Naomi Yada

Human intestinal spirochetosis in Japan; its incidence, clinicopathologic features, and genotypic identification

Human intestinal spirochetosis is a common condition in Western countries, but is not well recognized in Japan. To demonstrate the incidence and clinicopathologic findings of human intestinal spirochetosis in Japan, we retrospectively investigated biopsy, and endoscopically or surgically resected specimens of the large intestine. Among a series of 2556 samples, 11 cases of human intestinal spirochetosis were detected (0.4%). Together with additional nine cases sporadically found, 20 cases of human intestinal spirochetosis were subjected to molecular detection of two strains of spirochetes (Brachyspira aalborgi and Brachyspira pilosicoli) by amplifying species-specific portion of 16S ribosomal RNA and NADH oxydase gene by polymerase chain reaction. B. aalborgi was detected in all cases examined, three of which revealed dual infection of both species. Our results suggest that human intestinal spirochetosis infection is relatively rare, and B. aalborgi is the most prevalent species in Japan. Most of human intestinal spirochetosis were asymptomatic, although symptomatic in exceptional cases. In addition, we emphasize a usefulness of immunostaining with anti-Treponema pallidum and anti-Mycobacterium bovis polyclonal antibodies for detecting the spirochetes.

Aberrant methylation in promoter regions of cyclin‐dependent kinase inhibitor genes in adenoid cystic carcinoma of the salivary gland

Adenoid cystic carcinoma (ACC) is a common malignant neoplasm of the salivary gland. The mechanism underlying ACC carcinogenesis is not fully elucidated, although data on associated genetic alterations are accumulating. Cyclin‐dependent kinase inhibitors (CKIs) act as tumor suppressors in various cancers, and aberrant methylation in the CKI gene promoter region has been linked to gene silencing and downregulation of expression. The present study investigated methylation of CKI genes, p15, p18, p19, p21, and p27, in 34 cases of ACC. We found frequent and plural methylations of these genes in most cases (68.8% in p15, 90.3% in p18, 78.8% in p19, 92.3% in p21, and 26.5% in p27). Cell cycle disruption induced by these epigenetic aberrations might be important in the tumorigenesis of ACC.

White opaque substance represents an intracytoplasmic accumulation of lipid droplets: Immunohistochemical and immunoelectron microscopic investigation of 26 cases

White opaque substance (WOS) in gastric neoplasias is a unique finding visualized in magnifying endoscopy (ME) with narrow band imaging (NBI) and it represents intramucosal accumulation of lipid droplets using oil red O staining.

Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of β-catenin

BACKGROUND To clarify the genetic background of ameloblastoma, expression of beta-catenin, and mutational status of genes involved in Wnt signaling pathway were investigated. METHODS We analyzed beta-catenin and cyclin D1 in 18 cases of ameloblastoma by immunohistochemical staining, and searched for mutations in CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2 by polymerase chain reaction (PCR) and direct sequencing method. RESULT We detected membranous and occasionally cytoplasmic expression of beta-catenin in 16 of 18 cases (89%), and nuclear expression of beta-catenin principally in the peripheral columnar cells in 11 of 18 cases (61%). In nine of the 18 cases (50%), we detected the expression of cyclin D1 principally in the peripheral columnar cells. However, there was no correlation between nuclear expressions of beta-catenin and cyclin D1. No missense mutations were found in CTNNB1, APC, AXIN1, and AXIN2 in all cases except for silent mutation and already-known single nucleotide polymorphism. CONCLUSION Mutations in CTNNB1, APC, AXIN1, and AXIN2 are not implicated in nuclear accumulation of beta-catenin, and that the expression of cyclin D1 is accelerated independently of beta-catenin in ameloblastomas. Other Wnt signaling members or alternative pathways involved in the degradation of beta-catenin should be subject of further investigation.

Merkel cell carcinoma co-existent with sebaceous carcinoma of the eyelid

Merkel cell carcinoma is occasionally associated with other types of cutaneous malignancies including squamous cell carcinoma, basal cell carcinoma and lentigo maligna. We report a case of Merkel cell carcinoma co‐existent with sebaceous carcinoma in the right upper eyelid of a 61‐year‐old Japanese man. Histopathologically, the resected tumor consisted of three nodules located in the tarsal plate, showing two distinct histopathological types. Two nodules were Merkel cell carcinoma and located in the proximal part of the palpebral conjunctiva. The third was sebaceous carcinoma located in the distal transitional zone between the epidermis and the conjunctiva. No features of transition between these two components were noted. Metastatic deposits were identified in the regional lymph nodes, which solely consisted of Merkel cell carcinoma without sebaceous carcinoma. This is the first report of such co‐existent lesions.

Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature

Tanahashi J, Kashima K, Daa T, Yada N, Tanaka K‐I, Kawano Y, Yokoyama S. Pulmonary myoepithelial carcinoma resembling matrix‐producing carcinoma of the breast: case report and review of the literature. APMIS 2010; 118: 401–6.

A Case of Sebaceoma With Extensive Apocrine Differentiation

Apocrine differentiation is a rare event in sebaceoma, and only 3 cases have been reported. We report a case of sebaceoma with extensive apocrine differentiation on the scalp in a 73-year-old Japanese woman. The resected tumor was located entirely within the dermis and subcutis as a well-circumscribed, lobulated, solid, and partially cystic mass, measuring 35 mm at the largest diameter. Histopathologically, it was composed of uniform basaloid cells with clusters of sebocytes, squamous islands of ductal structures, and apocrine cells with apparent decapitation secretion. Nuclear atypia of all types of cells was inconspicuous, and mitotic figures were infrequent. We considered the lesion to be a sebaceoma with apocrine differentiation.

Carcinosarcoma ex recurrent pleomorphic adenoma of the submandibular gland

We report a case of carcinosarcoma ex recurrent pleomorphic adenoma in the submandibular region of a 56‐year‐old Japanese man. He presented with a 2‐year history of a rapidly growing mass in the submandibular region. He reported undergoing excision of a nodule in the same region 10 years earlier. Incisional biopsy confirmed the diagnosis of pleomorphic adenoma. The lesion was excised surgically. The resected tumor measured 40×20 mm and was composed of two large nodules and multiple small satellite nodules in the subcutaneous tissue. Histopathologically, one large nodule was carcinosarcoma while the other large nodules and small satellite nodules were pleomorphic adenoma. The former large nodule showed a variegated pattern with carcinomatous components (poorly differentiated adenocarcinoma, salivary duct carcinoma, squamous cell carcinoma and undifferentiated carcinoma) and sarcomatous components (spindle cell sarcoma, chondrosarcoma, liposarcoma and rhabdomyosarcoma). Based on the clinical history and histopathology, we consider the lesion to have originated from recurrent pleomorphic adenoma.

Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma.

Ren XL, Daa T, Yada N, Kashima K, Fujitomi Y, Yokoyama S. Expression and mutational status of RON in neoplastic lesions of the breast: analysis of MSP/RON signaling in ductal carcinoma in situ and invasive ductal carcinoma. APMIS 2012; 120: 358–67.

PLAG1 and CYLD do not play a role in the tumorigenesis of adenoid cystic carcinoma.

The pleiomorphic adenoma gene 1 (PLAG1) gene is activated in a subset of pleomorphic adenomas of the salivary gland by gene fusion. Germ‑line mutation in cylindromatosis (CYLD), a tumor suppressor gene, causes familial cylindromatosis and Brook‑Spiegler syndrome. In the present study, aberrations in PLAG1 and CYLD were investigated in adenoid cystic carcinoma (ACC) of the salivary gland. Reverse‑transcription PCR and PCR direct sequencing were performed to detect gene fusion of PLAG1 and mutation of CYLD in 34 ACC tissues. No PLAG1 fusion was detected in ACC. However, silent mutation of CYLD was detected in 2 cases of ACC, but no missense mutation was detected in ACC. These results suggest that PLAG1 and CYLD do not play a role in ACC tumorigenesis.