C cell carcinoma of the thyroid--papillary type.

Two cases of papillary type of C cell carcinoma of the thyroid were reported. They showed papillary arrangement with fibrovascular stalk in properly fixed tissues. Histochemically argyrophil reaction was positive in the cytoplasm and amyloid deposited in the stroma. Ultrastructurally secretory granules were found in their cytoplasm. The papillary type is not an artifact but one of the histologic variations of this carcinoma.     

Renal-cell carcinomas in end-stage kidneys: a clinicopathological study with emphasis on clear-cell papillary renal-cell carcinoma and acquired cystic kidney disease-associated carcinoma

Clear-cell papillary renal-cell carcinoma (CCPC) and acquired cystic kidney disease-associated carcinoma (ACDAC) are neoplasms with distinct morphological characteristics that behave less aggressively than conventional renal-cell carcinomas. End-stage kidney specimens from 61 patients (47 males and 14 females) with 109 renal-cell carcinomas were selected. Papillary renal-cell carcinoma was the most common malignancy (61/109, 56%), followed by CCPC (20/109, 18%). The CCPC showed a papillary or tubular/solid architecture, clear cytoplasm, low nuclear grade, and a distinct immunohistochemical profile (RCC-, vimentin+, CK7+, p504S-). ACDAC displayed a variety of architectural patterns, eosinophilic cytoplasm, high nuclear grade, intratumoral calcium oxalate deposits, and an immunohistochemical profile similar to type 2 papillary renal-cell carcinoma (RCC+, vimentin+, CK7-/+, p504S+). Less than 5% (3/69) of pathologically staged renal-cell carcinomas in end-stage kidneys presented with lymphogenous and/or hematogenous metastases.     

Papillary renal cell‐like carcinoma in a retroperitoneal teratoma

We report a case of somatic type malignancy with papillary renal cell carcinoma differentiation arising in a retroperitoneal mixed germ cell tumor. The patient was a 36‐year‐old man with a synchronous mediastinal teratoma. The somatic type malignancy in the retroperitoneal tumor was composed of papillary structures covered by atypical epithelial cells with eosinophilic cytoplasm, prominent nucleoli and pseudostratified nuclei. Papillary cores contained numerous aggregates of foamy macrophages, typical of type I papillary renal cell carcinomas. The immunohistochemical profile was consistent with papillary renal cell carcinoma, including positive reactions for cytokeratin 7 and alpha‐methyl acyl CoA racemase. There was no somatic type malignancy component in the synchronous mediastinal teratoma. Both the retroperitoneal and the mediastinal tumor showed gains of 12p and chromosome 17 material. There was no c‐MET mutation in the somatic type malignancy. To our knowledge, this is the first report of a somatic type malignancy with features of papillary renal cell carcinoma arising in a germ cell tumor. It is important not to confuse such a retroperitoneal tumor with a conventional papillary renal cell carcinoma, because presence of other malignant histologies within the germ cell tumor may warrant different treatment. In such cases, the presence of isochromosome 12p can be helpful to the diagnosis.     

An immunohistochemical study of cytokeratin and vimentin in benign and malignant thyroid lesions

Intermediate filaments in benign and malignant thyroid lesions were immunohistochemically studied using polyclonal and monoclonal anti-cytokeratin (CK), and monoclonal anti-vimentin antibodies. Antigenicity of CK and vimentin was almost completely destroyed during formalin fixation in normal thyroid and all thyroid lesions except for some cases of papillary and squamous cell carcinoma, although the latter showed negative immunostaining with anti-vimentin antibody. In sections fixed with Carnoy's fixative, most cases of papillary carcinoma showed an intense reaction product for polyclonal anti-CK, monoclonal anti-CK-7, CK-19 and anti-vimentin antibodies. The reaction product for anti-CK antibodies was located mainly in the apical cytoplasm and that for anti-vimentin antibody in the basal cytoplasm. However antigenicity was still destroyed by the fixative in many specimens of normal thyroid, benign thyroid lesions and follicular carcinoma. In frozen sections, all specimens showed preserved antigenicity for both antigens with an intense reaction product in papillary carcinoma, but this was weaker in normal thyroid, benign thyroid lesions and follicular carcinoma. Therefore, follicular cells under normal and pathological conditions contain intermediate filaments of CK and vimentin in their cytoplasm and co-expression of the antigens is significantly increased in papillary carcinoma.     

An Immunohistochemical Study of Cytokeratin and Vimentin in Benign and Malignant Thyroid Lesions

Intermediate filaments in benign and malignant thyroid lesions were immunohistochemically studied using polyclonal and monoclonal anti-cytokeratin (CK), and monoclonal anti-vimentin antibodies. Antigenicity of CK and vimentin was almost completely destroyed during formalin fixation in normal thyroid and all thyroid lesions except for some cases of papillary and squamous cell carcinoma, although the latter showed negative immunostaining with anti-vimentin antibody. In sections fixed with Carnoy's fixative, most cases of papillary carcinoma showed an intense reaction product for polyclonal anti-CK, monoclonal anti-CK-7, CK-19 and anti-vimentin antibodies. The reaction product for anti-CK antibodies was located mainly in the apical cytoplasm and that for anti-vimentin antibody in the basal cytoplasm. However antigenicity was still destroyed by the fixative in many specimens of normal thyroid, benign thyroid lesions and follicular carcinoma. In frozen sections, all specimens showed preserved antigenicity for both antigens with an intense reaction product in papillary carcinoma, but this was weaker in normal thyroid, benign thyroid lesions and follicular carcinoma. Therefore, follicular cells under normal and pathological conditions contain intermediate filaments of CK and vimentin in their cytoplasm and co-expression of the antigens is significantly increased in papillary carcinoma.     

Morphologic typing of papillary renal cell carcinoma: comparison of growth kinetics and patient survival in 66 cases.

Whereas papillary renal cell carcinoma is now established as a subtype of renal cell neoplasia, division of these tumors into 2 distinctive morphotypes has been proposed. Type 1 tumors have cells with scanty pale cytoplasm arranged in a single layer on the basement membrane of papillary cores. In these tumors, psammoma bodies and foamy macrophages are frequently seen, and the tumors frequently express cytokeratin 7. Type 2 tumor cells have pseudostratified nuclei and usually have voluminous eosinophilic cytoplasm. Recent studies have supported this subclassification of papillary renal cell carcinoma by demonstrating differing genotypes for type 1 and 2 tumors. To further study the subclassification of papillary renal carcinoma, we compared clinical features, nuclear grade, stage, tumor growth kinetics, and survival in a series of 50 type 1 and 16 type 2 papillary renal cell carcinomas. Comparison of patient age at presentation, sex, and primary tumor size shows no significant difference between the 2 tumor types. Type 1 tumors were of significantly lower Fuhrman grade (P =.0001) and higher Robson stage (P =.009) than type 2 tumors. There was no significant difference when tumors were staged according to the TNM classification. Assessment of tumor growth kinetics showed significantly different mean silver-staining nucleolar organizer region (AgNOR) scores and Ki-67 indices (AgNOR type 1, 3.83, type 2, 7.24, P =.0001; Ki-67 type 1, 3.17%, type 2, 6.01%, P =.0002). Multivariate analysis showed tumor type (P =.03), presence of metastases (P =.04), AgNOR score (P =.001), and Ki-67 index (P =.03) to be independently associated with survival. These results provide evidence of the clinical utility of dividing papillary renal cell carcinomas into 2 types according to histologic characteristics.     

Chromosomal Imbalances in Papillary Renal Cell Carcinoma : Genetic Differences between Histological Subtypes

Papillary renal-cell carcinoma (RCC) is a renal carcinoma variant with distinct gross, microscopic, and cytogenetic features. Recently, a type 1 (pale cytoplasm, small-cell) and a type 2 (eosinophilic cytoplasm, large-cell) subtype of papillary RCC have been described. Chromosomal alterations associated with these tumor types were examined in 25 papillary RCCs by comparative genomic hybridization. Relative copy number gains were frequently detected at chromosomes 7p (56%), 7q (44%), 12q (28%), 16q (32%), 17p (56%), 17q (76%), and 20q (32%). Chromosomal regions that were most often lost included 1p (24%), 4q (36%), 6q (40%), 9p (36%), 13q (36%), Xp (28%), Xq (36%), and Y (73%). There were clinical and genetic differences between the subtypes of papillary RCC. Type 2 tumors were of higher nuclear grade (P = 0.0012) and higher stage (P = 0.01) and had a worse prognosis (P = 0.03) than type 1 tumors. The number of DNA gains per tumor, especially gains of 7p and 17p, was significantly higher in type 1 than in type 2 tumors (P < 0.01). These data suggest the existence of two distinct morphological and genetic subgroups of papillary RCC. Losses of chromosome Xp were associated with short patient survival (P < 0.01). Despite the small number of cases, this finding suggests that a gene on chromosome Xp may contribute to papillary RCC progression.     

Fine‐needle aspiration findings of Xp11 translocation renal cell carcinoma metastatic to a hilar lymph node

Xp11 translocation renal cell carcinoma (RCC) is a specific type of renal cell carcinoma recently placed under the “MiT family translocation RCC” at the last 2013 ISUP Vancouver classification of renal neoplasia. This tumor contains variable proportions of clear cells and could easily mimic papillary RCC, clear cell type, and clear cell papillary RCC. Given the small number of published cytologic findings of this tumor, it could easily present as a diagnostic pitfall. We describe a case of a 23‐year‐old man with a history of prior nephrectomy who presented with multiple mediastinal lymphadenopathies on imaging surveillance follow‐up. Fine‐needle aspiration of the lymph node showed tumor cells with voluminous clear to eosinophilic cytoplasm, well‐defined cell borders and hyperchromatic nuclei arranged in papillary architecture. Review of the prior nephrectomy specimen showed papillary cores surrounded by cells with voluminous clear to finely granular eosinophilic cytoplasm and distinct cell borders. Immunohistochemical stains performed on the nephrectomy specimen showed tumor positivity for CD10, E‐cadherin, a‐methylacyl coenzyme A racemase, and TFE3 supporting the diagnosis of Xp11 translocation renal cell carcinoma. Although this tumor was initially described predominantly in children, it could also occur in adults, as seen in this case. Familiarity with the cytologic findings of this tumor, use of immunohistochemical stains, or cytogenetic test to determine the type of gene fusion will be extremely useful in arriving at the correct diagnosis. Diagn. Cytopathol. 2017;45:456–462. © 2017 Wiley Periodicals, Inc.     

Dilated rough endoplasmic reticulum corresponding to septate cytoplasmic vacuoles in papillary thyroid carcinoma

Septate cytoplasmic vacuoles, which are one of the cytologic findings characteristic of papillary thyroid carcinoma, are small, uniform, and well-defined vacuoles, with defined strands of cytoplasm separating them. We report on a case with histologic and ultrastructural findings corresponding to septate cytoplasmic vacuoles, which have not been previously described. The patient was a 51-yr-old man with a mass in the left anterior of the neck, measuring 4.0 x 3.5 cm in diameter. Aspiration cytology smears revealed findings typical of papillary thyroid carcinoma, including papillary tissue fragments, intranuclear inclusions, nuclear grooves, powdery chromatin, and psammoma bodies. The tumor cells which were located at the periphery of small three-dimensional clusters, and others which showed a sheet-like arrangement, demonstrated uniform, small vacuoles in relatively abundant, dense cytoplasm. Histologically, a small number of papillary thyroid carcinoma cells with multiple vacuoles were observed, which were limited to the hobnail-shaped cells located at papillary configurations or floating tumor cells within the papillary lumen. Ultrastructurally, the hobnail-shaped tumor cells demonstrated various-sized dilated rough endoplasmic reticulum and rich heterochromatin. We emphasize that septate cytoplasmic vacuoles correspond to dilated rough endoplasmic vacuoles and are probably related to degenerative changes.     

Ultrastructural observations on the capillaries of human thyroid tumours.

Ultrastructure of the capillaries of malignant and benign thyroid tumours has been examined. The material consisted of biopsies from six cases of thyroid papillary carcinoma, one case of follicular (foetal type) adenoma and six cases of nodular adenomatous goitre. In the group of nodular adenomatous goitre and in the follicular adenoma, the capillary wall was made up of fenestrated endothelium similar to that of capillaries of normal human thyroid. The fenestrae occupied a large area of the endothelial wall. Micro- and macropinocytotic vesicles were frequent in the endothelial cytoplasm. In the thyroid carcinomas the papillary structures always contained numerous capillaries with fenestrated endothelium. The microfollicular area and the solid tumoral areas of the papillary carcinoma showed occasional capillaries with fenestrated endothelium, but many capillaries were lined with continuous endothelium. The capillaries in all the specimens were surrounded externally by a continuous basement membrane which was frequently bilaminate or multilaminate. This study indicates that capillaries with fenestrated endothelium are characteristic of thyroid tumours which arise from follicular cells.     

Hereditary and Sporadic Papillary Renal Carcinomas with c-met Mutations Share a Distinct Morphological Phenotype

Germline mutations of c-met oncogene at 7q31 have been detected in patients with hereditary papillary renal cell carcinoma. In addition, c-met mutations were shown to play a role in 13% of patients with papillary renal cell carcinoma and no family history of renal tumors. The histopathology of papillary renal cell carcinoma with c-met mutations has not been previously described. We analyzed the histopathology of 103 bilateral archival papillary renal cell carcinomas and 4 metastases in 29 patients from 6 hereditary papillary renal cell carcinoma families with germline c-met mutations and 6 papillary renal cell carcinomas with c-met mutations from 5 patients with no family history of renal tumors. Twenty-five sporadic renal tumors with prominent papillary architecture and without somatic c-met mutations were evaluated for comparison. All papillary renal cell carcinomas with c-met mutations were 75 to 100% papillary/tubulopapillary in architecture and showed chromophil basophilic, papillary renal cell carcinoma type 1 histology. Fuhrman nuclear grade 1-2 was seen in tumors from 23 patients, and nuclear grade 3 was observed focally in 8 patients. Seventeen patients had multiple papillary adenomas and microscopic papillary lesions in the surrounding renal parenchyma. Clear cells with intracytoplasmic lipid and glycogen were focally present in tumors of 94% papillary renal cell carcinoma patients. Clear cells of papillary renal cell carcinoma had small basophilic nuclei, and clear cell areas lacked a fine vascular network characteristic of conventional (clear) cell renal cell carcinoma. We conclude that papillary renal cell carcinoma patients with c-met mutations develop multiple, bilateral, papillary macroscopic and microscopic renal lesions. Renal tumors with c-met genotype show a distinctive papillary renal cell carcinoma type 1 phenotype and are genetically and histologically different from renal tumors seen in other hereditary renal syndromes and most sporadic renal tumors with papillary architecture. Although all hereditary and sporadic papillary renal cell carcinomas with c-met mutations share papillary renal cell carcinoma type 1 histology, not all type 1 sporadic papillary renal cell carcinomas harbor c-met mutations.     

Warthin-like papillary carcinoma of the thyroid

BACKGROUND: Warthin-like papillary carcinoma of thyroid is characterized by distinct papillary formations lined by tumor cells with oncocytic cytoplasm, nuclear features of papillary carcinoma, and brisk lymphoplasmacytic infiltrates in the papillary stalks. This tumor derives its name from its close resemblance to Warthin tumor of major salivary glands. DESIGN: The clinicopathologic features of 17 patients with Warthin-like papillary carcinoma were studied. RESULTS: Fifteen tumors occurred in women and 2 arose in men (age range, 23-63 years). The lesions ranged in size from 3 mm to 2.5 cm. Fine-needle aspiration biopsies were performed in 7 cases; 4 were diagnosed as papillary carcinoma, 2 as consistent with lymphocytic thyroiditis, and 1 as atypical cells. All 17 tumors were confined to the thyroid; 6 showed prominent cyst formation and the remaining tumors were solid. In each case, the tumor arose in a background of lymphocytic thyroiditis. Nodal metastases were identified in 3 cases; however, none showed distant metastases. In 7 cases, foci of papillary microcarcinoma and follicular variant of papillary carcinoma were found in other areas of the thyroid. CONCLUSIONS: Warthin-like tumors can be mistaken for benign lymphoepithelial lesions of the thyroid, Hürthle cell carcinoma, and tall cell variant of papillary carcinoma in both fine-needle aspiration and histology specimens. Follow-up information on the previously reported cases has suggested that these tumors behave similarly to usual papillary carcinoma. The extensive lymphocytic infiltration in these tumors and their association with chronic lymphocytic thyroiditis may suggest a role for immunological mechanisms in the pathogenesis of thyroid tumors.     

Fine-Needle Aspiration Cytology of Papillary Hurthle Cell Carcinoma with Lymphocytic Stroma "Warthin-Like Tumor" of the Thyroid

Papillary Hurthle cell carcinoma with lymphocytic stroma is a recent addition to the list of variants of papillary carcinoma of the thyroid. We report the aspiration cytology and histology findings of this tumor arising in two patients. The smears were cellular, and revealed Hurthle cells arranged in three-dimensional groups, papillary fragments, and as singly dispersed cells with a prominent intimately associated inflammatory component of lymphocytes and few plasma cells. The Hurthle cells were pleomorphic and showed granular eosinophilic cytoplasm, eccentrically oriented nuclei with prominent nucleoli. Nuclear features of papillary carcinoma were present among both the cellular groups and scattered cells. The histologic examination showed a circumscribed papillary tumor comprising Hurthle cells and a brisk inflammatory component filling the stalks of papillae, These findings were consistent with a papillary Hurthle cells carcinoma with lymphocytic stroma, the so-called Warthin-like tumor of the thyroid. Hurthle cells admixed with inflammatory cells in cytology preparations can be seen in Hurthle cell nodules or neoplasms arising in a background of chronic lymphocytic thyroiditis. We suggest that a careful search for nuclear features may be helpful in diagnosing this variant of papillary carcinoma.     

乳腺富糖原透明细胞癌2例报道及文献复习

目的 探讨乳腺富糖原透明细胞癌临床病理特点及鉴别诊断要点。方法 对2例乳腺富糖原透明细胞癌进行临床资料及光镜和免疫组化标记观察。结果 组织学特点：癌细胞为多边形或柱状，胞界清楚，胞质透明，呈实性巢状、片状排列，可有乳头形成。表现为导管内癌和浸润性癌结构。免疫组化染色显示：癌细胞呈上皮性免疫表型，CK(AE1)、CEA强阳性，不表达S-100蛋白、肌动蛋白。PAS染色阳性。结论 富含糖原透明细胞癌是上皮性特殊类型乳腺癌，其诊断主要依靠组织病理学和免疫组化标记。     

Intraductal oncocytic papillary carcinoma of the pancreas showing numerous hyaline globules in the lumen

Two cases of intraductal oncocytic papillary carcinoma (IOPC) treated surgically were analyzed on light microscopy and immunohistochemistry: that of a 61-year-old man and that of a 55-year-old man. There were no clinical symptoms in either case. Pancreatic abnormalities were discovered incidentally on CT. Various clinical examinations were carried out, and the preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC) in both cases. Surgery was performed. Macroscopic observation of tissue cross-sections indicated multilocular cystic mass containing polypoid lesions encapsulated by the dilated pancreatic duct. Histologically, the cyst walls were lined by columnar epithelial cells with complex papillary projections associated with oxyphilic cytoplasm, and they were strongly immunoreactive with anti-mitochondrial antibody in the cytoplasm. Electron microscopy showed numerous mitochondria in the cytoplasm. IOPC was diagnosed. Interestingly, amorphous hyaline globules were produced from the oxyphilic cells, which exhibited a bud-like appearance. The hyaline globules were not positive for mucin staining. No case of IPMC with hyaline globules has been reported to date. The production of hyaline globules may be related to oncocytic differentiation. It is suggested that hyaline globules should be regarded as a characteristic of IOPC.     

Immunohistochemical study of lung adenocarcinoma using monoclonal antibody for 60-kilodalton antigen in type II pneumocytes and nonciliated bronchiolar epithelial cells. Comparison with two antisurfactant apoprotein antibodies

Monoclonal antibody KP16D3 was produced by immunizing mice with monkey bronchoalveolar lavage. KP16D3 revealed the immunohistochemical reactivity in the cytoplasm of some nonciliated bronchiolar epithelial cells and type II pneumocytes and thereby recognized specifically a protein with an apparent molecular weight of 60 kD with the use of Western blotting and immunoaffinity column chromatography followed by SDS-PAGE. Examination of 76 primary and 4 metastatic lung carcinomas in primary lung carcinoma KP16D3 showed immunohistochemical positivity only to mucin-nonproducing papillary adenocarcinoma (27/28) and bronchioloalveolar carcinoma (2/2), except for one case of large cell carcinoma. All other primary lung carcinomas such as squamous cell carcinoma, acinar adenocarcinoma, and small cell carcinoma had negative results. From these findings, KP16D3 seems to be an effective immunohistochemical marker of mucin-nonproducing papillary adenocarcinoma and bronchioloalveolar carcinoma of the lung and it appears to be useful to investigate both the histogenesis and functional expression of primary lung adenocarcinoma.     

Fine-needle aspiration cytology of papillary Hürthle cell carcinoma with lymphocytic stroma “Warthin-like tumor” of the thyroid

Papillary Hürthle cell carcinoma with lymphocytic stroma is a recent addition to the list of variants of papillary carcinoma of the thyroid. We report the aspiration cytology and histology findings of this tumor arising in two patients. The smears were cellular, and revealed Hürthle cells arranged in three-dimensional groups, papillary fragments, and as singly dispersed cells with a prominent intimately associated inflammatory component of lymphocytes and few plasma cells. The Hürthle cells were pleomorphic and showed granular eosinophilic cytoplasm, eccentrically oriented nuclei with prominent nucleoli. Nuclear features of papillary carcinoma were present among both the cellular groups and scattered cells. The histologic examination showed a circumscribed papillary tumor comprising Hürthle cells and a brisk inflammatory component filling the stalks of papillae. These findings were consistent with a papillary Hürthle cells carcinoma with lymphocytic stroma, the so-called Warthin-like tumor of the thyroid. Hürthle cells admixed with inflammatory cells in cytology preparations can be seen in Hürthle cell nodules or neoplasms arising in a background of chronic lymphocytic thyroiditis. We suggest that a careful search for nuclear features may be helpful in diagnosing this variant of papillary carcinoma.     

Identification of basic fibroblast growth factor in papillary carcinoma of the thyroid

Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin-Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.