A novel germline BMPR1A variant (c.72_73delGA) in a Japanese family with hereditary mixed polyposis syndrome.

Hereditary mixed polyposis syndrome (HMPS) is a rare autosomal dominant disorder characterized by a mixture of typical and/or atypical juvenile polyps, adenomas and hyperplastic polyps, resulting in an increased risk of colorectal cancer. In HMPS, four different germline BMPR1A variants from five unrelated families have been reported. This study is the first to report HMPS within a Japanese family. The proband underwent repeated colonoscopic polypectomies over a 5-year period, since the age of 67. Histological examination of these resected polyps revealed adenomas, juvenile-like polyps and hyperplastic changes. Genetic testing was conducted to identify the causative genes for hereditary gastrointestinal cancer syndromes, including BMPR1A. We detected a germline variant, c.72_73delGA, in BMPR1A. The proband's elder brother, younger sister and nephew have also undergone repeated colonoscopic polypectomies at other clinics. His sister and nephew underwent genetic testing, and the same BMPR1A variant was identified.

[A case of myasthenia gravis with transient taste disorders followed by aplastic anemia after thymectomy].

A 45-year-old man was admitted to our hospital because of taste disorders in March 2014. He exhibited cervical muscle weakness and left eye ptosis, which responded to Tensilon test, and was diagnosed with myasthenia gravis (MG). He developed aspiration pneumonia and myasthenic crisis, which was treated with intravenous immunoglobulin and steroid pulse therapy. All symptoms disappeared. Oral administration of prednisolone and tacrolimus was started. Chest CT revealed thymoma and extended thymectomy was performed in May 2014. In December 2014, seven months after the thymectomy, hematological examination showed pancytopenia including severe neutropenia. We diagnosed his illness as aplastic anemia (AA). Cyclosporine therapy with transfusion was administerd and led to reticulocyte count recovery. Since May 2015, hemoglobin recovery reached a blood transfusion free period. To our knowledge, this is the first case report with the patient supposed of relationship among taste disorders, AA and thymoma-associated MG.

Ectopic pregnancy developing in a cyst of the canal of Nuck.

BACKGROUND: A cyst of the canal of Nuck is a rare cause of inguinal swelling in adult women. Ectopic pregnancies that implant to rare regions are sometimes challenging to diagnose. CASE: A 45-year-old woman presented with painful swelling in her right groin with a positive urine pregnancy test. Ultrasonography, magnetic resonance imaging, and the histopathologic result of dilation and curettage suggested ectopic pregnancy in the right inguinal canal. Exploratory laparotomy, extraction of the right inguinal mass lesion, and closure of the deep inguinal ring were performed. The mass lesion measured 4×3 cm, and the histopathologic finding revealed an unusual ectopic pregnancy in the cyst of the canal of Nuck. CONCLUSION: In women of reproductive age presenting with painful swelling of the groin, ectopic pregnancy in a cyst of the canal of Nuck should be ruled out.

Pemphigoid gestationis after spontaneous expulsion of a massive complete hydatidiform mole.

Pemphigoid gestationis (PG) is a rare, perinatal, autoimmune, and blistering dermatosis. Only few cases of PG involving hydatidiform moles have been reported. Complete hydatidiform moles are usually evacuated by dilatation and curettage. We report a patient with a massive complete hydatidiform mole that underwent spontaneous expulsion; she subsequently developed PG. A 19-year-old unmarried nulligravid woman was referred to our hospital following excessive vaginal bleeding after an uncertain amenorrheal period. The patient presented with preshock vital signs, severe anemia, and a positive urine pregnancy test. Imaging examinations revealed a massive intrauterine mass (19 × 15 × 10 cm), suggesting a complete hydatidiform mole. She was hospitalized and treated with blood transfusion. Sixteen hours after hospitalization, the massive molar mass underwent spontaneous expulsion and bleeding ceased. Three days after the expulsion, she developed pruritic skin lesions including papules, erythemas, and bullae, which spread over her entire body. Skin biopsy revealed PG and subepidermal blister formation and linear complement C3 deposition along the basement membrane zone, and the serum anti-BP180 antibody level was found to be high on measurement. She was effectively treated with 50 mg/day of oral prednisolone. Her skin lesions disappeared, leaving pigmentation.

Malignant transformation of ovarian mature cystic teratoma with a predominant pulmonary type small cell carcinoma component.

A 68-year-old woman was diagnosed with mature cystic teratoma of the left ovary when she was 44 years old. The tumor recently enlarged rapidly, and abdominal magnetic resonance imaging revealed an intrapelvic cystic lesion, which measured 123 × 120 × 107 mm and contained a mural nodule. Under a clinical diagnosis of malignant transformation of mature cystic teratoma, bilateral salpingo-oophorectomy with total hysterectomy and omentectomy were performed. The resected specimen showed a unilocular cystic lesion containing a well-demarcated mural nodule measuring 35 × 30 × 25 mm in the left ovary. A microscopic examination revealed various types of carcinoma in the mural nodule: pulmonary type small cell carcinoma (65%), adenocarcinoma (25%), squamous cell carcinoma (5%), and transitional cell carcinoma (5%). Small cell carcinoma was positive for CD56, synaptophysin, and chromogranin A. The adenocarcinoma component showed intestinal phenotypes; i.e. cytokeratin (CK) 7(-), CK20(+), CDX2(+), estrogen receptor(-), and progesterone receptor (-). Interestingly, CDX2 positivity was retained in all of the carcinomas. It was assumed that the adenocarcinoma had arisen from an intestinal epithelium in the mature cystic teratoma and then differentiated into the diverse histological types mentioned above.

[Histological complete response in a case of advanced gastric cancer treated by neoadjuvant TS-1 combined with CDDP therapy].

A 63-year-old woman with advanced gastric cancer was referred to our hospital.Upper gastrointestinal endoscopy revealed a type 2 tumor in the lesser curvature of the angle of stomach. Moderately-differentiated adenocarcinoma was found in the biopsy specimens. Lymph node metastases of No.3 and No.7 were suspected by abdominal CT. We diagnosed the tumor as cStage III A (cT2N2H0P0M0) gastric cancer.For better curability, we selected neoadjuvant chemotherapy with TS-1/ CDDP. Two courses were completed without serious side effects. Upper gastrointestinal endoscopy and abdominal CT revealed that the primary tumor and metastatic lymph nodes had become smaller, suggesting that a partial response had been achieved. The patient underwent curative surgery, including distal gastrectomy and D2 lymph node dissection.No cancer cells were found by pathological evaluation of the resected stomach and all the regional lymph nodes, confirming a pathological complete response. It is suggested that the neoadjuvant chemotherapy is a useful therapeutic strategy for advanced gastric cancer.

Malignant pleural mesothelioma: clinicopathology of 16 extrapleural pneumonectomy patients with special reference to early stage features.

The earliest pathological events in the development of malignant pleural mesothelioma (MPM) are not understood. The aim of the present study was to elucidate the early histopathological features of MPM. A total of 16 extrapleural MPM pneumonectomy patients were investigated. Early stage mesothelioma was arbitrarily defined as a tumor < or =5 mm in thickness regardless of the nodal status or other organ involvement. Eight of these patients (six with epithelioid, two with biphasic) had early stage mesothelioma by this definition. Macroscopically there was no visible tumor, but the parietal and visceral pleura were thickened and there was focal adhesion between them. Microscopically, the mesothelioma lesions were multifocal and discontinuous on the pleura. In extremely early cases of epithelioid mesothelioma, tumor cells were generally arrayed in a single layer, but papillary proliferation was observed elsewhere. In sarcomatoid mesothelioma, mesothelioma cells proliferated, forming multiple small polypoid nodules on the pleura. Epithelial membrane antigen was helpful to distinguish reactive from neoplastic mesothelium, but glucose transporter-1 was not. Mesothelioma cells disseminate diffusely throughout the parietal and visceral pleura and mediastinal fat tissue before becoming visible. Stage Ia mesothelioma (neoplasm limited to the parietal pleura) would not be observed in daily practice.

Expression of E-cadherin, alpha-catenin, and beta-catenin in tubulolobular carcinoma of the breast.

Tubulolobular carcinoma (TLC) of the breast is a rare subtype of breast carcinoma categorized by Fisher et al. (Hum Pathol 8:679-683, 1977) as a tubular variant of lobular carcinoma. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma. Ductal carcinoma retains at least some expression of E-cadherin. Moreover, the adhesive function of E-cadherin is dependent on the integrity of the catenin components, which link E-cadherin to the actin filaments. In order to achieve improved categorization of TLC, we decided to investigate both E-cadherin and the catenins in TLCs and invasive lobular carcinomas. We reviewed all 1,430 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, and at Saitama Red Cross Hospital between 1990 and 2005. Among these, 16 cases of TLC were reported retrospectively. The results were compared with those of 20 cases of invasive lobular carcinomas that were included as controls. Tumor tissue was immunostained for E-cadherin, alpha-catenin, and beta-catenin. The presence of immunoreactivity in the TLC was seen in 12 (75%) cases for E-cadherin, in 8 (50%) cases for alpha-catenin, and in 10 (62.5%) cases for beta-catenin. However, plasma-membrane-associated staining for E-cadherin, alpha-catenin, and beta-catenin was completely absent in invasive lobular carcinomas. These results suggest the possibility that TLCs are not a variant of lobular carcinoma, but rather ductal carcinomas with a lobular growth pattern.

No evidence of a correlation between BCL10 expression and API2-MALT1 gene rearrangement in ocular adnexal MALT lymphoma.

In the present study, 62 cases of ocular adnexal lymphoproliferative disorders were reviewed clinicopathologically. Of them, 51 were extranodal marginal zone B-cell lymphoma (MALT lymphoma), five were diffuse large B-cell lymphoma (DLBCL), one was peripheral T-cell lymphoma, one was NK/T cell lymphoma, nasal type, and four were reactive lymphoid hyperplasia. These lymphoma cases showed a favorable clinical course and localized disease, except for the case of NK/T cell lymphoma, although 19 cases (32.8%) had a recurrence of disease. To clarify the correlation between BCL10 protein expression and API2-MALT1 gene rearrangement, the 51 cases of MALT lymphoma and 5 cases of DLBCL were analyzed by immunohistochemical and RT-PCR methods. Nuclear BCL10 expression was identified in 58% of MALT lymphoma cases, but not in any DLBCL cases. There was no evidence of a correlation between aberrant nuclear BCL10 expression and the clinical parameters examined in the present study. API2-MALT1 transcription was not demonstrated in either the MALT lymphoma cases or the DLBCL cases studied using a multiplex one-tube reverse transcriptase-PCR method. These findings indicate that the nuclear expression of BCL10 is unlikely to correlate with the API2-MALT1 fusion gene in ocular adnexal MALT lymphoma.

[Serious renal infection: report of three cases].

In renal infections, lack of peculiar symptoms and consequent delay of diagnosis can sometimes lead to a critical condition of the patient. We report three cases of life-threatening renal infections in female patients, two of which were subsequently fata. One patient died of left emphysematous pyelonephritis with bilateral pleuritis. The patient was correctly diagnosed 13 days after the onset of symptoms and expired 2 months later despite nephrectomy on the day of diagnosis. The second patient died of septic shock 3 days following the onset of symptoms. Autopsy revealed multiple perinephric abscess of the left kidney. The non-fatal case was a perinephric abscess spread to the iliopsoas muscle. The patient was diagnosed with perinephric abscess 11 days after the onset of symptoms and eventually underwent nephrectomy 9 days later. Two of the patients were diabetics and the third was a probable diabetic, who died too suddenly to confirm the diagnosis. Herein, we review the literature of, and discuss the diagnosis and management of serious renal infection.