High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary EOCs, and an expression subtype (Cyto^High/Nuc^Low), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto^High/Nuc^Low subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.     

Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.     

Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

Laparoscopic grasper for intramedullary biopsy: a technique to improve tissue sampling

Reaming samples are usually sent for histological testing to establish or confirm the primary source of malignancy while intramedullary nailing is performed for impending or established pathological fracture of the long bones. However, this conventional technique of sampling does not always yield accurate results. Herein, we introduce a technique for intramedullary biopsy using a laparoscopic grasper under image intensifier guidance. This novel technique was applied in three cases, and the tissue samples obtained successfully established or confirmed the primary source of malignancy. In comparison, reaming samples obtained via the conventional method showed negative findings in one case and tumour cells that were of poor sample quality in another case. We opine that this new technique is an effective and reproducible method that could improve tissue sampling and achieve a more reliable histological diagnosis.     

Case of toxic epidermal necrolysis occurring after bone marrow transplantation accompanied by engraftment failure

Toxic epidermal necrolysis (TEN) is a rare condition, causing life‐threatening adverse cutaneous reactions. TEN occurrence after bone marrow transplantation (BMT) is a well‐known phenomenon; however, to date, only a few cases have been reported in the published work. Here, we describe the case of a 53‐year‐old woman who experienced TEN after undergoing allogenic BMT for malignant lymphoma. Skin erosion spread across a maximum of 70% of the body surface area and severe mucosal lesions developed. Steroid pulse therapy, plasma apheresis and immunoglobulin therapy were administrated, which resulted in the complete resolution of TEN. However, she developed hemophagocytic lymphohistiocytosis and died 38 days after BMT, owing to rupture of the lower digestive tract complicated by multi‐organ failure. In our case, engraftment failure occurred, and the peripheral white blood cell count was less than 100/μL during the TEN course, suggesting that the presence of only a few immune cells could cause TEN. Our findings showed that high mortality rates and widespread skin erosion could be regarded as the most important characteristics of TEN occurring after BMT.