Epithelial Mucinosis in Exophytic Endobronchial Squamous Cell Carcinoma

Three cases of exophytic squamous cell carcinoma of the lung in which an unusual epithelial change with intercellular mucin deposit; namely epithelial mucinosis, was present in variable degree are reported here. As either exophytic variant of lung carcinomas or its mucinotic change is rare, the general concept of this lung carcinomas is summarized and the significance of epithelial mucinosis is discussed

Intraluminal Polypoid Fibrosis of the Lung

The present communication describes the morphology and pathogenesis of intraluminal (or intra-alveolar) polypoid fibrosis of the lungs, which is a condition characterized histologically by the presence of polypoid fibrous tissue masses protruding into and filling lumens of the airways or airspaces. Intraluminal polypoid fibrosis is further subclassified into three types. The first type probably represents a primary injury of respiratory bronchioles and alveolar duct walls which directly leads to polypoid fibrous tissue formation. This fibrous tissue is generally uniform in appearance and lacks a fibrinous component. The second type results from fibrous replacement of preceding fibrinous inflammation in the airspaces, such as lobular (broncho-) and lobar pneumonia. It is histo logically characterized by an admixture of fibrin and fibrous components. The third type superimposes on hyaline membrane formation. The spaces surrounded by the hyaline membrane along the alveolar duct walls are filled with loose fibrous tissue. In all three types, the process of organi zation originates in the alveolar duct walls, especially at the edge of alveolar mouths. Therefore, we propose the term of "fibrosing alveolar ductitis syndrome" for such disease entities as BOOP, BIP, and organized DAD. in which damage of the alveolar duct wall results in fibrosis

Traumatic Neuroma of the Gallbladder : Report of a Case

A case of traumatic neuroma of the gallbladder is reported. Most of traumatic neuromas of the biliary system arise at the cystic duct stump after cholecystectomy. Review of the English literature disclosed only one case of traumatic neuroma of the gallbladder. The reported case had a history of unsuccessful cholecystectomy performed twenty years previously. In our case, in contrast, traumatic neuroma developed without a history of previous operation. Prolonged presence of cholecystoduodenal fistula was suspected as an etiological factor

Glandular Inclusion in the Periprostatic Nerve Ganglion

The presence of epithelial cells in the nerve tissue is generally regarded as indicative of malignant neoplasia in the prostate, although it may be encountered in the benign breast lesions. Recently, however, we have observed a normal-looking prostatic gland epithelium in the nerve ganglion near hyperplastic prostate. This case, therefore, indicates that benign epithelial-nerve intermingling may occur in the prostatic tissue and that the identification of epithelial cells within nerves as malignant should be more careful in the prostatic gland as is in the breast tissue

Androgen receptor and 5α-reductase immunohistochemical profiles in extramammary Paget disease

Background Extramammary Paget disease is an uncommon skin tumour occurring mostly in the genitoperineal region. Previous reports have shown frequent expression of androgen receptor, suggesting a tumour-proliferative effect of androgens on Paget cells. Androgen-converting enzymes such as 5α-reductase, which locally produces a bioactive androgen, have recently gained attention in studies of the intratumoral actions of androgens. Objectives We investigated correlations between the androgenic microenvironment and invasiveness in extramammary Paget disease, particularly in terms of sex differences. Methods We examined 58 cases of extramammary Paget disease (32 men, 26 women; 42 noninvasive, 16 invasive) using immunohistochemistry for androgen receptor and 5α-reductase. Results In all 58 cases, expression rates were 57% for androgen receptor and 55% for 5α-reductase, with 38% double-positivity for androgen receptor and 5α-reductase. Only 5α-reductase expression rate was significantly higher in invasive cases (81%) than in noninvasive cases (45%; P = 0·042). For invasive cases, numbers of double-positive results for androgen receptor and 5α-reductase were significantly higher in men (70%) than in women (17%; P = 0·039). Conclusions Double positivity for androgen receptor and 5α-reductase in Paget cells suggests autocrine synthesis of androgens in extramammary Paget disease. The different hormonal microenvironments in male and female cases and intratumoral androgen levels affect the invasiveness of extramammary Paget disease. © 2010 British Association of Dermatologists

Predictors for the outcomes of patients with estrogen receptor-positive, HER2-negative advanced breast cancer treated using palbociclib plus endocrine therapy

　A cyclin-dependent kinase (CDK) 4/6 inhibitor, palbociclib (PAL), combined with endocrine therapy is frequently used for the treatment of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative advanced breast cancer. However, as predictors for the outcomes remain unclear, we retrospectively investigated them.　A total of 36 patients with ER-positive, HER2-negative advanced breast cancer were treated using PAL plus endocrine therapy at our hospital. Treatment outcomes, objective response rates (ORR), progression-free survival (PFS) and post-treatment overall survival (OS) were analyzed. As possible predictive biomarkers, retinoblastoma protein (Rb), phosphorylated Rb (pRb) and different CDKs were immunohistochemically investigated using primary tumor tissues. Non-visceral metastasis, use of fulvestrant (FUL) and the 1st- or 2nd-line treatment were significant predictors for a better ORR (P = 0.0080, P = 0.0080 and P = 0.0080, respectively). No objective response (OR) was observed in patients with progesterone receptor (PR)-negative, CDK6-positive or cytosolic cyclin E1-positive tumors. Non-visceral metastasis and use of FUL were significant predictors for a better PFS (P = 0.0030 and P = 0.0443, respectively). The Cox proportional hazards model revealed that visceral metastasis (hazard ratio [HR], 4.9; P = 0.0019) and PR-negativity (HR, 3.2; P = 0.0411) were independent predictors for a poorer PFS. Nonvisceral metastasis, pRb-negativity and CDK6-negativity were significant predictors for a better OS (P = 0.0281, P = 0.0014 and P = 0.0396, respectively). The Cox proportional hazards model revealed that visceral metastasis (HR, 7.2; P = 0.0131) and pRb-positivity (HR, 18.5; P = 0.0060) were independent predictors for a poorer OS.　In conclusion, PR-negativity and pRb-positivity in primary tumors may be independent predictors for PFS and OS, respectively. CDK6-positivity and cytosolic cyclin E1-positivity may be predictors for a poorer OS and ORR, respectively. Further investigation is needed to confirm these factors

Role of the expression of collagen prolyl-4-hydroxylase α subunits 1 and 2 in the development and prognosis of breast cancer

　Background: The expression of prolyl-4-hydroxylase (P4H), an enzyme involved in collagen biosynthesis, is significantly upregulated during breast cancer development and progression. However, the molecular mechanisms by which P4H expression in cancer cells induces progression have not been elucidated. Thus, we aimed to determine the significance of the expression of isoforms 1 and 2 of P4H in breast cancer.　Methods: We performed immunohistochemical analysis for P4HA1 and P4HA2 on the tumor samples obtained from 182 patients with breast cancer and examined the correlation between clinicopathological factors and markers related to epithelial-mesenchymal transition and ischemia. Protein expression levels were investigated using western blotting. In addition, breast cancer cell cultures were used to characterize the expression.　Results: Expression of both P4HA1 and P4HA2 was upregulated in cancer cells compared with that in normal mammary glands; the high-P4H expression group tended to have a poorer prognosis than the low-P4H expression group. In particular, P4HA2 was strongly associated with tumor grade; P4HA2 expression showed a weak negative correlation with HIF-2α expression. In cultured breast cancer cells, the immunohistological expression of P4H and HIF increased tovarious degrees under hypoxia, while P4H protein levels increased in a time-dependent manner. 　Conclusion: P4HA2 can be used as a marker of breast cancer grade and a prognostic factor. Differential expression of P4HA1 and P4HA2 was observed in an ischemic environment,suggesting that each may be affected by the type of collagen involved

リポポリサッカライドの外因性投与はコリン欠乏 L-アミノ酸置換食誘発脂肪性肝炎モデルマウスにおいて肝線維化を促進する

Various rodent models have been proposed for basic research; however, the pathogenesis of human nonalcoholic steatohepatitis (NASH) is difficult to closely mimic. Lipopolysaccharide (LPS) has been reported to play a pivotal role in fibrosis development during NASH progression via activation of toll-like receptor 4 (TLR4) signaling. This study aimed to clarify the impact of low-dose LPS challenge on NASH pathological progression and to establish a novel murine NASH model. C57BL/6J mice were fed a choline-deficient l-amino-acid-defined (CDAA) diet to induce NASH, and low-dose LPS (0.5 mg/kg) was intraperitoneally injected thrice a week. CDAA-fed mice showed hepatic CD14 overexpression, and low-dose LPS challenge enhanced TLR4/NF-κB signaling activation in the liver of CDAA-fed mice. LPS challenge potentiated CDAA-diet-mediated insulin resistance, hepatic steatosis with upregulated lipogenic genes, and F4/80-positive macrophage infiltration with increased proinflammatory cytokines. It is noteworthy that LPS administration extensively boosted pericellular fibrosis with the activation of hepatic stellate cells in CDAA-fed mice. Exogenous LPS administration exacerbated pericellular fibrosis in CDAA-mediated steatohepatitis in mice. These findings suggest a key role for LPS/TLR4 signaling in NASH progression, and the authors therefore propose this as a suitable model to mimic human NASH.博士（医学）・甲第738号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Folliculotropic mycosis fungoides treated with electron beam therapy that evolved into fatal, tumor-stage mycosis fungoides and erythroderma with multiple ulcerations

　A 71-year-old woman diagnosed with mycosis fungoides with multiple erythematous plaques and follicular papules on the scalp, trunk, and thigh was referred to our institution. Folliculotropic mycosis fungoides was histologically diagnosed, and the erythematous papules and plaques regressed temporarily after total-skin electron beam therapy. The patient then developed tumors and erythroderma. The area of painful erosion spread, and her condition rapidly worsened. The patient died 3 years and 4 months after the first examination due to multiple organ failure caused by sepsis. The cause of rapid evolution into erythroderma remains elusive and requires further investigation in similar cases