other primary thyroid malignancies, as well as metastatic growth and Hashimoto's thyroiditis. Diagn Cytopathol 1996;15:301–305. © 1996 Wiley-Liss, Inc.     

Cytopathology of retrograde renal pelvis brush specimens: An analysis of 40 cases with emphasis on collecting duct carcinoma and low-intermediate grade transitional cell carcinoma

We report our experience with 40 retrograde renal brush samples of pelvic-calyceal lesions with confirmatory tissue studies. On-site cytopathologic evaluation was performed in 38 of these specimens. The final histologic diagnoses included 24 cases of transitional cell carcinoma (TCC), 17 of which were low-intermediate grade tumors. All 24 cases were diagnosed cytologically as TCC (22), or as suspicious for TCC (2). Three cases classified as collecting duct carcinomas were resected; the cytologic specimens in 2 of these cases were interpreted as TCC, and one as reactive change. There were three renal cell carcinomas (RCC); cytologically, one was considered a papillary neoplasm, one suspicious for malignancy, and one as reactive. Two cases of atypical renal cysts were reported as suspicious for malignancy in both cytologic and histologic material. There was one case of metastatic colon carcinoma identified in the brush specimen. Finally, tissue studies in the remaining 7 cases showed reactive/inflammatory changes; however, four of the corresponding pelvic brush specimens were considered abnormal. A review of the above cases is reported with the objective of presenting the cytologic features seen in collecting duct carcinoma, low-intermediate grade TCC, and diagnostically difficult cases with cyto/histomorphologic discrepancies. The contribution of on-site assessment to diagnostic accuracy is also discussed. Diagn Cytopathol 1996;15:312–321. © 1996 Wiley-Liss, Inc.     

Intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation; comparison with thymic lymphoepithelioma‐like carcinoma and a possibility of development from a multipotential stem cell

The purpose of our article is to describe the immunohistochemical findings of intrathyroidal epithelial thymoma/carcinoma showing thymus‐like differentiation (ITET/CASTLE) of the thyroid in detail, to clarify the difference between ITET/CASTLE and thymic lymphoepithelioma‐like carcinoma (LELC), and to discuss the pathogenesis of ITET/CASTLE. We immunohistochemically examined five ITET/CASTLE and eight LELC cases. All of ITET/CASTLE cases were strongly positive for CD5, P63, high‐molecular‐weight cytokeratin and B‐cell CLL/lymphoma‐2. Carcinoembryonic antigen‐positive carcinoma cells were found in four ITET/CASTLE cases. Neuroendocrine marker‐positive carcinoma cells were scattered in all cases. Immunohistochemical findings in thymic LELC were essentially similar to those in ITET/CASTLE, but the sensitivity was different. There is a possibility that ITET/CASTLE and thymic LELC are not the quite same disease entity. We think that ITET/CASTLE is derived from ectopic thymus, but not related to solid cell nests.     

Thyroid carcinoma showing thymus‐like differentiation (CASTLE): Case report with cytomorphology and review of the literature

Thyroid carcinoma showing thymus‐like differentiation (CASTLE) is a rare tumor of the thyroid gland or adjacent soft tissues of the neck. Given the comparatively good prognosis of CASTLE, it is crucial to distinguish this neoplasm from other more aggressive thyroid neoplasms that can have similar or overlapping cytomorphological features. However, there is little information about the cytomorphology of CASTLE available in the literature. Here we report the cytomorphology and histology of thyroid CASTLE in a 52‐year‐old woman and present a review of the literature. Diagn. Cytopathol.2011;39:204–209. © 2010 Wiley‐Liss, Inc.     

Follicular variant of papillary carcinoma of the thyroid: To what extent is fine-needle aspiration reliable?

We have reappraised the fine-needle aspirates (FNAs) of 5 cases of the follicular variant of papillary carcinoma of the thyroid (FVPCT). Three of these had been performed on cold thyroid nodules and had been diagnosed as follicular proliferations. The remaining 2 had been performed on cervical lymphadenopathies and had been diagnosed as metastatic papillary carcinoma, probably of thyroid origin. Careful reassessment of the slides did not allow any change of the original diagnoses. We found two constant cytologic features present in all cases studied; syncytial clusters without acinar formation, and monolayered sheets. Nonconstant findings included: follicular pattern, ropy colloid, multinucleated giant cells (MGCs), and nucleoli in FNAs performed on thyroid nodules, and papillae, pseudonuclear inclusions, nuclear grooves, MGCs, and nucleoli in FNAs performed on cervical lymphadenopathies. Our findings suggest that the cytologic diagnosis of FVPCT is very difficult if based solely on the cytologic features seen in FNAs, and that it is necessary to resort to the study of surgical specimens if a definitive diagnosis is to be achieved. We are also of the opinion that more weight should be given to the aforementioned nonconstant findings when faced by a thyroid aspirate with cell richness, syncytial clusters without acinar formation, and monolayered sheets. Diagn Cytopathol 1996;15:12–16. © 1996 Wiley-Liss, Inc.     

Fine-needle aspiration cytology of metastatic ovarian carcinoma to the breast

Metastatic ovarian carcinoma to the breast is rare. It represents a diagnostic challenge to the cytologist. It usually signifies a progressive widespread metastatic ovarian tumor with a poor prognosis. This report evaluates the breast fine-needle aspiration (FNA) cytomorphologic features of six cases of metastatic ovarian carcinoma and compares them to those reported in the literature. The cytologic features included hypercellularity, abundant papillary fragments, and necrotic background. The tumor cells showed high nuclear/cytoplasmic ratio, anisonucleosis, prominent nucleoli, and psammoma bodies in cases of serous papillary carcinoma. In addition, the clear-cell carcinoma had prominent finely vacuolated and clear cytoplasm, multinucleated giant cells, and papillary fragments with hobnail nuclei. Recognition of these unusual patterns in a breast FNA cytology should raise the suspicion of a metastatic ovarian tumor. Direct comparison between the breast FNA cytology and the original primary ovarian tumor should confirm the diagnosis. The proper diagnosis of metastatic ovarian cancer to the breast will prevent unnecessary surgical treatment and ensure the appropriate therapy. Diagn Cytopathol 1996;15:1–6. © 1996 Wiley-Liss, Inc.     

The oncocyte that went places: Diagnosis with EUS‐guided FNA

Although uncommon, Hurthle cell neoplasms have a characteristic histologic and cytologic features which often aid in the diagnosis of these lesions. In fine needle aspiration biopsies, determining malignant potential on cytologic features is challenging unless other evidence of malignancy (such as metastases) are known. The role of EUS‐guided FNA in diagnosing superior mediastinal masses has been described previously. It's role in evaluating subcarinal metastases from lung cancer primaries have also heen studied. However we describe metastatic thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS‐guided FNA combining the unique cytologic features o Hurthle cell neoplasms and the versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual neoplasm. Diagn. Cytopathol. 2013;41:977–979. © 2011 Wiley Periodicals, Inc.     

Rare thyroid tumors: spindle-cell epithelial tumor and thyroid carcinoma with thymus-like differentiation

The paper describes 2 cases of spindle-cell epithelial thyroid tumors (SETTLE) and carcinoma showing thymus-like differentiation (CASTLE). They are rare types of thyroid tumors and must be distinguished from medullary carcinoma, anaplastic carcinoma, synovial sarcoma and malignant teratoma. The presented cases show both common and unusual features as compared with the previously described tumors. CASTLE probably arises from ectopic thymus tissue. The further examination is needed to highlight the histogenesis of SETTLE, and to collect additional data on its aggressiveness and clinical outcome.     

Metastatic nasopharyngeal carcinoma initially presenting as cervical lymphadenopathy. A report of two cases that resembled Hodgkin's disease.

We describe two patients with nasopharyngeal carcinoma who initially presented with cervical lymphadenopathy. Lymph node biopsy specimens in each patient were initially diagnosed as Hodgkin's disease. In both cases, the neoplastic cells had large, vesicular nuclei with prominent eosinophilic nucleoli; some neoplastic cells were identified in lacunar spaces. In addition, numerous inflammatory cells were present, including eosinophils, lymphocytes, and plasma cells. At the time of referral, the correct diagnosis of metastatic carcinoma was made, and primary nasopharyngeal carcinomas were subsequently identified. The possibility of metastatic nasopharyngeal carcinoma should always be considered in adults with enlarged cervical lymph nodes that resemble Hodgkin's disease. The cytologic features of the malignant cells are the clue to the correct diagnosis. Immunophenotypic studies easily resolve this diagnostic dilemma if the possibility of metastatic nasopharyngeal carcinoma is considered.     

Paraganglioma‐like medullary thyroid carcinoma: A case report and literature review

Medullary thyroid carcinoma (MTC) accounts for 3%‐5% of all thyroid malignancies. Most MTC can be diagnosed by their typical cytologic and histologic morphology and immunohistochemical features. However, some rare variants of MTC may pose diagnostic difficulties on both cytology and histology. Paraganglioma‐like MTC (PLMTC) is a rare, but widely recognized variant of MTC. PLMTC is known to share morphological and architectural similarities with paraganglioma, hyalinizing trabecular tumor, and carcinomas of thyroid follicular cell origin, such as follicular carcinoma and follicular variant of papillary thyroid carcinoma. The combination of clinicopathologic features and a battery of immunohistochemical markers is essential for making a correct diagnosis. Herein, we report one case of PLMTC with both cytologic and histologic features and review the clinicopathologic features of previously reported cases.     

Fine-needle aspiration cytology of metastatic small cell carcinoma of the colon: A report of three cases

Small cell carcinoma of the large intestine is a rare, extremely aggressive malignancy often associated with an overlying adenoma. We report three cases of metastatic small cell carcinoma of the colon diagnosed by fine-needle aspiration (FNA) biopsy. Two of the patients were women (ages 33 and 46 yr old) and one was a man (69 yr old). FNA biopsy established the diagnosis of metastatic small cell carcinoma involving the liver (2 cases) and soft tissue of the scapular region (1 case). In one patient, the FNA diagnosis of hepatic metastases preceded identification of the primary site. Subsequently, the patient was found to have a small cell carcinoma subadjacent to a colonic villous adenoma, illustrating the importance of investigating villous lesions of the colon in patients with metastatic small cell carcinoma of unknown primary origin (especially in non-smokers). All three cases showed the characteristic cytologic features of small cell carcinoma. Ancillary studies performed on aspirated material confirmed the diagnosis of small cell carcinoma in one case. Immunocytochemical studies revealed punctate cytokeratin and diffuse neuron-specific enolase (NSE) positivity of the malignant cells. Ultrastructurally neurosecretory granules were evident. To the best of our knowledge, this is the first FNA cytologic report of metastatic small cell carcinoma of the large intestine. This FNA report also demonstrates when a small cell carcinoma is detected in a metastatic site in a patient lacking a lung primary, a likely primary site could be adjacent or beneath a polypoid lesion of the colon. Diagn Cytopathol 1996;15:54–59. © 1996 Wiley-Liss, Inc.     

Cytologic features of ductal carcinoma in situ

Fourteen cases of both palpable and non-palpable breast lesions reported as possible ductal carcinoma in situ (DCIS) on fine-needle biopsy (FNB) over a 12-mo period were retrieved from our files and compared to the subsequent histologic diagnosis. Although a definite cytologic pattern of highly cellular smears with high grade nuclei, dissociation, and background necrosis with microcalcifications emerged for comedo DCIS, it was not possible to differentiate these on cytologic grounds from high grade infiltrating carcinoma with necrosis unless mammographic findings were taken into account. Useful criteria for non-comedo low grade DCIS were high cellularity, low grade nuclei, and architectural features of papillary and three dimensional (3D) fragments, palisade arrangements, and monolayer sheets with punched out glandular lumina. We conclude that FNB has a definite role in the diagnosis of these lesions, with the limitation that invasive malignancy can never be excluded on cytologic criteria alone and clinico-radiological correlation is paramount. Diagn Cytopathol 1996;15:367–373. © 1996 Wiley-Liss, Inc.     

Adenosquamous carcinoma of the bile duct: Cytologic features of brush specimens from two cases

Cytologic brushing is a safe and specific procedure for diagnosing carcinoma of the distal bile duct and proximal pancreatic duct. The vast majority of these lesions are pure adenocarcinomas. Occasionally, however, other morphologic subtypes may be encountered. We report our experience with two adenosquamous carcinomas of the bile duct diagnosed by cytologic brushing. Both patients presented clinically with jaundice and were found to have mass lesions obstructing the bile duct. The brush specimens were cellular and contained a mixture of glandular and squamous elements. The glandular component was characterized by cohesive aggregates of cells with hyperchromatic, overlapping nuclei. The squamous component contained clusters and individual cells with hyperchromatic oval-to-spindled nuclei and orangeophilic cytoplasm. Focally, the squamous elements appeared to gradually merge into the glandular component, and there were clusters of hybrid cells which were difficult to classify as squamous or glandular. Although uncommon, these 2 cases demonstrate that the cytologic features of adenosquamous carcinoma can be appreciated on cytologic brushing specimens. Diagn Cytopathol 1996;15:322–324. © 1996 Wiley-Liss, Inc.     

Metastatic medullary thyroid carcinoma in liver diagnosis by aspiration cytology

A case of metastatic medullary thyroid carcinoma (MTC) to the liver of a patient with multiple endocrine neoplasia (MEN) Type IIb was suggested by percutaneous fine-needle aspiration cytology and confirmed by histology and immunohistochemistry. The cytologic presentation of this unusual thyroid cancer in liver has not been previously reported. We report such a case and discuss its differential diagnosis from other metastatic tumors of the liver. Diagn Cytopathol 1994; 11:277–280. © 1994 Wiley-Liss, Inc.     

“Cannonballs” and psammoma bodies: Unusual cytologic features of metastatic pulmonary small‐cell carcinoma in a pleural effusion

Large three‐dimensional cell aggregates and psammoma bodies are usually encountered in benign serous effusions (mesothelial hyperplasia and endosalpingiosis), mesotheliomas, and metastatic papillary carcinomas. We report a case of pulmonary small‐cell carcinoma occurring in an 88‐year‐old woman that initially presented with a malignant pleural effusion characterized cytologically by a predominance of large three‐dimensional neoplastic cell aggregates (“cannonballs”), associated with rare psammoma bodies. Although the crowded three‐dimensional tumor‐cell aggregates did not allow detailed cytologic examination, the diagnosis of metastatic small‐cell carcinoma could be established noting the characteristic chromatin features of the occasional single neoplastic cells and the characteristic “cell‐in‐cell” and “stack‐of‐coins” arrangements of rare small clusters of neoplastic cells. Immunoperoxidase stains showing positivity of the tumor cells for CD56, synaptophysin, and TTF1 further supported this diagnosis. Endobronchial ultrasound‐guided fine‐needle aspiration of a mediastinal lymph node subsequently confirmed the diagnosis of pulmonary small‐cell carcinoma. Metastatic pulmonary small‐cell carcinoma should be considered in the differential diagnosis of serous effusions showing large three‐dimensional neoplastic cell aggregates and psammoma bodies to prevent a potential diagnostic pitfall. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.