Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla of Vater: A case report with immunocytochemical analyses

Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma components comprising at least 30% of either components. MANEC occurring in the ampulla of Vater is extremely rare, and only 16 cases have been reported in the English language literature. In the present report, we describe the first case of MANEC of the ampulla of Vater with immunocytochemical analyses. An 82‐year‐old Japanese male was incidentally found to have a tumorous lesion in the ampulla of Vater. Endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) of the tumor was performed. The Papanicolaou smear demonstrated the presence of different three components. The most dominant component was cohesive clusters of small round cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which corresponded to small cell carcinoma. The second component was an adenocarcinoma, which was composed of irregularly overlapping clusters of tall columnar cells with large round to oval nuclei containing conspicuous nucleoli. The third component was an adenoma, which was comprised of flat cohesive clusters of columnar cells without atypia. Immunocytochemical analyses demonstrated that synaptophysin was expressed in the small round cells, and cdx‐2 was expressed in all three components. Accordingly, a cytodiagnosis of MANEC with adenoma component was made. Preoperative diagnosis of ampullary MANEC is difficult. However, this report clearly demonstrates three different components in the EUS‐FNA cytological specimen. Therefore, we suggest that cytological examination is a useful method for diagnosis of MANEC of the ampulla of Vater.     

A case of mixed adenoneuroendocrine carcinoma of the gallbladder arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction

A 54‐year‐old Japanese woman was referred with a gallbladder tumor. Based on the results of the computed tomography scan, endoscopic retrograde cholangiopancreatography, and magnetic resonance cholangiopancreatography, a mucin‐producing neoplasm of the gallbladder associated with pancreaticobiliary maljunction was diagnosed. Extended cholecystectomy, extrahepatic bile duct resection, and choledochojejunostomy were performed, and she remains free of recurrence 24 months after resection. Histopathological examination revealed that the papillary component of the lesion was an intracystic papillary neoplasm with diverse characteristics of pancreaticobiliary epithelium and intestinal epithelium including mucin. In this component, most of the papillary lesion was a high‐grade intraepithelial neoplasm, but also showed slight invasion into the muscular layer. The nodular component consisted of both poorly differentiated biliary type adenocarcinoma and large cell neuroendocrine carcinoma. We report a rare case of a mixed adenoneuroendocrine carcinoma arising from an intracystic papillary neoplasm associated with pancreaticobiliary maljunction. As for the histogenesis of this tumor, based on the histopathologic appearance, transdifferentiation from poorly differentiated biliary type adenocarcinoma to large cell neuroendocrine carcinoma is considered the most possible histogenesis of this tumor.     

Clinicopathological features of an ascending colon mixed adenoneuroendocrine carcinoma with clinical serosal invasion

Mixed adenoneuroendocrine carcinoma (MANEC) is exceedingly rare with a poor outcome. In this article, we reported a MANEC in a 68-year-old woman with a symptom of abdominal pain and distension. MANEC derived from the ascending colon with highly aggressive behavior. The diagnosis and distinguish of MANEC must base on histological findings and immunohistochemical findings. In this case, microscopic observation showed tumor cells were arranged in conglobate and nested by fibrous tissue with a visible cell atypia and mitotic. NEC-like and exocrine glandular cells were also been seen in a single neoplasm. MANEC tissues were immunopositive for CK, CK20, P53, CK7, CDX-2, Ki-67 (70%+), E-cad, CD56, CEA, Syn, villin and CgA, and immunonegative for CA125, NSE, ER and PR. Here, the patient was treated by surgical operation and was followed-up near 3 months, no local recurrence and distant metastasis.     

Cytological findings of appendiceal mixed adenoneuroendocrine carcinoma in pleural effusion: Morphological changes evident after metastasis

Goblet cell carcinoid (GCC) of the appendix is now regarded as a malignant tumor, and mixed adenoneuroendocrine carcinoma (MANEC) is a carcinoma progressing from GCC. We describe a man initially diagnosed with GCC of the appendix who died 4 years after diagnosis. Pleural fluid due to metastasis was noted in the terminal phase. Histological findings of the initial tumor indicated that cells with signet‐ring morphology were predominant, but the cytological morphology of the fluid was more atypical, making it difficult to diagnose as metastatic GCC by cellular morphology alone. The cells in the pleural fluid were immunopositive for synaptophysin, which was compatible with GCC, but p53 and ki67 staining indicated that the metastatic tumor was more aggressive. These findings suggested a final diagnosis of poorly differentiated adenocarcinoma‐type MANEC, which we define as a tumor with typical GCC characteristics and foci that cannot be distinguished from a poorly differentiated adenocarcinoma. This case, which we believe is reported here for the first time, indicates the cytological features of GCC cells may change at metastatic sites to be more atypical and aggressive as the tumor progresses, and these changes should be considered in diagnosis. Diagn. Cytopathol. 2015;43:577–580. © 2014 Wiley Periodicals, Inc.     

An extremely rare case of Epstein‐Barr virus‐associated gastric carcinoma with differentiation to neuroendocrine carcinoma

Epstein‐Barr virus (EBV)‐associated gastric carcinoma (EBVGC) is defined as a neoplasm comprising monoclonal proliferation of EBV‐infected gastric epithelial cells. Although the typical histology is gastric carcinoma with lymphoid stroma (GCLS), the histologic features of the tumor vary. We report herein the case of a 78‐year‐old man with multiple simultaneous EBVGCs revealing different histopathologic morphologies; one was mixed adenoneuroendocrine carcinoma (MANEC), and the other was GCLS. Both tumor types exhibited positive results for EBV in situ hybridization. To the best of our knowledge, this represents the first report of EBVGC showing neuroendocrine differentiation. Immunohistochemistry also revealed a loss of gastrointestinal features, including CDX2, MUC5AC, and MUC6 expression, among tumor cells from the neuroendocrine component of the MANEC. We describe the pathologic features of this rare neoplasm and discuss the mechanisms underlying the neuroendocrine differentiation of EBVGC cells, along with providing a brief review of the literature.     

Mixed adenoneuroendocrine carcinoma of the gallbladder with squamous cell carcinomatous and osteosarcomatous differentiation: Report of a case

An extremely rare case of mixed adenoneuroendocrine carcinoma (MANEC) of the gallbladder is reported, in which the tumor showed diverse differentiation toward neuroendocrine tumor (grade 2), tubular adenocarcinoma, squamous cell carcinoma, and, in addition, osteosarcoma. The patient was an 80‐year‐old man, who underwent cholecystectomy because of a large polypoid tumor filling the gallbladder lumen. The tumor consisted of an intimate admixture of neuroendocrine tumor (grade 2) and tubular adenocarcinoma, and, in many areas, cell nests of neuroendocrine tumor appeared to bud off from tubular structures of the adenocarcinoma, in a manner resembling the ‘ductulo‐insular complex’ seen in nesidioblastosis of the pancreas. Small areas of squamous cell carcinoma were also found. The stroma consisted of a dense proliferation of atypical spindle cells showing focal osteosarcomatous differentiation, and an apparent transition from an epithelial tissue component to atypical spindle cells was observed. Immunohistochemically, neuroendocrine cells were positive for synaptophysin, chromogranin A, and serotonin, and the sarcomatoid stroma was partly immunoreactive for cytokeratin. The present case is the first example of MANEC of the gallbladder with simultaneous squamous cell carcinomatous and osteosarcomatous differentiation. ‘Neometaplasia’ of carcinoma cells in diverse directions was considered the most plausible explanation for the formation of this multifaceted neoplasm.     

Mixed adenoneuroendocrine carcinoma of the gallbladder,amphicrine type: Case report and review of literature

Amphicrine type mixed adenoneuroendocrine carcinoma (MANEC), also known as amphicrine carcinoma, is an exceedingly rare neoplasm comprising of tumor cells simultaneously demonstrating both neuroendocrine and exocrine differentiation. Majority of reported cases were found in tubular gastrointestinal tracts such as colon. Herein, we report the first case of amphicrine carcinoma in gallbladder in a 57-year-old female who presented with abdominal pain, vomiting, and gallbladder mass on imaging followed by radical cholecystectomy. Macroscopically, the tumor was a polypoid solid mass with a firm and tan-white cut surface located at the gallbladder fundus. Histologically, the tumor cells were composed of monotonous-appearing signet-ring cells with fine chromatin, variably conspicuous nucleoli, brisk mitotic figures, and spotty necrosis. They were loosely clustered, forming nests and cords but no glandular formation. Immunohistochemically, the entire tumor showed strong and diffuse immunoreactivity for CDX2, p53, and synaptophysin, with patchy positivity for CD56, chromogranin, and INSM1. Kreyberg stain highlighted both intracytoplasmic and extracellular mucin. Ki-67 proliferation index was approximately 70%. Next-generation sequencing performed on a 724 cancer-related gene panel identified TP53 mutation at c.844C>T (p.R282W). To our knowledge, this is the first case of amphicrine carcinoma in gallbladder. It highlights the complex dynamism and controversial pathogenesis of this unique entity, the exact mechanism and clinicopathologic behavior of which are not yet understood.     

Neuroendocrine liver metastasis in gastric mixed adenoneuroendocrine carcinoma with trilineage cell differentiation: a case report

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare disease, which mostly occurs in the gastroin testinal tract and pancreas. Here we report a case of gastric MANEC with tri-lineage differentiation in which only the neuroendocrine component had metastasized to the liver. Liver and gastric masses were detected by abdominal computed tomography, and the preoperative relationship between liver and gastric masses was unknown. The histopathological analysis after operation confirmed the gastric mass to be MANEC, whereas the liver mass was actually the metastatic neuroendocrine component of the gastric MANEC. In the pathologic diagnosis, tri-lineage differentiation, including tubular adenocarcinoma, neuroendocrine carcinoma and squamous cell carcinoma was observed in the gastric MANEC tissues. The mitotic and Ki-67 labeling indexes of the resected tumor tissue were high, and thus, the tumor was classified as a grade G3 neuroendocrine carcinoma, which has a poor prognosis. Multiple low-density masses were found in the right lobe of the liver 2.5 months after operation.     

Amphicrine (mixed adenoneuroendocrine carcinoma) of the duodenum and coexistent metastatic well differentiated neuroendocrine tumour

A 56-year-old man with a clinical history of pancreatitis was diagnosed with a periampullary carcinoma during investigation for increase of liver enzymes. Biopsies confirmed an adenocarcinoma. A Whipple resection showed an amphicrine carcinoma and a metastatic neuroendocrine tumour to the peripancreatic lymph nodes. High-grade amphicrine carcinoma did not spread to nodes. It is unlikely that the well differentiated tumour is part of the duodenal amphicrine carcinoma but rather from a separate, undetected well differentiated neuroendocrine carcinoma located elsewhere.This case highlights an unusual combination of neuroendocrine tumours.     

Hepatocellular carcinoma in nonalcoholic fatty liver disease mimicking benign hemangioma: two case reports and literature review

Objective: To study the clinical features of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC). Methods: The clinical manifestations, imaging features, pathological subtypes and treatment outcome of two cases with NAFLD-associated HCC were analyzed. Results: In these two cases, both were young, obese male patients, with contrast enhanced CT scan of hemangioma-like features. They had undergone surgical resection and both were reported as well-differentiated HCC pathologically. They were followed-up respectively up to 46 and 36 months post-operatively with no evidence of recurrence or metastasis. Conclusions: NAFLD-associated HCC has different radiological presentations from typical HCC. Incidental finding of any liver occupying lesions in NAFLD patients should raise immediate clinical attention.     

Metastatic mixed acinar‐neuroendocrine carcinoma of the pancreas to the liver: A cytopathology case report with review of the literature

A case of metastatic mixed acinar‐neuroendocrine carcinoma (MANEC) of the pancreas to the liver is reported. A diagnostic percutaneous US‐guided FNA and core biopsy of a liver nodule was performed. The FNA smears were cellular and showed neoplastic cells in clusters with acinar formation, isolated single cells, and scattered naked nuclei. The cytoplasm was finely granular. The nuclei were relatively uniform, some with speckled chromatin and prominent nucleoli. The immunohistochemistry performed on the cell block showed strong positivity for cytokeratin AE1/AE3, chromogranin, and synaptophysin. Furthermore, the tumor cells were weakly positive for α1‐antichymotrypsin. The Ki‐67 mitotic index was up to 50%. Based on the morphology and supporting immunohistochemical stains, the final cytopathologic diagnosis rendered was “Positive for malignant cells. Carcinoma with mixed acinar and endocrine features.” To our knowledge, this is the first report of a metastatic MANEC to the liver diagnosed based on cytology with confirmatory histology. The difficulties in the cytopathologic diagnosis and differential diagnosis of MANEC are discussed in this article. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Cytological features of chondroblastoma: a case report with review of the literature

Chondroblastoma is an uncommon benign tumor of bone with a characteristic epiphyseal location. This report documents the cytological features on fine-needle aspiration biopsy (FNAB) of a chondroblastoma which appeared as a lytic lesion, predominantly in the metaphysis of the medial condyle of right femur in a 20-year-old male. Smears characteristically revealed hyper- to hypocellular lobules comprising small round to polyhedral cells (chondroblasts) embedded in an abundant myxoid stroma. The cytological diagnosis of chondroblastoma was confirmed on histopathology. The radiological appearance and differential diagnosis in this case is discussed.     

Cytological challenges in the diagnosis of intrathyroidal parathyroid carcinoma: A case report and review of literature

Parathyroid carcinoma is an uncommon malignancy and the probability of an intrathyroidal location is low. Fine needle aspirations (FNA) of these presumably “thyroid nodules” can lead to misinterpretation because of the similarities in cytological features of parathyroid and thyroid lesions. Despite limitations, USG guided FNA cytology remains the first line of investigation. We report a case of intrathyroidal parathyroid carcinoma presenting with hypercalcemia and elevated serum parathormone. Cytological findings attributed it to a possible parathyroid lesion and histopathology revealed a parathyroid carcinoma. It is reported due to its rare occurrence on FNA along with brief literature review.     

Cytological features of warthin‐like papillary thyroid carcinoma: A case report with review of previous cytology cases

Warthin‐like papillary thyroid carcinoma (WLPTC) is a rare morphological variant of papillary thyroid carcinoma which mimics various benign and malignant lesions on thyroid aspiration cytology. As correct cytological diagnosis is the cornerstone for appropriate patient management, awareness of the salient cytomorphological characteristics of this tumor is essential. Here, we present cytological features of a case of WLPTC along with discussion of the common differential diagnoses and a brief review of the literature to ascertain the most consistent cytological findings of WLPTC. The present case also harboured BRAFV600E mutation which is the commonest molecular alteration seen in WLPTC.     

Cytological features of dyshormonogenetic goiter: case report and review of the literature

Dyshormonogenetic goiter is a rare cause of congenital goiter occurring due to a lack of enzymes necessary for the synthesis of thyroid hormones. We present a case of dyshormonogenetic goiter diagnosed on cytology. Correlation with the history, clinical findings, levels of thyroid hormones and other investigations is imperative for the diagnosis. The degree of hyperplasia is severe enough to prompt a diagnosis of malignancy, particularly follicular neoplasm. An accurate diagnosis helps to constitute proper therapy and prevents surgery.     

Low-grade endometrioid carcinoma of the ovary associated with undifferentiated carcinoma: case report and review of the literature

The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma.     

Primary mixed lymphoepithelioma-like carcinoma and intra-hepatic cholangiocarcinoma: a case report and review of literature

Primary lymphoepithelioma-like carcinomas (LELC) of the hepatobiliary tract are quite rare and the majority are associated with the Epstein-Barr virus (EBV). Here we report an unusual case of intrahepatic cholangiocarcinoma (ICC), admixed with LELC in a 63 year-old Filipino woman who presented clinically with right flank and back pain. Histologically, the tumor showed a dense lymphocytic infiltrate, predominantly composed of CD3 (+) T cells, and two components: an undifferentiated carcinoma, morphologically similar to nasopharyngeal carcinoma, and a poorly differentiated ICC intimately admixed. Immunohistochemical studies revealed that both components were immunoreac-tive for AE1/AE3, cytokeratin 7 and, focally, for monoclonal CEA. Both components were negative for cytokeratin 20 and HePar 1. EBER-1 in situ hybridization was uniformly positive in the tumor cells. The presence of EBV in ICC and LELC suggests that the virus may be linked to the pathogenesis of both components of the tumor. The mechanism of virus-driven neoplastic transformation needs further study.     

Cytological features of atypical polypoid adenomyoma of the endometrium: A case report with literature review

Atypical polypoid adenomyoma (APA) is a rare mixed epithelial and mesenchymal tumor characterized histopathologically by the presence of disorganized hyperplastic glands with cytological atypia embedded in intersecting fascicles of fibromuscular stromal cells. Herein, we report the first documented endometrial cytological case of APA. A 35‐year‐old Japanese female presented with irregular menstrual cycles and then was found to have polypoid lesions of the endometrium. Cytological examination of the endometrium and endometrial curettage were performed. The Papanicolaou smear revealed the presence of abundant clusters of crowded glandular cells in a clean background. These clusters exhibited irregular branching and dilatation, and these glandular cells had mild to moderately enlarged round to oval nuclei. Within the dilated glands, metaplastic squamous cells (squamous morules) were observed. The most striking feature was the presence of short fascicles of the spindle cells without atypia around the dilated atypical glandular cell clusters with squamous morules. Histopathological and immunohistochemical examinations revealed a diagnosis of APA. Our report demonstrates that the characteristic cytological feature suggestive of APA is the presence of short fascicles of the spindle cells without atypia surrounding dilated atypical glandular cell clusters with squamous morules in a clean background, and their appearance can allow cytologists/cytopathologists to consider APA in differential diagnosis in the endometrial cytological specimens. Diagn. Cytopathol. 2017;45:345–349. © 2016 Wiley Periodicals, Inc.     

超声结合血清学指标在壶腹癌与胰头癌鉴别诊断中应用

目的探讨超声与血清学检查联合应用在壶腹癌与胰头癌鉴别诊断中的价值。方法选择2013年2月至2018年10月在福建医科大学附属协和医院住院手术经病理检查证实的壶腹癌49例,其中男性29例,女性20例;年龄39~77岁,平均年龄59.1岁。经病理检查证实胰头癌63例,其中男性38例,女性25例,年龄35~79岁,平均年龄60.6岁。外科手术前1周内行腹部超声检查和血液肿瘤标记物Ca19-9、血生物化学检查[总胆红素(TBiL)、直接胆红素(DBiL)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)],分析两组患者的血清学指标和超声声像图特征。结果壶腹癌与胰头癌均多见于中老年男性,胰头癌组Ca19-9>200 U/mL所占比率高于壶腹癌组,而壶腹癌组TBiL、DBiL、AST、ALP测值升高的比率高于胰头癌组。壶腹癌组病灶平均最大径(2.42 cm)小于胰头癌组(3.92 cm),壶腹癌组发生肝内外胆管扩张的比率(95.9%)高于胰头癌组(69.8%)。壶腹癌与胰头癌多呈较均质的低回声病灶,乏血液供应,但胰头癌病灶形态更不规则,边界不清,常侵犯周围血管组织。术前超声对壶腹癌与胰头癌的诊断准确率分别为46.94%、100.00%。结论壶腹癌与胰头癌在超声表现与血液学指标方面存在一定的差异,超声检查时应综合分析判断,对于提高术前诊断率,为临床制定诊疗方案具有重要意义。