Yumi Mihara

Thyroid papillary carcinoma with solid sclerosing change in IgG4-related sclerosing disease

IgG4‐related sclerosing disease (IgG4‐RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4‐RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4‐RSD. Solid tumor nests were surrounded by dense IgG4‐positive plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4‐related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed, and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the best of our knowledge, this is the first documentation of a malignancy of the thyroid gland occurring in a background of IgG4‐RSD. A brief review of the literature on the relationship between IgG4 and malignancy is included.

Histological Remission during Corticosteroid Therapy of Overlapping Nonalcoholic Steatohepatitis and Autoimmune Hepatitis: Case Report and Literature Review

Concurrence of nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis (AIH) is a rare condition that is challenging to diagnosis, due to the relatively high prevalence of autoantibodies in NASH. It is also difficult to determine the most effective treatment as corticosteroids are likely to worsen NASH despite being effective in the treatment of AIH. In this case report, we present a female diagnosed with NASH-AIH overlap with accompanying diabetes mellitus, who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss. A follow-up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any NASH histology. Resolution of NASH, in conjunction with a reduction in hepatic fibrosis, might suggest that prednisolone itself does not aggravate steatohepatitis, but rather prevents disease progression. Appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for NASH-AIH overlap.

De novo papillary renal cell carcinoma in an allograft kidney: Evidence of donor origin

To the Editor: An increased incidence of primary malignancies has been recognized in transplant recipients. Renal cell carcinomas (RCC) represent 4.6% of all malignancies in renal transplant recipients, whereas RCC constitutes 2% of all cancers in the general population. According to the Cincinnati Transplant Tumor Registry, there are fewer instances of RCC that develop in the allograft kidneys (up to 10%), while nearly 90% of RCC in renal transplant recipients have been found in native kidneys. De novo RCC has been described as the opposite of pre-existing tumors before transplantation. Pathological characteristics of de novo RCC occurring in the allograft kidney have not been well described. Furthermore, genetic studies to determine the tumor origin, whether from the donor or the recipient, have been performed in only a few reported RCC cases, although it is clinically important considering the association of tumor transmission. We report a case of de novo papillary RCC developing in an allograft kidney diagnosed 13 years after renal transplantation, and which was genetically confirmed to be of donor origin. A 49-year-old Japanese male presented with end-stage renal disease secondary to chronic glomerulonephritis of unknown etiology when he was at the age of 25. The patient had no family history of renal disease. After 5 years of hemodialysis, he underwent renal transplantation at the age of 29 from a deceased donor. The donor was a 37-year-old Japanese male who died of cerebral hemorrhage. The donor had no significant medical illness in his family history or past history according to medical records. Immunosuppressive therapy was maintained with methylprednisolone, cyclosporine and mizoribine. The patient presented with an episode of chronic rejection that successfully treated by steroids 7 years after transplantation. At that point, ultrasonography showed no evidence of a solid or cystic lesion in the allograft kidney. Graft function had been stable with serum creatine level of 1.1 to 1.3 mg/dL, although the patient exhibited 30 mg/dL of proteinuria on rare occasions. However, 13 years after transplantation, ultrasonography revealed a 2.3 cm solitary cystic lesion in the lower pole of the allograft kidney. During the following 7 years, the cyst had increased in size to 4.0 cm with slight blood flow inside, which led to suspicion of malignancy. There was no other cystic lesion in the allograft kidney or native kidneys. An extensive workup ruled out any primary or metastatic lesion. The patient underwent a partial nephrectomy of the allograft kidney in 2010, 20 years after transplantation. No recurrence has been found on most recent evaluation. Graft function has resumed and the patient has maintained dialysis-free status. The contralateral kidney of this particular donor, which had been transplanted to a Japanese female and resected 12 years after transplantation due to chronic rejection, presented no solid or cystic lesion. In the resected specimen, a well-circumscribed tumor was located in the renal cortex. The tumor measured 4.0 ¥ 3.5 ¥ 3.5 cm in size. The cut surface was solid and yellowish-white with tiny hemorrhages. No necrosis was noted. Histologically, a unilocular cyst was densely filled with small cuboidal cells with scanty basophilic cytoplasm. The cuboidal cells also lined the cyst wall (Fig. 1a). The tumor cells formed papillae and tubules, arranged in a single layer on the basement membrane. The nuclei were small, uniform and had hyperchromatic chromatin with a finely granular pattern. The papillary cores frequently contained aggregates of foamy macrophages and hemosiderin laden macrophages. Kidney parenchyma around the tumor showed mild interstitial fibrosis and slight tubular atrophy. Formalin-fixed paraffinembedded tissue sections were immunohistochemically stained. The antibodies used were vimentin (DAKO, Glostrup, Denmark, monoclonal, clone V9, dilution 1:100), high molecular weight cytokeratin (DAKO, monoclonal, clone 34bE12, dilution 1:100), cytokeratin 7 (DAKO, monoclonal, clone OV-TL12/30, dilution 1:100), CD10 (DAKO, monoclonal, clone SS2/36, dilution 1:100), and alpha-methylacylcoenzyme A racemase (AMACR) (DAKO, monoclonal, clone 13H4, dilution 1:100). Prostate tissue and the allograft kidney parenchyma around the tumor were used as positive control. The tumor cells were positive for vimentin, cytokeratin 7 (Fig. 1b), CD10 and AMACR, but negative for high molecular weight cytokeratin (Fig. 1c). Pathological diagnosis was papillary RCC type 1, Fuhrman’s nuclear grade 2, and stage pT1aN0M0. Comparative microsatellite analysis was performed to detect tumor origin according to a previously described method. Recipient peripheral blood and paraffinembedded tissue from the tumor and the allograft kidney parenchyma (donor tissue) were used. In total, 15 short tandem repeat (STR) markers were compared for microsatellite analysis. All of the analyzed STR markers were detected and the predominant DNA patterns of the tumor matched those of the donor, confirming that the tumor was of donor origin (Fig. 1d). The present case provides some insights into the nature of de novo RCC developing in an allograft kidney. First, the present case of RCC was confirmed to be of donor origin by microsatellite analysis on genomic DNA. It is of clinical Pathology International 2011; 61: 694–696 doi:10.1111/j.1440-1827.2011.02714.x

Apical membrane localization of glycogen synthase kinase 3β protein in normal colon epithelium and aberrant distribution in colorectal cancer

Glycogen synthase kinase 3beta (GSK-3beta) was subsequently shown to function in a wide range of cellular processes. GSK-3beta is a multifunctional serine/threonine kinase which performs a role in several signaling pathways including Wnt signal transduction. Recently, the activity of membrane-localized GSK-3beta has been shown to be crucial for initiation of Wnt cascade. In our study, the membrane localization of GSK-3beta was found on the apical membrane of normal epithelium, where co-localized and directly bound with MUC1. In colorectal cancer, depolarized cells showed the aberrant distribution of GSK-3beta on the cellular membrane with beta-catenin nuclear accumulation. The aberrant distribution of the membrane-localized GSK-3beta may contribute to the development of colorectal cancer.

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica

A case of apoplectic lymphocytic hypophysitis complicated by polymyalgia rheumatica (PMA) is described. A 72-year-old man was admitted to our hospital due to severe headache. Two months prior to admission, the patients had exhibited recent-onset stiffness and myalgia of shoulder and pelvic girdle that was compatible with PMR. Magnetic resonance imaging revealed a mass lesion in the pituitary fossa with focal hemorrhage. Endocrinologic studies demonstrated hypopituitarism. The headache and myalgia were improving with corticosteroid treatment; however, a trans-sphenoidal surgery was performed due to visual field loss. A white-colored mass was resected, and histologic examination showed diffuse infiltration of lymphocytes and plasma cells consistent with lymphocytic hypophysitis. Post-operatively, the headache and visual field loss resolved completely. This is the first documented case of apoplectic lymphocytic hypophysitis complicating PMR, and a possible mechanism for this rare association was discussed.

Protein induced by vitamin K absence or antagonist II (PIVKA-II) producing large cell neuroendocrine carcinoma (LCNEC) of lung with multiple liver metastases: A case report

A 78‐year‐old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA‐II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC). Immunohistochemistry revealed that the tumor cells expressed not only neuroendocrine markers but also PIVKA‐II diffusely. Hepatoid differentiation was not detected. Background liver did not show any chronic liver disease. The final diagnosis was PIVKA‐II producing LCNEC of the lung with multiple liver metastases. PIVKA‐II producing tumors other than HCC are extremely rare. To our best knowledge, this is the first case report of PIVKA‐II producing neuroendocrine tumors of the lung.

Low Expression of S100P Is Associated With Poor Prognosis in Patients With Clear Cell Adenocarcinoma of the Ovary.

Objective The S100P protein stimulates cell proliferation and survival, thereby contributing to cancer progression. The purposes of this study were to evaluate S100P expression in ovarian clear cell adenocarcinoma and to determine whether S100P expression was correlated with the clinicopathological features or prognoses of patients with clear cell adenocarcinoma. Methods We examined S100P expression in 30 ovarian clear cell adenocarcinoma specimens using immunohistochemistry analysis. The Kaplan-Meier method was used for analysis of overall survival, and comparisons were made based on the log-rank test. Results Negative staining for nuclear S100P was associated with a poor prognosis as compared with that of positive staining for nuclear S100P in specimens from patients with clear cell adenocarcinoma. Conclusions These data suggested that S100P may serve as an independent prognostic factor and marker for acquired resistance to chemotherapeutic drugs in clear cell adenocarcinoma.