Mutational analysis of Wnt signaling molecules in ameloblastoma with aberrant nuclear expression of beta-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.

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.

Multiple calcifying fibrous tumors of the pleura.

Calcifying fibrous tumor (CFT) is a rare lesion characterized histologically by hypocellular hyalinized collagenous tissue with psammomatous and/or dystrophic calcifications and patchy lymphoplasmacytic infiltrates. CFT usually occurs in the somatic soft tissue of children and young adults but is rarely found in the pleura. We describe here an unusual case of multiple small CFTs in the right mediastinal pleura of a 54-year-old man who had a history of renal cell carcinoma. Suspecting pulmonary and pleural metastases, we performed wedge resection of the right middle lobe and local excision of two nodules in the right pleura. Light microscopy revealed metastatic lesions of renal cell carcinoma in the resected wedge. The pleural nodules were well circumscribed and composed of hypocellular, dense, hyalinized, collagenous tissue with scant lymphoplasmacytic infiltration and characteristic psammoma bodies. Immunohistochemical staining revealed that most spindle cells were positive for vimentin, CD34 and factor XIIIa, and negative for epithelial membrane antigen, keratin, smooth-muscle actin, desmin, S-100 protein and anaplastic lymphoma kinase. We made a histological diagnosis of CFT of the pleura, and the patient remains well 6 months after the wedge resection.

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.

The Wnt-signaling pathway is not implicated in tumorigenesis of Merkel cell carcinoma.

BACKGROUND: The Wnt-signaling pathway, involving beta-catenin, apc, and axin, plays a critical role in numerous developmental events. Alterations in the Wnt-signaling pathway have been detected in a wide variety of neoplasms. However, similar aberrations have not been described in Merkel cell carcinoma (MCC). The aim of this study was to determine the status of the Wnt-signaling pathway in MCC. METHODS: Twelve cases of MCC were tested for the expression of beta-catenin and mutational status of CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2. Genomic DNA extracted from paraffin blocks was subjected to a polymerase chain reaction/single-strand conformation polymorphism analysis and sequencing. RESULTS: Nuclear accumulation of beta-catenin was observed in only one case (8.3%), as determined by immunochemistry. No mutations were found in CTNNB1, APC, and AXIN2 in all cases, although silent mutations in AXIN1 were detected in three cases. CONCLUSIONS: We conclude that the Wnt-signaling pathway does not play an important role in tumorigenesis in MCC.

Solitary fibrous tumor of the thyroid gland: report of two cases and review of the literature.

Presented herein are the first two Japanese cases of solitary fibrous tumor (SFT) of the thyroid gland. The patients were 64- and 41-year-old men, who underwent hemithyroidectomy for thyroid tumors. Histopathologically, the tumors were well circumscribed, and were composed of spindle cells, collagen bundles and entrapped thyroid follicles. Spindle cells and collagen bundles were mostly in a patternless arrangement with an admixture of hypo- and hypercellular areas. Proliferating spindle cells were bland, slender, and occasionally wavy without any atypia and increased mitotic figures. Immunohistochemically, they were strongly positive for CD34, CD99, and bcl-2, but negative for epithelial membrane antigen, keratin, thyroglobulin, calcitonin, thyroid transcription factor-1, alpha-smooth muscle actin, desmin, S-100 protein and CD117. Based on these findings, the two patients were diagnosed as having thyroid SFT. Neither local recurrence nor metastasis has been observed in 5 years in patient 1 or in 4 years in patient 2. Thyroid SFT is extremely rare, and only 20 cases have been reported in the English-language literature including hemangiopericytoma. Although recurrence or metastasis has not been described in any reported cases, the clinical behavior of SFT is still undetermined, therefore long-term follow up seems necessary at present.

Porocarcinoma arising in pigmented hidroacanthoma simplex.

Hidroacanthoma simplex (HAS) is a rare benign tumor that is also known as intraepidermal poroma. While there have been a few reports of HAS with malignant transformation (porocarcinoma), we report an unusual case of porocarcinoma, arising in a pigmented HAS, the latter also showing secondary amyloid deposits. An 80-year-old Japanese man presented with a cutaneous tumor on his left buttock, which had first been noticed in his childhood. The tumor consisted of flat pigmented plaque and a depigmented papule with erosion. Histologic analysis revealed many pigmented and well-defined nests within the epidermis of the flat pigmented portion. The nests were composed of cuboidal to oval and occasionally elongated, bland, basaloid cells with numerous melanin granules. In addition, there were infrequently ductal structures and small clusters of sebocytes, and abundant amyloid deposits in the upper dermis. These findings were consistent with pigmented HAS with amyloid deposition. In the depigmented portion, markedly atypical cells with occasional ductal structures and intracytoplasmic lumina extended throughout the entire thickness of the epidermis, with minimal invasion of the dermis. We considered this portion of the tumor to be a porocarcinoma. Since the two portions of the tumor were continuous, we made a final diagnosis of porocarcinoma arising in pre-existing pigmented HAS with amyloid deposition.