The best immunohistochemical panel for differentiating hepatocellular carcinoma from metastatic adenocarcinoma

It can be difficult to differentiate hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA). An appropriate immunohistochemical panel is required for the differential diagnosis. This study aimed at finding the best panel, including hepatocyte-specific antigen (Hepatocyte), pCEA, CD10, Villin, CD34, TTF-1, MOC-31, CK7, and CK20 antibodies. Sixty-eight cases of HCC and 107 cases of MA were investigated. Hepatocyte positivity was seen in 95.6% of HCCs and in 1.9% of MAs. pCEA was expressed in 47.8% of HCCs and in 86.8% of MAs. CD10 stained 73.13% of HCCs and 36.9% of MAs. Villin was positive in 23.5% of HCCs and in 81.0% of MAs. Canalicular staining with pCEA, CD10, and Villin was seen only in HCCs. Sinusoidal CD34 staining was seen only in 42.6% of HCCs. A small subset of HCCs demonstrated cytoplasmic TTF-1 and MOC-31. CK7 was expressed in 29.4% of HCCs and in 29.9% of MAs, whereas CK20 stained 14.7% of HCCs and 62.6% of MAs. In conclusion, Hepatocyte should be combined with pCEA, MOC-31, CD10, and CD34. Canalicular staining with pCEA, CD10, and Villin is specific for HCC. CK7 and CK20 expression may be seen in some HCCs. We suggest that the best panel for discriminating HCC from MA should contain Hepatocyte, MOC-31, pCEA, CD10, and CD34.     

Mixed ovarian large cell neuroendocrine carcinoma, mucinous adenocarcinoma, and teratoma: A report of two cases and review of the literature

Large cell neuroendocrine carcinoma of the ovary is a rare recently established entity. Few cases have been reported in the literature, and they are usually associated with another type of surface epithelial tumor. The association of a large cell neuroendocrine carcinoma with a surface epithelial tumor and a teratoma is even rarer, with only two cases previously described. We report the cases of two patients in their fifties who presented with a growing abdominal mass and died of metastatic disease within less than a year. Histological assessment revealed large cell neuroendocrine carcinoma admixed with mucinous adenocarcinoma and teratoma. Different hypotheses regarding the origin of large cell neuroendocrine carcinoma of the ovary are discussed. The immunohistochemical pattern of staining for cytokeratin 7 and cytokeratin 20 suggests that the composite epithelial tumors originated from the pre-existing teratoma.     

涎腺腺样囊性癌的免疫组织化学及免疫电镜观察

采用抗平滑肌的肌动蛋白（ａｃｔｉｎ）、肌球蛋白（ｍｙｏｓｉｎ）、Ｓ—１００蛋白和胶质纤维酸性蛋白（ＧＦＡＰ）对４例涎腺腺样囊性癌进行免疫组化和免疫电镜研究。结果发现，该癌中肿瘤性肌上皮细胞对抗ａｃｔｉｎ、ｍｙｏｓｉｎ和Ｓ—１００蛋白反应阳性，对抗ＧＦＡＰ反应阴性。这些细胞衬里在囊样腔隙周边、小导管外周或散在于上皮团块中；肿瘤性腺上皮细胞对上述抗体反应阴性。讨论了肿瘤性肌上皮细胞的分化趋向和免疫特性。     

A case of primary ductal adenocarcinoma of the lacrimal gland: histopathological and immunohistochemical study

We encountered primary ductal adenocarcinoma of the lacrimal gland in a 67-year-old Japanese man. To the best of our knowledge, only three cases of primary ductal adenocarcinoma of the lacrimal gland have been reported in the literature. The patient was admitted because of visual disturbance, and a mass measuring about 3 cm in diameter was revealed in the right orbit. The mass was resected, and primary ductal adenocarcinoma of the lacrimal gland was diagnosed histopathologically. He died from recurrence at the primary site and metastasis to the brain, lungs, liver, common bile duct, and pancreas 2 years and 10 months after surgery although adjunctive orbital radiotherapy was given. Immunohistochemically, the characteristics of cancer cells were similar to those of salivary duct carcinoma, namely positivity for cytokeratin (CK) 7, 10, 17, 18, 19, and 34betaE12, and negativity for CK20. It was not clear whether the ductal adenocarcinoma originated from the ductal or acinar epithelium of the lacrimal gland, because the immunohistochemical features of both epithelia were identical.     

Urachal adenocarcinoma metastatic to the ovaries resembling primary ovarian mucinous carcinoma: a case report with the immunohistochemical study

Urachal adencarcinoma is rare and its metastasis to the ovary is extremely rare. I report here on a case of urachal adenocarcinoma that metastasized to bilateral ovaries in a 72-year-old female. She presented with vaginal spotting. Abdominal CT revealed a huge multiloculated cystic mass in the recto-uterine pouch and a solid mass with dot calcification in the anterior pelvic cavity. The resected ovaries were equal-sized at about 10cm at the greatest diameter. The sectioned surfaces were predominantly multicystic with a solid nodule. Microscopically, both ovaries were mainly composed of cystic glands lined by mucin-containing epithelium with atypical nuclei. The solid nodule consisted of irregularly infiltrating glands and single tumor cells. Two years later, the patient was admitted with hema-turia. The kidney CT revealed a solid mass with calcification in the bladder dome, which suggested urachal carcinoma. The partial cystectomy specimen revealed an ill-defined ulcerative tumor. Histologically, the tumor corresponded to mucinous adenocarcinoma and centered at the bladder wall with predominant invasion of the muscularis. The immunohistochemical profiles of the ovarian and urachal tumors were exactly the same. The tumor cells were diffusely positive for CK20, CDX-2, MUC2 and MUC5AC, focally positive for 34(3E12 and negative for CK7.     

Urachal adenocarcinoma metastatic to the ovaries resembling primary ovarian mucinous carcinoma: a case report with the immunohistochemical study

Urachal adencarcinoma is rare and its metastasis to the ovary is extremely rare. I report here on a case of urachal adenocarcinoma that metastasized to bilateral ovaries in a 72-year-old female. She presented with vaginal spotting. Abdominal CT revealed a huge multiloculated cystic mass in the recto-uterine pouch and a solid mass with dot calcification in the anterior pelvic cavity. The resected ovaries were equal-sized at about 10cm at the greatest diameter. The sectioned surfaces were predominantly multicystic with a solid nodule. Microscopically, both ovaries were mainly composed of cystic glands lined by mucin-containing epithelium with atypical nuclei. The solid nodule consisted of irregularly infiltrating glands and single tumor cells. Two years later, the patient was admitted with hema-turia. The kidney CT revealed a solid mass with calcification in the bladder dome, which suggested urachal carcinoma. The partial cystectomy specimen revealed an ill-defined ulcerative tumor. Histologically, the tumor corresponded to mucinous adenocarcinoma and centered at the bladder wall with predominant invasion of the muscularis. The immunohistochemical profiles of the ovarian and urachal tumors were exactly the same. The tumor cells were diffusely positive for CK20, CDX-2, MUC2 and MUC5AC, focally positive for 34(3E12 and negative for CK7.     

Micropapillary carcinoma of the parotid gland arising in mucinous cystadenoma

We describe a 45-year-old man who had a 2-year history of a slowly enlarging tumor in the left parotid gland. Histologically, the tumor was a mucinous cystadenoma with focal apocrine differentiation, which revealed a widespread invasive micropapillary adenocarcinoma component. A rim of lymphoid tissue surrounded the margins of the micropapillary carcinoma. The invasive micropapillary adenocarcinoma component was morphologically identical with the invasive micropapillary carcinoma of the mammary gland. The tumor is different from so-far recognized salivary gland tumor entities. Received: 25 October 1999 / Accepted: 13 June 2000     

Renal mucinous tubular and spindle cell carcinoma: report of four cases and literature review

Mucinous tubular and spindle cell carcinoma of the kidney (MTSCC-K) is an unusual renal tumor. It is important to increase the recognition of the clinicopathological features of MTSCC-K and improve its clinical and differential diagnosis. This report described four cases of MTSCC-K with clinical, imaging, and pathological examination and showed that the tumor boundaries of MTSCC-K were clear, and tumor cells arranged into tubules and cord-like beams, between which was lightly stained myxoid stroma. The tumor cells were smaller and cube- or oval-shaped, with single small eosinophilic nucleoli, low-grade nuclei, and little nuclear fission. The myxoid stroma was scattered around lymphocytes and plasma cells. Immunohistochemical markers including CK7, CD117, EMA (epithelial membrane antigen), vimentin, and CK8/18, showed positive expression in tumor cells, but the tumor cells were negative for CD10 and villin. The proliferation index of Ki-67 was 5-10%. Since MTSCC-K is a rare low-grade malignancy, with unique histological and immunohistochemical characteristics, it is important for clinicians and pathologists to have a defined awareness of this tumor type in order to decrease the rate of misdiagnosis.     

Fluorine and thyroid gland function: A review of the literature

Summary The increasing use of fluoride for prevention of dental caries poses the problem as to whether this halogen has antagonistic properties towards iodine, whereby it could hamper the success of iodine prophylaxis of endemic goitre. Review of the literature shows that some authors have found an inhibition by fluoride of various steps of thyroid hormone biosynthesis in animal experiments. By and large, the inhibition was only slight and it was elicited only with fluoride doses greatly in excess of those recommended for caries prevention. The inhibition was not consistently present and other authors could not confirm it in comparable experiments. There is no convincing evidence that fluoride produces true goitres with epithelial hyperplasia in experimental animals. There are some reports based on casual observations that fluoride is goitrogenic in man. On the other hand, several good studies with adequate exposed and control populations failed to detect any goitrogenic effect of fluoride in man. It is noteworthy in particular that fluoride does not potentiate the consequences of iodine deficiency in populations with a borderline or low iodine intake. Published data fail to support the view that fluoride, in doses recommended for caries prevention, adversely affects the thyroid.     

涎腺腺泡细胞癌临床病理分析并文献复习

目的：探讨涎腺腺泡细胞癌的临床病理学特点及诊断要点。方法：对1例涎腺腺泡细胞癌进行临床资料、病理形态学及免疫组织化学观察,并结合文献对其诊断及鉴别诊断进行探讨。结果：镜下瘤细胞胞体宽大,胞浆嗜碱性呈细颗粒状,核圆形瘤细胞生长呈腺泡状或实性片状生长,部分区域呈乳头状改变,免疫组化显示AE1/AE3(+)、CK8/18(+)、CK7(+)、AAT(+)、S-100(+)。结论：涎腺腺泡细胞癌发病率低,但根据其常见的发病部位及特征性的组织形态,结合免疫组织化学方法,有助于其诊断及鉴别诊断。     

Cytology diagnosis of metastatic clear cell renal cell carcinoma,synchronous to pancreas,and metachronous to thyroid and contralateral adrenal: Report of a case and literature review

Renal cell carcinoma metastases to pancreas, thyroid, and contralateral adrenal gland are decidedly uncommon. Clear cell renal cell carcinoma (CCRCC) is the most frequent subtype. Cytology diagnosis may be challenging. A 74‐year‐old male with remote history of vocal cord malignancy and hypertension presented with abdominal pain. Computed tomography (CT) revealed 8.4 cm left renal mass highly suspicious for renal cell carcinoma, a 1.8 cm mass within vessels near left adrenal and a 2.5 cm mass in pancreatic tail. Right pulmonary middle lobe showed two small nodules. Metastatic CCRCC was diagnosed on preoperative transgastric, endoscopic ultrasound guided fine‐needle aspiration cytology of pancreatic tail mass. Left radical nephrectomy and distal pancreatectomy and splenectomy confirmed CCRCC (pT3bNxM1), with metastases in adrenal and pancreatic tail. The 3p deletion identification in pancreatic tumor suggested CCRCC origin. Follow‐up positron emission tomography‐CT (PET‐CT) scan revealed left thyroid lower pole mass. Thyroid ultrasound showed three clustered 6 mm nodules in left mid pole. Ultrasound‐guided fine needle aspiration (US‐FNA) biopsies, 4‐month post‐nephrectomy, were consistent with metastatic renal cell carcinoma in lower, and atypia of undetermined significance in mid poles respectively. Left lobectomy and isthmus and pyramidal lobe resections confirmed metastatic renal cell carcinoma. One year post‐radical nephrectomy, contralateral adrenal lesion noted on PET‐CT was interpreted as metastatic CCRCC on CT‐guided core biopsy with touch imprints. Rapid on‐site evaluation was implemented, and immunoprofile typical of CCRCC substantiated cytomorphology at all three sites. Previously reported cases of renal cell carcinoma metastases to organs as in the described case are reviewed as well. Diagn. Cytopathol. 2017;45:161–167. © 2016 Wiley Periodicals, Inc.     

Plasma cell granuloma of the thyroid gland mimicking carcinoma: a case report and review of the literature

Plasma cell granulomas (PCG) are rare tumor-like lesions consisting of sheets of polyclonal plasma cells admixed with numerous lymphocytes and other inflammatory cells surrounded by fibrous stroma. They usually appear in the lung, but involvement of diverse extrapulmonal sites has been described. PCGs occurring in the thyroid are very uncommon. Since 1981, only 11 cases have been described in the English literature. Here, we present the case of a 50-year-old Arabic man who noticed an enlargement of his thyroid gland during the previous 2 years, and he developed swallowing disturbances and a feeling of narrowness in the neck. A nearly total resection of the thyroid gland was made because of clinical suspicion of carcinoma. On histologic examination, PCG of the thyroid associated with Hashimoto's thyroiditis (HT) was diagnosed. This is the first case in which molecular pathological analyses for EBV and HHV8 DNA were made. As these were negative, distinct etiological features were suggested.     

Mucinous tubular and spindle cell carcinoma: a report of 15 cases and a review of the literature

Mucinous tubular and spindle cell carcinomas are low-grade renal epithelial neoplasms, which were first recognized as a specific entity in the World Health Organization 2004 classification. Forty-five documented cases have been reported. We present 15 additional cases that were incidentally discovered in ten women and five men, with a mean age of 53 years. The tumor is characteristically made up of large eosinophilic regular spindle cells separated by a myxoid stroma with intercellular alcian-blue-positive clear droplets. In peripheral areas, elongated tubules and papillae covered by cubic cells are found. Until this entity had been defined, pathologists used to classify these tumors as variants of solid papillary carcinomas with compressed and elongated papillae, metanephric adenomas, and sarcomatoid carcinomas. In the literature, cytogenetic data indicate various chromosomal losses and gains, but no loss of 3p or trisomy 7 and/or trisomy 17. In two cases, we demonstrate chromosomal loss involving chromosomes 1, 4, 6, 11, 8, 13, 14, 15, 18, and 22. In our 15 cases, immunohistochemistry favored a distal tubule origin (EMA⁺, AE1/AE3⁺, CK7⁺, CK19⁺, E-cadherin⁺, AMACR⁺, and CD10⁻). Prognosis was favorable in our cases, while in the literature, two metastatic cases were reported. Further investigations are required to determine the frequency and true prognosis of these tumors, which are easily identifiable morphologically.     

原发性皮肤黏液癌3例临床病理观察及文献复习

目的：探讨原发性皮肤黏液癌的临床病理学特点及预后。方法：通过临床资料总结、病理形态学观察、免疫表型分析,并复习文献资料。结果：皮肤原发性黏液癌直径0.3~15 cm不等,生长缓慢,病程常为数月至数十年。组织学上,表皮完整,肿瘤主要位于真皮层,并常累及皮下脂肪组织,大量黏液形成黏液湖,纤细的纤维将黏液湖分隔成多房性、蜂窝状。黏液湖中可见散在岛状、簇状、小腺样肿瘤上皮团。肿瘤细胞小,呈立方形,胞浆丰富,细胞核小,未见核分裂。免疫组化：癌细胞例1：CEA、EMA、ER、PR、P53、CK7、GCDFP-15(+),TTF-1、S-100、CK20(?)。例2：CEA、EMA、P53、CK7、GCDFP-15(+),ER、PR、TTF-1、S-100、CK20(?),Ki-67低表达(1%~3%)。例3：CEA、EMA、CK7、GCDFP-15(+),P53、ER、PR、TTF-1、S-100、CK20(?), Ki67(+<10%)。结论：原发于皮肤的黏液癌少见,好发于老年男性的头面部,组织学上与转移性黏液癌鉴别困难,须结合临床及免疫组化标记排除转移癌后方可诊断。免疫组织化学多表达CK7、GCDFP-15、EMA、CEA,Ki67阳性率低<10%。治疗主要采用手术局部扩大切除肿瘤,预后较好。     

Papillary carcinoma of the thyroid gland and atresia of the common bile ducts of a five year old boy

Summary We present a case of papillary carcinoma of the thyroid gland with pulmonary metastases in a 5 year old boy. The child also suffered from atresia of the gallbladder and the common bile ducts with biliary cirrhosis of the liver and died from hepatic insufficiency. Possible correlations between childhood thyroid carcinoma and congenital malformations are discussed.     

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) was first described by Chan et al in 1991. It is characterized by nest or strands of epidermoid tumor cells with squamous differentiation, rare mucous cells, prominent sclerotic stroma, eosinophilic and lymphoplasmacytic infiltration, and a background of chronic lymphocytic thyroiditis in the non-neoplastic thyroid gland. It is important to recognize SMECE of thyroid and differentiate it from squamous cell carcinoma or other neoplasms with squamous differentiation/metaplasia. In published cases, the SMECE of thyroid gland predominantly occurs in women. We report a case of SMECE of thyroid in a 45-year-old male patient. All cases in male patients were Caucasian described in English literature, and our case is the first one in Asian.     

Differentiation of ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma by immunostaining with beta-catenin

AIMS: To investigate whether localization of beta-catenin is helpful in differentiating primary ovarian mucinous carcinoma and colorectal adenocarcinoma metastatic to the ovary. Extra-ovarian cancers which metastasize to the ovaries, especially from colorectal adenocarcinoma, frequently mimic primary ovarian carcinomas, particularly endometrioid and mucinous types. Distinguishing primary ovarian carcinoma from metastatic colorectal carcinoma is important for both therapeutic and prognostic reasons. Even after thorough histological examination, metastatic colorectal adenocarcinomas are still often mistaken for primary ovarian adenocarcinomas. Although some tumour makers have been advocated and are helpful in most cases, sometimes the distinction between primary mucinous carcinoma and metastatic colorectal carcinoma remains a problem. Activation of Wnt signalling through mutations of APC or beta-catenin is a key event in the development of colorectal cancer. These mutations lead to nuclear localization of beta-catenin, which can be demonstrated immunohistochemically. METHODS AND RESULTS: Formalin-fixed paraffin-embedded specimens from 43 primary ovarian mucinous carcinomas and 23 metastatic colorectal adenocarcinomas were included in this study. Sections were immunostained with antibodies to beta-catenin, cytokeratin (CK)7, CK20 and carcinoembryonic antigen (CEA). Nuclear localization of beta-catenin was found in 83% (19/23) of metastatic colorectal cancers and 9% (4/43) of ovarian mucinous carcinomas. Ovarian mucinous carcinomas were usually positive for CK7 (34/43, 79%). For comparison, 40 non-mucinous carcinomas of the ovary and 42 metastatic adenocarcinomas from other organs were also immunostained with antibodies against beta-catenin. Although nuclear localization of beta-catenin was occasionally seen in non-mucinous carcinoma of the ovary and metastatic adenocarcinoma from other organs, such tumours were usually distinguishable by their clinicopathological picture and rarely raised diagnostic problems. CONCLUSIONS: Immunostaining of beta-catenin is a useful marker for differentiating between ovarian mucinous carcinoma and metastatic colorectal adenocarcinoma.