Recycling endosomal CD133 functions as an inhibitor of autophagy at the pericentrosomal region.

CD133 is a transmembranous protein that mainly localises to the plasma membrane in haematopoietic and neural stem cells as well as cancer stem cells. Although CD133 also localises to the cytoplasm, the mechanism of action and function of cytoplasmic CD133 currently remain unknown. We herein demonstrated that when Src family kinase activity is weak, CD133 interacts with HDAC6 and is transported to the pericentrosomal region after internalization and endosome formation via the dynein-based traffic system. Pericentrosomal CD133 is then recycled to the plasma membrane via recycling endosomes. At the pericentrosomal region, endosomal CD133 captures GABARAP, an initiator of autophagy, and inhibits GABARAP-mediated ULK1 activation and the subsequent initiation of autophagy. Furthermore, pericentrosomal CD133 suppresses cell differentiation, such as primary cilium formation and neurite outgrowth, by inhibiting autophagy. Thus, the present results provide evidence to suggest that pericentrosomal CD133 has the unique property of maintaining the undifferentiated status of cells by inhibiting autophagy.

Hodgkin-like peripheral T-cell lymphoma (PTCL) with preserved Hodgkin-like lesions at autopsy: a case report with an interesting clinical course.

The presence of the so-called Hodgkin and Reed-Sternberg (H-RS) like cells may occur in T-cell non-Hodgkin lymphoma. Reported herein is the autopsy case of Hodgkin-like peripheral T-cell lymphoma (PTCL) in a 77-year-old male with gradual submandibular lymph node enlargement. The first biopsy showed Hodgkin-like PTCL, initially misdiagnosed as classical Hodgkin lymphoma. Although he was treated with a regimen of ABVD, his disease recurred with cervical lymph node enlargement. A second biopsy showed angioimmunoblastic T-cell lymphoma (AITL) and H-RS like cells became obscure. Despite treatment with the CHOP regimen, he died. An autopsy confirmed that only Hodgkin-like lesions preserved while the AITL component had disappeared. This clinical course is very interesting in that only the Hodgkin-like lesions were systematically exacerbated and became the main cause of death. There are no reports of Hodgkin-like PTCL following AITL and finally preserved Hodgkin-like lesions in autopsy.

Nonsebaceous lymphadenoma in the parotid gland: true neoplastic or reactive? A report of two cases.

We report 2 rare cases of nonsebaceous lymphadenoma (NSL) in the parotid gland. In both cases, microscopic examination revealed central dilated duct-like structure and its surrounding many cysts in the background of the lymphoid stroma. The cysts were lined with luminal cells and abluminal cells, with the latter being predominant. Occasionally, foci of abluminal epithelial islands were observed. Immunohistochemical findings showed that these tumors had basal cell phenotypes and could support the diagnosis of NSL. The microscopic architectural pattern indicated a cystic dilated duct-glands unit and metaplasia or hyperplasia of abluminal cells. We wondered whether these NSLs were true neoplasia or an indication of a nonneoplastic reactive process. Further investigation of molecular studies of large series in, for example, the clonal or chromosomal state, would be necessary to clarify this point.

Gastric undifferentiated carcinoma with diffuse c-kit overexpression and focal neuroendocrine differentiation.

A case of gastric undifferentiated carcinoma with diffuse c-kit overexpression and focal neuroendocrine differentiation is described. A 76-year-old man presented appetite loss for 1 month. Gastric endoscopy showed an exophytic huge nodular mass with central ulceration at the gastric prepylorus. Distal gastrectomy was performed with lymph node dissection. Histology indicated anaplastic medium- to large-sized round tumor cells in discohesive sheets. Adenocarcinomatous areas forming tubular glands or with intracytoplasmic mucin on PAS and Alcian-blue staining were not found in any sections. Immunohistochemistry showed that the tumor cells were diffusely positive for cytokeratin, vimentin, c-kit and focally positive for chromogranin A and synaptophysin. We hypothesized that c-kit overexpression of this tumor was attributed to neuroendocrine differentiation.

Quantitative measurement of venous invasion of colorectal cancer with metachronous liver metastasis.

AIMS: Many studies have proven the importance of venous invasion in colorectal cancer with synchronous liver metastasis. The aim was to clarify the relationship between venous invasion and metachronous liver metastasis, which is not fully understood. METHODS AND RESULTS: A histological study of venous invasion in colorectal carcinoma was performed using a total of 156 patients, of whom 52 survived without recurrence for 5 years (Group A); 47 had metachronous liver metastasis (Group B), and 57 had synchronous liver metastasis (Group C). The number and the maximum area of venous invasion were estimated in each case per x 40 field of cancerous lesions, which were divided into intramural and extramural lesions. A high incidence and high average number of foci of venous invasion appeared in Groups B and C. The average maximum areas of extramural venous invasion were much larger in Groups B and C than in Group A. CONCLUSIONS: The average number of foci of venous invasion by colorectal cancer with metachronous liver metastasis did not differ significantly from that with synchronous ones. Furthermore, invasion into extramural large veins appeared to be associated with liver metastasis.

Lateral peritumoral lymphatic vessel invasion can predict lymph node metastasis in esophageal squamous cell carcinoma.

Lymph node metastasis is an important prognostic factor in many types of cancer. We investigated the clinical significance of lymphangiogenesis and lymphatic vessel invasion in esophageal squamous cell carcinoma. We evaluated lymphatic vessel density and lymphatic vessel invasion in the intratumoral, peritumoral and normal compartments using D2-40 immunostaining. In addition, the peritumoral compartment was divided into the lateral peritumoral compartment and the non-lateral peritumoral compartment. The lymphatic vessel density was higher in the peritumoral and intratumoral compartments than in the normal compartment. However, the lymphatic vessel density did not correlate with any pathological parameters including lymph node metastasis. Intratumoral and peritumoral lymph vessels were small and collapsed while normal lymphatic vessels and lymphatic vessels with lymphatic vessel invasion were dilated and large. The presence of lymphatic vessel invasion, in the lateral peritumoral compartment but nowhere else, significantly correlated with lymph node metastasis. These results suggest that lymphangiogenesis might occur with esophageal cancer, but it does not play a direct role in lymphatic vessel invasion and lymph node metastasis. Peritumoral lymphatic vessel invasion, especially in the lateral peritumoral compartment, should imply a high probability of regional lymph node metastasis.