Mitsuaki Ishida

Lymphoepithelial cyst with sebaceous glands of the pancreas: a case report

BackgroundLymphoepithelial cyst (LEC) of the pancreas is a rare benign tumor. LEC with sebaceous glands of the pancreas is extremely rare, and its histogenesis remains unclear.Case presentationWe present a 66-year-old man with an incidental finding of a cystic lesion at the neck of the pancreas. Pancreatic juice cytology results and elevated serum carbohydrate antigen 19-9 and Dupan-2 levels indicated that the cyst was a potential adenocarcinoma. Therefore, a pancreaticoduodenectomy was performed. Macroscopically, the tumor was a unilocular cyst with a thin transparent wall, filled with soft yellow material. Pathological findings showed that the cyst was lined with squamous epithelium, accompanied by dense lymphoid tissue with scattered germinal centers. There were no hair follicles, but sebaceous glands were present in the lymphoid tissue just beneath the squamous epithelium. Therefore, the histopathological diagnosis was an LEC with sebaceous glands of the pancreas. Furthermore, the squamous epithelium surrounding the cyst was pathologically continuous with the tubular structure, indicating that the tubular structure transitioned into the squamous epithelium.ConclusionsWe report an extremely rare case of LEC with sebaceous glands of the pancreas. Moreover, the pathological findings, which showed that the tubular structure transitioned into the squamous epithelium, suggested that this was squamous metaplasia. In order to investigate the histogenesis of LEC of the pancreas, the pathological findings must be evaluated.

Mucinous carcinoma occurring in the ceruminous gland

To the Editor: Malignant tumors occurring in the external auditory canal are rare, representing less than 0.2 % of all head and neck cancers. Squamous cell carcinoma is the most common histological subtype, and the occurrence of adenoid cystic carcinoma has also been reported. The external auditory canal contains both sebaceous and ceruminous glands, which are modified apocrine glands. Albeit rare, benign and malignant tumors can occur in the ceruminous gland. Benign ceruminous gland neoplasms can contain ceruminous adenoma, pleomorphic adenoma, and syringocystadenoma papilliferum. Malignant ceruminous gland tumors were found to represent 0.00025 % of all neoplastic lesions in one series, and 2.4 % of all ear neoplasms, and contain adenocarcinoma not otherwise specified, adenoid cystic carcinoma, and mucoepidermoid carcinoma. Mucinous carcinoma can occur in various organs, including the gastrointestinal tract and breast, as well as the skin and salivary gland albeit rare. Herein, we report the first documented case of mucinous carcinoma occurring in the ceruminous gland. A 73-year-old Japanese male without any history of malignant neoplasms presented with a gradually enlarged tumor in his left external auditory canal. Physical examination revealed that a soft sessile tumor with hemorrhagic tendency was present in the posterior wall of the left external auditory canal. Laboratory test showed a slight elevation of serum carcinoembryonic antigen (6.2 mg/ml (range < 6.0)), but the CA19–9 levelwaswithinnormal range (16.1U/mL (range< 37.0)). Biopsy of the tumor revealed mucinous carcinoma. Computed tomography and magnetic resonance imaging revealed no tumorous lesions other than the one in the left external auditory canal, and gastroduodenal endoscopic and colonoscopic examinations also failed to demonstrate presence of other tumorous lesions. Subsequently, resection of the external auditory canal tumor was performed. The post-operative course was uneventful, and the patient has been free from tumor recurrence and metastasis during four months of medical follow-up. Microscopic examination of the resected tumor demonstrated a relatively well-circumscribed nodular lesion within the ceruminous gland (Fig. 1a). Clusters of relatively uniform neoplastic cells with slightly enlarged round nuclei containing small nucleoli and eosinophilic cytoplasm were observed within rich mucinous material (Fig. 1a,b). No mitotic figures were present. The tumor had invaded into the surrounding cartilage, although lymphovascular invasion was not observed. No conventional adenocarcinoma component was present. The ceruminous glands surrounding the tumor were hyperplastic and dilated, however, no nuclear atypia was observed (Fig. 1a). The neoplastic cells were diffusely positive for cytokeratin 7, but negative for cytokeratin 20 (Table S1). Gross cystic disease

Immunoglobulin G4-related inflammatory aortic aneurysm

1.1 The concept of immunoglobulin G4-related sclerosing disease Immunoglobulin G4 (IgG4) is the rarest subclass of IgG, which is numbered 1 through 4 in the order of their discovery and serum concentration, and normally constitutes only 3 to 6% of the total IgG fraction (Oxelius, 2008). IgG4 antibody has unique structural and functional properties, and the production of IgG4 appears to be driven in part by T helper 2 (Th2) cytokines that mediate allergic responses and IgE production (Nirula et al., 2011). The presence of IgG4 autoantibody in bullous skin diseases and high serum IgG4 concentration in patients with atopic dermatitis, bronchial asthma and bullous skin diseases have indicated that IgG4 plays an important role in these diseases (Jones et al., 1988; Jarvis et al., 2007). However, little attention had been paid to IgG4, before Hamano et al. revealed that serum IgG4 concentration was markedly elevated in patients with sclerosing pancreatitis (also called autoimmune pancreatitis) in 2001 (Hamano et al., 2001). Moreover, the same group also reported that the lesions of sclerosing pancreatitis and retroperitoneal fibrosis had abundant infiltration of IgG4-positive plasma cells (Hamano et al., 2002). Since then, many extrapancreatic lesions that share the same histopathological and immunohistochemical features as autoimmune pancreatitis have been reported in various organs, and the distinct clinicopathological disease entity, termed “IgG4-related sclerosing disease”, was established, because irrespective of origin of the organ, these lesions show common clinicopathological features (Kamisawa & Okamoto, 2008; Cheuk & Chan, 2010).

Case Report: Resection for Primary Retroperitoneal Serous Adenocarcinoma and Liver Metastasis

Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignancy of which only seven cases have been reported in the literature. The clinical features and outcomes of PRSA are not well understood. We herein report a case of PRSA with liver metastasis in a 74-year-old woman who was treated with surgical excision. The tumor cells were positive for estrogen receptor, Wilms tumor 1, PAX8, p53, and cytokeratin AE1/AE3. The final diagnosis was PRSA and liver metastasis. The pathological features of PRSA resemble those of ovarian serous carcinoma, which suggests that a combination of surgical excision with adjuvant chemotherapy may be the best option.

Tubular adenomas with clear cell change in the colorectum: A case with four lesions and a review of the literature

To the Editor: Clear cell change, defined by the presence of clear and/or vacuolated cytoplasm without obvious mucin, occurring in colorectal neoplasms has extremely rarely been reported, although various types of metaplasia or differentiation, including squamous morules and Paneth cell proliferation have been documented in colorectal tumors. One series reported a prevalence of clear cell change in colorectal adenomas of 0.086% (3/3486 cases); only 18 cases have been reported in the English-language literature. In this case report, we describe an additional case with multiple colorectal tubular adenomas showing clear cell change, and also discuss the possible pathogenesis of this phenomenon in colorectal adenomas. A 63-year-old Japanese male with a past history of prostatectomy for prostate cancer (Gleason score 3þ 41⁄47, pT2c) 1 year earlier, underwent a colorectal endoscopic examination to investigate a positive fecal occult blood test. He was found to have 25 polyps (2 in the cecum, 9 in the ascending colon, 5 in the transverse colon, 1 in the descending colon, 5 in the sigmoid colon, and 3 in the rectum). Polypectomy was performed for all the lesions. Microscopic examination of two of the polyps in the ascending colon revealed that approximately 50% of one polyp and 10% of the other polyp showed clear cell change, and the remaining portion of each represented a typical tubular adenoma with high-grade atypia (dysplasia) (Fig. 1a). Clear cell change was characterized histopathologically by the presence of clear cytoplasm in tall columnar neoplastic cells. These neoplastic cells had hyperchromatic elongated nuclei without conspicuous nucleoli. Most of the neoplastic cells had clear cytoplasm in both the apical and subnuclear portions of the cell with apically oriented nuclei (Fig. 1b,c); but in some neoplastic cells, the clear cytoplasm was present only in the apical portion with the nuclei located in the base of the cells. These neoplastic cells had clear multi-vacuolated cytoplasm, and the sizes of the vacuoles varied (Fig. 1b,c). Abrupt transition from typical tubular adenoma cells to the clear cells was observed in both polyps (Fig. 1a–c). No adenocarcinomatous component was noted in either polyp. One polyp in the descending colon and one rectal polyp appeared to be typical tubular adenomas with low-grade atypia (dysplasia) showing clear cell change (approximately 10% of cells). Periodic acid-Schiff (PAS) staining with or without diastase digestion demonstrated that most of the neoplastic clear cells did not have material that was stained by PAS, whereas the typical tubular adenoma cells contained substance that were stained by PAS and digested by diastase. Moreover, none of the clear cells contained material that was stained by alcian blue. The results of the immunohistochemical studies are summarized in Table S1 (the polyp from the descending colon was too small to be evaluated). The clear cells were negative for MUC2 expression, although MUC2 was expressed in the conventional tubular adenoma cells (Fig. 1d). MUC5AC and MUC6 were not expressed in either the clear cells or the conventional adenoma cells. CD10 was expressed in the neoplastic clear cells of all polyps (Fig. 1e). In the conventional tubular adenoma component, CD10 was expressed in one polyp in the ascending colon, but not expressed in the two other polyps. Most of the neoplastic clear cells in the three polyps showed positive immunoreactivity for adipophilin (Fig. 1f), although none of the conventional tubular adenoma cells in the three polyps were positive for adipophilin. Ki-67 labeling index (LI) was 35% and 50% (high-grade dysplasia), and 33% (low-grade dysplasia) in the clear cell components (45%, 62%, and 53% in the conventional adenoma components, respectively). Scattered p53-positive cells were observed in both the neoplastic clear cells and conventional tubular adenoma cells in all polyps. Neither SALL4 nor alpha-fetoprotein was expressed in the clear cells. The remaining 12 polyps were conventional tubular adenomas without clear cell change. Moreover, five polyps (1 in the cecum, 2 in the ascending colon, and 2 in the transverse colon) were sessile serrated adenomas/polyps, and four polyps (2 in the ascending colon, 1 in the transverse colon, and 1 in the sigmoid colon) were hyperplastic polyps. In this report, we described a case with four colorectal tubular adenomas showing clear cell change. Table S1 summarizes the clinicopathological features of the previously reported cases of colorectal adenoma with clear cell change as well as the present one (24 lesions from 20 patients, including the recently reported Japanese case). This extremely rare phenomenon is most commonly observed in the left-side colon (13/20 lesions), and rare in the ascending colon (3 lesions). Most of the patients had a single lesion; only one previously reported case had two lesions. The present case was unique, because clear cell

Presence of cancer cells in the periarterial tissues of patients with advanced gastric cancer

Lymphadenectomy with gastrectomy is considered a curative surgical treatment for gastric cancer. Periarterial connective tissue-preserving lymphadenectomy has become a common procedure following developments in laparoscopic surgery. However, the presence of cancer cells in the periarterial tissue, including neural invasion, has not been examined. In the present study, the periarterial tissues from the vessel roots of the left gastric artery (LGA) and right gastroepiploic artery (RGEA) after gastrectomy were evaluated for the presence of cancer cells. The study included 28 consecutive patients who underwent gastrectomy for gastric cancer. The vessel roots of the RGEA and LGA were obtained from surgically resected specimens and examined by two independent pathologists to determine the presence of cancer cells in the periarterial tissues. The collected specimens included 23 RGEA roots and 26 LGA roots from 28 patients. In 8 cases of early gastric cancer, no cancer cells were indicated in the periarterial tissues. By contrast, cancer cells, including neural invasion in 2 cases, were identified in the periarterial tissues from the roots of examined gastric arteries in 3/20 (15%) cases of advanced gastric cancer. Notably, all 3 cases featured multiple regional lymph node (LN) metastases. Cancer cells were detected in the perivascular tissue of the major gastric arteries from cases with advanced gastric cancer with LN metastases, suggesting the requirement for oncologic evaluation to ensure adequate vascular tissue margins and an adequate periarterial layer during lymphadenectomy.

Cytological characteristics of meningeal solitary fibrous tumor metastatic to the lung: A case report with immunocytochemical analysis

Solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal tumor, and its occurrence in the meninges is rare. We herein report what is, to the best of our knowledge, the first cytological case of meningeal SFT metastatic to the lung with immunocytochemical analysis for signal transducer and activator of transcription 6 (STAT6), and compare the cytological characteristics to those of pleuropulmonary SFT. A 58-year-old Japanese male patient was found to have multiple nodules in the bilateral lungs after surgery for meningeal SFT. Partial resection of the nodules was performed, and touch smears were obtained. The Papanicolaou smear revealed cohesive hypercellular clusters of polygonal to elongated neoplastic cells with scant cytoplasm and oval to short spindle-shaped nuclei with nucleoli containing coarse chromatin. Mild-to-moderate nuclear pleomorphism was observed. No collagenous stroma was noted. Immunocytochemical analysis revealed that the neoplastic cells diffusely expressed STAT6. Histopathological and immunohistochemical studies confirmed the diagnosis of meningeal SFT metastatic to the lung. Moreover, reverse transcription-polymerase chain reaction analysis revealed that the lung tumor harbored NAB2ex6-STAT6ex16 fusion. Recent studies demonstrated that there is a clinicopathological difference among NAB2-STAT6 fusion variants in SFT. As reflected in fusion variants, meningeal SFT occasionally lacks collagenous stroma, as in the present case, although the most characteristic cytological feature of SFT is the presence of spindle-shaped neoplastic cells embedded in dense collagenous stroma. Thus, immunocytochemical analysis for STAT6 is very useful for diagnosing SFT.

Metastatic salivary duct carcinoma in cardiac and pleural effusions: A case report with immunocytochemical analysis for androgen receptor and HER2

Salivary duct carcinoma (SDC) is a relatively rare highly aggressive salivary gland tumor. Although SDC shows frequent lymph node and distant metastases, the presence of neoplastic cells in the pleural effusion is extremely rare. In this report, we describe the first documented cytological case of metastatic SDC in cardiac and pleural effusions with immunocytochemical analyses for androgen receptor (AR) and human epidermal growth factor receptor (HER)2. A 52-year-old Japanese male developed cardiac tamponade and respiratory discomfort after surgery and chemo-radiation therapy for SDC of the right submandibular gland. Aspiration of the cardiac and pleural effusions was performed. The Papanicolaou-stained cytological specimens of cardiac and pleural effusions showed that numerous small ball-like or papillary structures were present in an inflammatory background. The neoplastic cells had rich granular cytoplasm and large round to oval nuclei containing conspicuous nucleoli. Immunocytochemical analyses clearly demonstrated positivity for AR and strong membranous expression of HER2 in the neoplastic cells. Accordingly, a cytodiagnosis of metastatic SDC was made. Recently, HER2-targeted or AR deprivation therapy have been introduced for patients with SDC, therefore, determination of expression profiles of AR and HER2 may be crucial for developing a treatment strategy for patients with metastatic SDC. According to the results of the present report, immunocytochemical analyses for AR and HER2 in the effusion specimens may be useful for determination of a treatment strategy for patients with metastatic SDC.

Thymic enteric type adenocarcinoma: A case report with cytological features

Primary thymic adenocarcinoma is an extremely rare tumor, and thymic enteric type adenocarcinoma has recently been proposed as a distinct pathological entity. Herein, we report the first cytological description of thymic enteric type adenocarcinoma. A 29‐year‐old Japanese female without a significant past medical history was found to have an abnormal chest shadow. Chest computed tomography demonstrated a well‐circumscribed tumor in the anterior mediastinum, and thymectomy was performed. The Papanicolaou staining of the touch smear of the resected tumor demonstrated tightly cohesive epithelial cell clusters in a necrotic background. These cells were cuboidal to columnar in shape and had large round to oval nuclei with conspicuous nucleoli. Some of these neoplastic cells had intracytoplasmic mucin. Immunocytochemically, the neoplastic cells were positive for cytokeratin 20 and CDX‐2. Histopathological study revealed tubular and papillotubular neoplastic growth composed of cuboidal to columnar neoplastic cells that contained large round to oval nuclei. Some of the neoplastic cells had intracytoplasmic mucin. Immunohistochemical study confirmed the expression of cytokeratin 20 and CDX‐2. The final diagnosis of thymic enteric type adenocarcinoma was made. The cytological and immunocytochemical features of this case led to a diagnosis of enteric type adenocarcinoma. However, these features alone cannot be differentiated from a metastatic adenocarcinoma arising from the gastrointestinal tract. Cytological examination of a fine‐needle aspiration of the mediastinal tumor has been reported to be useful in making a diagnosis. Therefore, an awareness of this new pathological entity is important for differentiating a thymic tumor from a metastatic carcinoma in the thymus.

Adenocarcinoma in situ admixed with small cell neuroendocrine carcinoma of the cervix: A case report with cytological features

Primary cervical small cell neuroendocrine carcinoma (SCNEC) is a rare and aggressive tumor. Herein, we describe the first cytological case of adenocarcinoma in situ (AIS) admixed with SCNEC. A 65‐year‐old postmenopausal Japanese female presented with abnormal genital bleeding. The Papanicolaou smear of the cervix demonstrated the presence of 2 distinct neoplastic components in an inflammatory background. One component consisted of aggregates of small round cells with a high nuclear/cytoplasmic ratio and round to oval nuclei with powdery chromatin, and inconspicuous nucleoli. Nuclear molding was characteristic. The other component consisted of irregular overlapping clusters of tall columnar cells with large round to oval nuclei containing coarse chromatin, and relatively rich cytoplasm. Accordingly, AIS admixed with SCNEC was suspected. Although the cytological features of cervical SCNEC are characteristic, the cytodiagnosis of this type of tumor may be difficult because of the rarity of the tumor. The presence of non‐neuroendocrine tumor components in cervical SCNEC is not unusual, therefore careful observation is needed not to miss SCNEC components in the diagnosis of squamous cell carcinoma and/or adenocarcinoma in cervical cytological specimens.