Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla: Two case reports with review of literature

Mixed adenoneuroendocrine carcinoma (MANEC) of ampulla is rare, with only 13 cases reported, and the diagnoses were all based on histology mostly after surgery. We describe two new cases with cytological features of signet ring‐cell carcinoma mixed with small‐cell carcinoma, and intestinal adenocarcinoma mixed with large‐cell neuroendocrine carcinoma. Our cases and literature review demonstrate the higher frequency of periampullary‐duodenum subtype in MANEC compared with non‐MANEC ampullary carcinomas. In accordance, of the 14 MANEC cases with detailed morphology available, the most common glandular components are intestinal‐type carcinoma (6/14), followed by goblet carcinoid tumor (3/14), signet ring‐cell carcinoma (2/14), pancreatobiliary‐type carcinoma (2/14), and pancreatic acinar cell carcinoma (1/14). The intestinal‐type carcinoma and goblet carcinoid in MANEC are favorable histological types showing no distant metastasis or mortality (0/9) during 6–36 months follow‐up. In contrast, the signet ring cell, pancreatobiliary‐type carcinoma, and acinar cell carcinoma are unfavorable with distant metastatic rate and mortality rate of 80% (4/5) during 3–16 months follow‐up. The combination of favorable glandular histological types with high‐grade neuroendocrine tumors (neuroendocrine carcinoma) has a mortality rate of 0% (0/3), whereas the combination of unfavorable glandular types with low‐grade neuroendocrine tumors (e.g., carcinoid, atypical carcinoid) has a mortality rate of 100% (3/3). In addition, younger age (<40 years) seems to be associated with high mortality rate of 100% (2/2). Overall, cytology preparations are able to make the diagnosis of MANEC and distinguish the subcomponents. Disease progression is apparently driven by the carcinomatous component of the tumor. Diagn. Cytopathol. 2014;42:1075–1084. © 2014 Wiley Periodicals, Inc.     

Mucin‐producing gallbladder adenocarcinoma with focal small cell and large cell neuroendocrine differentiation associated with pancreaticobiliary maljunction

Herein is reported a case of mucin‐producing carcinoma of the gallbladder in a 55‐year‐old Japanese woman. Although the patient's status and laboratory data initially suggested biliary pancreatitis due to gallstone, radiography and endoscopy confirmed the presence of pancreaticobiliary maljunction and a gallbladder tumor with excessive mucin, in which the duodenal papilla and the common bile duct were impacted. Following surgery, the gallbladder tumor was histopathologically diagnosed as a mixed endocrine–exocrine carcinoma. The carcinoma predominantly consisted of papillary, but also contained some tubular adenocarcinomatous components. Additionally, small foci of small cell and large cell neuroendocrine carcinomatous components were observed. There was no evidence of lymph node metastasis, distant metastasis, or direct invasion outside the gallbladder. Thus, the final classification of pT2N0M0 stage II was given to this lesion, according to the Union Internationale Contre le Cancer guidelines. The postoperative course was uneventful, and the carcinoma had not recurred in the absence of chemoradiotherapy for a period of 20 months. Mucin‐producing gallbladder carcinoma is a rare clinical condition that can occur in patients with pancreaticobiliary maljunction. Detailed investigation of this condition is important to develop and refine effective therapeutic strategies.     

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.     

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.     

Bile duct carcinoma involving the common channel associated with pancreaticobiliary maljunction shows an extension pattern similar to ductal carcinoma of the pancreas

Biliary tract cancer occurs frequently in patients with pancreaticobiliary maljunction (PBM), although no details of its clinicopathological characteristics have been reported. Here we describe a case of bile duct (BD) cancer that developed in association with PBM. This BD cancer involved the common channel, extended to the main pancreatic duct (MPD) via the common channel, and invaded the pancreatic parenchyma, where its growth and spread, and features of its recurrence, were similar to those of ductal carcinoma of the pancreas. We assumed that MPD extension of BD cancer via the common channel was the reason for its deep spread to the pancreas, since BD cancer usually spreads along the BD and rarely reaches the common channel of the ampulla of Vater. During the follow‐up of patients with PBM, attention should be paid to involvement of the common channel by BD cancer and also to cancer developing silently in the pancreas after extrahepatic BD resection.     

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.     

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.     

Intraductal papillary neoplasm of the bile duct,gastric type,arising in the intrapancreatic common bile duct could progress to colloid carcinoma: report of a case

Intraductal papillary neoplasm of the bile duct (IPNB) exists in a pathway of multistep-carcinogenesis toward cholangiocarcinoma. Four subtypes are observed in IPNB, pancreatobiliary type, intestinal type, gastric type, and oncocytic type, similarly to the corresponding disease in the pancreas, intraductal papillary mucinous neoplasm (IPMN). IPNB can present with or without macroscopically visible mucin secretion. IPNB usually progresses to tubular adenocarcinoma. However, there are a limited number of well-described cases of gastric-type IPNB progressing not to tubular adenocarcinoma but to colloid carcinoma. Herein, we present a case of an 82-year-old female patient with gastric-type IPNB in the intrapancreatic common bile duct without macroscopically visible mucin secretion, which progressed to colloid carcinoma. As IPNB, especially without visible mucin secretion, is considered to be a heterogeneous group of diseases, such an unexpected association could occur.     

Encapsulated apocrine papillary carcinoma of the breast: Case report with clinicopathologic and immunohistochemical study

We describe a case of encapsulated papillary carcinoma (EPC), apocrine variant in a 50‐year‐old woman. The patient presented a cystic lesion in her right breast, measuring 8 cm in diameter, containing three solid papillary nodules. A fine‐needle aspiration showed isolated apocrine cells containing round nuclei, irregular nuclear membranes, fine chromatin, and prominent macronucleoli. The lesion was excised and showed a pure papillary apocrine carcinoma, which stained diffusely with GCDFP‐15 and androgen receptors. The lesion was totally devoid of myoepithelial cells (smooth muscle actyn, p63, calponin, and collagen IV stains were negative). With MIB1 the proliferative activity was 10%. To the best of our knowledge, this is the first report of EPC apocrine variant with cytologic and immunohistochemical study. This lesion must be included in the list of apocrine lesions of the breast. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Pseudomyxoma peritonei (mucinous carcinoma peritonei) preceded by intraductal papillary neoplasm of the bile duct

Pseudomyxoma peritonei (mucinous carcinoma peritonei) is a rare clinical disease. Although most cases derive from appendiceal mucinous tumors, a few are associated with pancreatic intraductal papillary mucinous neoplasms. Intraductal papillary neoplasms of the bile duct share many similarities with pancreatic intraductal papillary mucinous neoplasms and are thought to be their biliary counterparts. We report a case of low-grade intraductal papillary neoplasm of the bile duct who developed pseudomyxoma peritonei 6 years after surgical treatment of the primary biliary tumor. To the best of our knowledge, this is the first case of pseudomyxoma peritonei associated with intraductal papillary neoplasm of the bile duct. The tumor recurrence in our case may be due to tumor spillage at the time of the first surgery, since there is no recurrent biliary tumor in the preserved liver lobe. Prevention of spillage of epithelial cell-containing mucin during surgical operations is important in treating intraductal papillary neoplasms of the bile duct.     

Intraductal papillary neoplasm of the bile duct associated with Clonorchis sinensis infection

Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-alpha. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.     

Hobnail variant of papillary thyroid carcinoma: A case with an unusual presentation

Variants of papillary thyroid carcinoma (PTC) account for up to 25% of the cases, some of which are proven to be associated with aggressive clinical behavior such as tall cell and columnar cell variants. Hobnail variant of PTC (HVPTC) is recently described as a rare and aggressive variant of PTC. Herein, we are reporting a case of HVPTC in a patient who presented with hemoptysis and an intratracheal blood clot that was aspirated and submitted for cytopathological examination. Cytomorphology displayed neoplastic cells with profound micropapillary architecture, elongated nuclei, and prominent hobnail configuration. Nuclear features of PTC such as pseudoinclusions, nuclear overlapping, crowding, and grooves were readily identified. Subsequent total thyroidectomy revealed a 1.4 cm PTC with columnar and hobnail components. HVPTC is a rare locally aggressive subtype, which may present with metastasis from an occult thyroid primary. HVPTC needs to be included in the differential diagnosis of metastatic carcinoma with micropapillary architecture on fine needle aspiration, particularly in head and neck area. Diagn. Cytopathol. 2017;45:754–756. © 2017 Wiley Periodicals, Inc.     

Update on follicular variant of papillary thyroid carcinoma with an emphasis on new terminology: noninvasive follicular thyroid neoplasm with papillary-like nuclear features

The most common papillary thyroid carcinoma (PTC) variant is the follicular variant, representing ∼30% of all PTCs. The tumour is most common in middle aged (4th – 5th decades) women, who usually present with a single dominant nodule (about 3 cm). By definition, follicular architecture must be the dominant finding, while demonstrating the nuclear features of PTC. Papillary structures are <1% of volume, while necrosis, increased mitoses (>3/10 high power fields) and psammoma bodies are absent. The tumour category is divided into “encapsulated/well demarcated” and “invasive” types. The nuclear features include enlarged, elongated and overlapping nuclei; membrane irregularities (irregular contours, grooves and pseudoinclusions); chromatin clearing, margination and glassy nuclei. When the tumour is encapsulated/well demarcated without invasion, demonstrating the other inclusion and exclusion criteria, the new name of “Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features” (NIFTP) is used, a tumour that requires no additional treatment.     

Intraductal papillary neoplasm arising from peribiliary glands connecting with the inferior branch of the bile duct of the anterior segment of the liver

Intraductal papillary neoplasms of the bile duct are generally thought to arise from neoplastic papillary proliferation of epithelial cells lining the bile duct. We herein report a case with findings that strongly suggested that the biliary cystic tumor might have derived from a peribiliary gland. A 69-year-old female was found to have a cystic lesion with intracystic protrusions at the anterior segment of the right hepatic lobe and underwent hepatic anterior segment resection. Fluoroscopy of the resected specimen injected with contrast medium into the cyst revealed a connection between the cystic lesion and the bile ducts. The cyst was multilocular in appearance. On microscopic examination, the cyst was located within the portal tract of the inferior branch of the anterior segment and connected with the inferior branch of the bile duct. The wall of the hepatic cyst lacked an ovarian-like stroma. The tumor was composed of papillary and glandular components, and the tumor cells were similar to gastric foveolar and pyloric gland epithelia and regarded as adenoma. These tumor cells were positive for MUC 5AC, MUC6, and HIK1083. The tumor was finally diagnosed as an intraductal papillary neoplasm of the bile duct (adenoma, gastric type) arising from a peribiliary gland.     

Bone morphogenetic protein‐2 expression in an intraductal papillary mucinous neoplasm with marked ossification: A case report

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56‐year‐old Japanese man was under follow‐up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non‐invasive and invasive lesions expressed bone morphogenetic protein‐2 (BMP‐2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP‐2 in the present case.     

甲状腺乳头状癌细针穿刺涂片中BRAF(VE1)的表达及其临床意义

目的探讨甲状腺细针穿刺涂片免疫细胞化学染色与甲状腺乳头状癌颈部淋巴结转移和多灶性发生之间的关系。方法收集甲状腺细针穿刺涂片诊断为甲状腺乳头状癌或可疑甲状腺乳头状癌合计89例,记录其手术标本中的病灶数量及是否淋巴结转移,细胞涂片褪色后行BRAF(VE1)免疫细胞化学染色,对染色结果与淋巴结转移及肿瘤多灶性的关系进行分析。结果 89例涂片中检出BRAF阳性51例,阴性38例。BRAF阳性组与阴性组间淋巴结转移率差异有显著性(χ~2=47.352,P0.05),一致性检验κ值为0.733;BRAF阳性组与阴性组间多灶性发生率差异有显著性(χ~2=19.177,P0.05),一致性检验κ值为0.445。结论甲状腺细针穿刺涂片BRAF免疫细胞化学染色对甲状腺乳头状癌颈部淋巴结转移和肿瘤多灶性发生具有一定的预测价值,有望成为术前评估淋巴结转移风险的指标。     

Composite metastatic carcinoma in lymph nodes of patients with concurrent medullary and papillary thyroid carcinoma: A report of two cases

Synchronous occurrence of medullary and papillary carcinoma of the thyroid gland is very rare. We describe two cases of synchronous medullary and papillary carcinoma of the thyroid. In both cases, medullary carcinoma and papillary carcinoma were separate in the thyroid but mixed in some of the lymph node metastases. A review of the literature and our own cases revealed that composite medullary and papillary carcinoma metastases in the lymph nodes is a common feature of patients with synchronous medullary and papillary carcinoma of the thyroid gland.     

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.     

Intraductal papillary mucinous neoplasm (IPMN) of the gastric-type with focal nodular growth of the arborizing papillae: a case of high-grade transformation of the gastric-type IPMN

We present a case of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, demonstrating a process of high-grade transformation of the gastric-type IPMN. An 83-year-old Japanese woman underwent pylorus-preserving pancreatoduodenectomy for removal of a multicystic mass of the pancreas head, which had been followed up for 7 years. The removed tumor was a low-grade gastric-type IPMN spreading in the branch ducts, focally forming an intraluminal nodular lesion. The nodular lesion was comprised of arborizing papillotubular proliferation of cuboidal to columnar epithelia with high-grade atypia, and was characterized by diffuse MUC1 expression and a gastric mucin phenotype (focal MUC5AC and MUC6 expressions). Therefore, the nodular lesion was consistent with the pancreatobiliary-type IPMN, and the present case suggests that the low-grade gastric-type IPMN may progress to a focal intraductal carcinoma over the years, and the pancreatobiliary-type IPMN may be one of the forms of such high-grade transformation of the gastric-type IPMN. One of the cystic lesions was an oligocystic-type serous cystic neoplasm (serous cystadenoma), which might be an incidental concomitance or have a common basis.