Chika Miyasaka

Utility of immunohistochemical analysis of KAI1, epithelial-specific antigen, and epithelial-related antigen for distinction of chromophobe renal cell carcinoma, an eosinophilic variant from renal oncocytoma.

Distinction of renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) is important because their clinical behavior is different. As part of a search for the best available immunohistochemical markers to distinguish ChRCC from RO, we investigated the immunohistochemical profiles of these tumors. We selected 30 renal tumors consisting of ChRCC, typical variant (n = 14), ChRCC, eosinophilic variant (n = 6), and RO (n = 10). Their expression of cytokeratin (CK) 7, KAI1, epithelial-specific antigen (ESA), epithelial-related antigen (ERA), Claudin- 7, and Claudin-8 was studied using an autostainer. Immunoreactivity was assessed based on a combined score of the extent and intensity of staining. Compared to RO, a significantly higher percentage of the total ChRCCs stained positive for CK7 (85% vs. 10%, respectively), KAI1 (90% vs. 10%), ESA (95% vs. 10%), ERA (95% vs. 10%), and Claudin-7 (95% vs. 20%) (P < 0.001). Additionally, there was a significant difference between the percentage of ChRCC eosinophilic variant (ChRCC-E) and RO that stained positive for KAI1 (100% vs. 10%, respectively), ESA (83% vs. 10%), and ERA (83% vs. 10%) (P < 0.001). We recommend immunohistochemical analysis of KAI1, ESA, and ERA to distinguish ChRCC-E from RO.

IgG4-related Disease Involving Multiple Organs with Elevated Serum Interleukin-6 Levels.

A 63-year-old woman presented to our hospital with elevated levels of serum IgG4, marked wall thickening of the gallbladder, hepatomegaly, and abdominal lymphadenopathy. She experienced a recurrent fever and leg edema. Her laboratory data demonstrated anemia, hypoalbuminemia, and elevated serum levels of interleukin-6 and C-reactive protein. The patient was eventually diagnosed with IgG4-related disease according to the comprehensive diagnostic criteria, although the patient exhibited common clinical manifestations of multicentric Castleman disease such as a fever, anemia, lymphadenopathy, and elevated levels of serum interleukin-6 and C-reactive protein. This case report highlights the difficulties in differentiating between these two diseases.

Clinicopathologic Diversity of Undifferentiated Sarcoma With : Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3 bcor-ccnb3 : Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3 Fusion: Analysis of 11 Cases With a Reappraisal of the Utility of Immunohistochemistry for Bcor and Ccnb3

Undifferentiated sarcoma harboring the BCOR-CCNB3 fusion is characterized by its predilection to affect skeletons of adolescent males, cellular small round/spindle cell morphology, and CCNB3 immunoreactivity. We analyzed 11 cases of BCOR-CCNB3 sarcoma, 10 of which were identified in a reverse transcription-polymerase chain reaction–based screen of 85 patient samples recorded in our database as unclassified small round or spindle cell sarcomas. BCOR rearrangements were confirmed by fluorescence in situ hybridization in 8 tumors. All patients were males aged between 6 and 31 years. In addition to 5 tumors in soft tissue and 4 in the axial or appendicular skeletons, which are typical locations, a tumor was located in the paranasal sinus and another in the lung. Microscopically, the tumors comprised proliferating atypical spindle and/or small round cells with diverse morphologic features such as small concentric whorls, myxoid stroma, a hemangiopericytomatous appearance, and/or hyalinized collagen resembling a solitary fibrous tumor, and angiomatous or slit-like spaces containing extravasated erythrocytes. Tumor cells were immunoreactive to CCNB3 (9/11), BCOR (10/10), TLE1 (6/10), bcl-2 (9/11), CD99 (8/10), CD56 (8/10), c-kit (4/10), and cyclin D1 (10/10). In an immunohistochemical analysis of an additional 412 small round or spindle cell tumors, CCNB3 was detected in 6 (1.5%) and BCOR in 18 (4.4%). Our analysis highlights the varying clinicopathologic features of this tumor, which partially overlap with other small round or spindle cell tumors, including solitary fibrous tumor and vascular tumors. Because CCNB3 and BCOR immunohistochemistry lacks adequate sensitivity and specificity, a molecular genetic approach remains essential for diagnosis.

Novel strategy for cystitis glandularis: Oral treatment with cyclooxygenase-2 inhibitor

Cystitis glandularis, a proliferative disease of the bladder, is resistant to antibiotics, non‐steroidal anti‐inflammatory drugs, anti‐allergy drugs and transurethral resection. Cystectomy or partial cystectomy is occasionally required for refractory cystitis glandularis. It has not been defined if cystitis glandularis is a premalignant lesion. We experienced a case of remission from cystitis glandularis after combination of oral treatment with selective cyclooxygenase‐2 inhibitor, celecoxib and transurethral resection. Immunohistochemistry showed positive signals of cyclooxygenase‐2 in the epithelium of pretreatment specimens, suggesting the pathophysiological role of cyclooxygenase‐2 in cystitis glandularis. Here, we show the effectiveness of celecoxib against cystitis glandularis for the first time. Celecoxib could be one of the therapeutic strategies for cystitis glandularis.

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

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.

Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes

Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing morphological and immunohistochemical resemblance of hepatocellular carcinoma. The occurrence of this type of tumor in the gallbladder is extremely rare. In this study, we report the first cytological case of hepatoid adenocarcinoma of the gallbladder. An 80‐year‐old Japanese female was found to have a tumorous lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few epithelial cell clusters composed of round to oval neoplastic cells with distinct cell border and large centrally‐located nuclei. Tumor touch smear of the resected tumor revealed the presence of two distinct neoplastic components. The first component was composed of clusters or sheets of epithelial cells with distinct cell border, relatively rich clear cytoplasm, and centrally‐located nuclei, as seen in the ascites specimen. The other component was composed of tall columnar cells with large basally‐oriented nuclei, and glandular formation was noted as well. Immunocytochemical analyzes of the touch smear material demonstrated that the former component was positive for HepPar1, thus it was considered as a hepatoid adenocarcinoma, and the latter component deemed as a typical adenocarcinoma. Histopathological and immunohistochemical examination of the resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The characteristic cytological features of hepatoid adenocarcinoma are the presence of sheets or clusters of neoplastic cells with distinct cell border and centrally‐located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis. Demonstration of hepatoid adenocarcinoma is important in the cytological specimen because this type of tumor shows an aggressive clinical course.

Esophageal Large-Cell Neuroendocrine Carcinoma with Inconsistent Response to Treatment in the Primary and Metastatic Lesions

Esophageal large-cell neuroendocrine carcinoma (NEC) is a rare malignant tumor that is characterized by high-grade malignancy and a poor prognosis. However, the rarity of esophageal NEC has prevented the development of an established treatment, and no reports have described a discrepancy in the effectiveness of cisplatin plus irinotecan between primary and metastatic lesions. A 43-year-old Japanese man was referred to our hospital with refractory epigastralgia. A previous gastrointestinal endoscopy had revealed a 50-mm type 2 tumor in the abdominal esophagus. The pathological findings indicated poorly differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a metastatic liver tumor. One cycle of fluorouracil and cisplatin was not effective, and endoscopy was repeatedly performed. The pathological findings indicated a large-cell malignant tumor with tumor cells that were positive for CD56, synaptophysin, and Ki-67 (> 80%). Based on a diagnosis of esophageal large-cell NEC with a metastatic liver tumor, the patient received cisplatin plus irinotecan biweekly. After 4 months, computed tomography revealed marked shrinkage of the metastatic tumor, but the patient complained of dysphagia. Endoscopy revealed enlargement of the primary tumor, which was then treated using radiotherapy plus fluorouracil and cisplatin. The primary tumor subsequently shrank, and the patient’s symptoms were relieved, but the metastatic tumor grew. Thus, chemoradiotherapy could be an option for managing a primary esophageal large-cell NEC that does not respond to chemotherapy alone. However, the possibility of an inconsistent response to therapy in primary and metastatic lesions should be considered.

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.

The role of CD5 expression in thymic carcinoma: possible mechanism for interaction with CD5+ lymphoid stroma (microenvironment)

Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self‐reactive CD5 antigen in thymic carcinoma.