Successful Surgical Treatment of a Recurrent Pelvic Solitary Fibrous Tumor of Uterine Origin Accompanied by Doege-Potter Syndrome: A Case Report.

BACKGROUND Solitary fibrous tumors (SFT), rare soft-tissue neoplasms, are usually found in the thoracic cavity, and a uterine origin is extremely rare. SFTs with insulin-like growth factor-II (IGF-II) production induce non-islet cell tumor-induced hypoglycemia (NICTH), referred to as Doege-Potter syndrome. CASE REPORT A 70-year-old woman presented with urinary retention, and imaging revealed a huge mass occupying almost the entire pelvic space. She had a history of hysterectomy for leiomyoma of the uterus 7 years earlier. In her present course, she developed hypoglycemia, and NICTH was suspected. Her previous uterine specimen was reexamined, and immunohistochemistry (IHC) revealed the specimen to be CD34-positive and alpha-smooth muscle actin-negative, indicating that the uterine specimen was not leiomyoma but SFT. Therefore, the present pelvic tumor was considered to be a recurrence of SFT with NICTH, namely Doege-Potter syndrome. Surgical resection was performed, and the pathological examination showed the same histologic features as the previous uterine specimen, while IHC revealed the present specimen to be positive for CD34, signal transducers and activator of transcription 6, and IGF-II, consistent with the diagnosis of recurrent SFT with IGF-II production. The patient's hypoglycemia improved after tumor resection. To confirm the IGF-II secretion from the SFT, we conducted immunoblotting of the patient's perioperative serum, with results showing that the strong band of IGF-II in the preoperative serum disappeared after surgery. CONCLUSIONS Because SFTs, especially those with Doege-Potter syndrome, often recur, sometimes with a very long interval, long-term cautious surveillance is required, even after complete tumor resection.

PBRM1 Immunohistochemical Expression Profile Correlates with Histomorphological Features and Endothelial Expression of Tumor Vasculature for Clear Cell Renal Cell Carcinoma.

Loss of the polybromo-1 (PBRM1) protein has been expected as a possible biomarker for clear cell renal cell carcinoma (ccRCC). There is little knowledge about how PBRM1 immunohistochemical expression correlates with the histomorphological features of ccRCC and the endothelial expression of tumor vasculature. The present study evaluates the association of architectural patterns with the PBRM1 expression of cancer cells using a cohort of 425 patients with nonmetastatic ccRCC. Furthermore, we separately assessed the PBRM1 expression of the endothelial cells and evaluated the correlation between the expression of cancer cells and endothelial cells. PBRM1 loss in cancer cells was observed in 148 (34.8%) patients. In the correlation analysis between architectural patterns and PBRM1 expression, macrocyst/microcystic, tubular/acinar, and compact/small nested were positively correlated with PBRM1 expression, whereas alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary, solid sheets, and sarcomatoid/rhabdoid were negatively correlated with PBRM1 expression. PBRM1 expression in vascular endothelial cells correlated with the expression of cancer cells (correlation coefficient = 0.834, p < 0.001). PBRM1 loss in both cancer and endothelial cells was associated with a lower recurrence-free survival rate (p < 0.001). Our PBRM1 expression profile indicated that PBRM1 expression in both cancer and endothelial cells may be regulated in an orchestrated manner.

Development and validation of a vascularity-based architectural classification for clear cell renal cell carcinoma: correlation with conventional pathological prognostic factors, gene expression patterns, and clinical outcomes.

The prognostic significance of an architectural grading system for clear cell renal cell carcinoma (ccRCC) has recently been demonstrated. The present study aimed to establish a vascularity-based architectural classification using the cohort of 436 patients with localized ccRCC who underwent extirpative surgery and correlated the findings with conventional pathologic factors, gene expression, and prognosis. First, we assessed architectural patterns in the highest-grade area on hematoxylin and eosin-stained slides, then separately evaluated our surrogate score for vascularity. We grouped nine architectural patterns into three categories based on the vascular network score. "Vascularity-based architectural classification" was defined: category 1: characterized by enrichment of the vascular network, including compact/small nested, macrocyst/microcystic, and tubular/acinar patterns; category 2: characterized by a widely spaced-out vascular network, including alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary patterns; category 3: characterized by scattered vascularity without a vascular network, including solid sheets, rhabdoid and sarcomatoid patterns. Adverse pathological prognostic factors such as TNM stage, WHO/ISUP grade, and necrosis were significantly associated with category 3, followed by category 2 (all p < 0.001). We successfully validated the classification using The Cancer Genome Atlas (TCGA) cohort (n = 162), and RNA-sequencing data available from TCGA showed that the angiogenesis gene signature was significantly enriched in category 1 compared to categories 2 and 3, whereas the immune gene signature was significantly enriched in category 3 compared to categories 1 and 2. In univariate analysis, vascularity-based architectural classification showed the best accuracy in pathological prognostic factors for predicting recurrence-free survival (c-index = 0.786). The predictive accuracy of our model which integrated WHO/ISUP grade, necrosis, TNM stage, and vascularity-based architectural classification was greater than conventional risk models (c-index = 0.871 vs. 0.755-0.843). Our findings suggest that the vascularity-based architectural classification is prognostically useful and may help stratify patients appropriately for management based on their likelihood of post-surgical recurrence.

Intimal regeneration after coronary endarterectomy and onlay grafting in coronary artery bypass grafting.

OBJECTIVES: Coronary onlay grafting, with or without endarterectomy, has been widely used for the treatment of diffuse lesions. Recent studies have demonstrated excellent long-term patency and favorable remodeling of onlay anastomosis; however, the underlying mechanisms remain unknown. Here, we describe the mechanism of intimal regeneration based on postmortem pathological evaluation of a patient who had undergone onlay grafting with coronary endarterectomy. METHODS: The onlay anastomosis was analyzed using a combination of immunohistological stainings, namely, H&E, vimentin, α-SMA, factor VIII, and Ki-67, to identify the source and mechanism of intimal regeneration after onlay grafting with endarterectomy. RESULTS: Our results suggest that the regenerated endothelium derives from the smooth muscle cells of the endarterectomized media of the coronary artery and that it circumferentially covers the internal lumen of the arterial graft. CONCLUSIONS: Intimal regeneration, derived from the smooth muscle cells of the endarterectomized coronary artery that proliferate toward the graft lumen, may be a key mechanism that underlies the observed favorable remodeling after onlay grafting during coronary endarterectomy.

Intestinal stem cells contribute to the maturation of the neonatal small intestine and colon independently of digestive activity.

The murine intestine, like that of other mammalians, continues to develop after birth until weaning; however, whether this occurs in response to an intrinsic developmental program or food intake remains unclear. Here, we report a novel system for the allotransplantation of small intestine and colon harvested from Lgr5 EGFP-IRES-CreERT2/+; Rosa26 rbw/+ mice immediately after birth into the subrenal capsule of wild-type mice. By histological and immunohistochemical analysis, the developmental process of transplanted small intestine and colon was shown to be comparable with that of the native tissues: mature intestines equipped with all cell types were formed, indicating that these organs do not require food intake for development. The intestinal stem cells in transplanted tissues were shown to self-renew and produce progeny, resulting in the descendants of the stem cells occupying the crypt-villus unit of the small intestine or the whole crypt of the colon. Collectively, these findings indicate that neonatal intestine development follows an intrinsic program even in the absence of food stimuli.

Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion.

Although the existence of cancer stem cells in intestine tumors has been suggested, direct evidence has not been yet provided. Here, we showed, using the multicolor lineage-tracing method and mouse models of intestinal adenocarcinoma and adenoma that Bmi1- or Lgr5- positive tumorigenic cells clonally expanded in proliferating tumors. At tumor initiation and during tumor propagation in the colon, the descendants of Lgr5-positive cells clonally proliferated to form clusters. Clonal analysis using ubiquitous multicolor lineage tracing revealed that colon tumors derived from Lgr5-positive cells were monoclonal in origin but eventually merged with neighboring tumors, producing polyclonal tumors at the later stage. In contrast, the origin of small intestine tumors was likely polyclonal, and during cancer progression some clones were eliminated, resulting in the formation of monoclonal tumors, which could merge similar to colon tumors. These results suggest that in proliferating intestinal neoplasms, Bmi1- or Lgr5-positive cells represent a population of cancer stem cells, whereas Lgr5-positive cells also function as cells-of-origin for intestinal tumors.

Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer.

We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. Although many Bmi1-positive cells within the tongue cancer specimens failed to proliferate, some proliferated continuously and supplied tumor cells to the surrounding area. This process eventually led to the formation of areas derived from single cells after 1-3 months, as determined using the multicolor lineage tracing method, indicating that such cells could serve as cancer stem cells. These results indicate that LESCs could serve as the origin for tongue cancer and that cancer stem cells are present in tongue tumors.

Maintenance of sweat glands by stem cells located in the acral epithelium.

The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.

Appendiceal diverticulitis: multidetector CT features.

PURPOSE: Appendiceal diverticulitis has been difficult to distinguish from acute appendicitis clinically and radiologically. The purpose of this study was to describe multidetector computed tomography (MDCT) features of cases of pathologically proved appendiceal diverticulitis at our institution over a 36-month period. MATERIALS AND METHODS: Seven of 156 patients who underwent appendectomy with the preoperative diagnosis of acute appendicitis were pathologically diagnosed with appendiceal diverticulitis. Two radiologists reviewed the MDCT images for these 7 patients. RESULTS: On MDCT, a total of 8 inflamed diverticula were visualized as small fluid-filled luminal structures with thick enhanced walls or as solid enhanced masses protruding from the appendix for 6 of 7 patients. For 2 of these 6 patients, MDCT revealed a total of 5 normal diverticula visualized as small air-filled luminal structures with thin walls. For 1 of the 7 patients, neither inflamed or normal diverticula could be identified on MDCT. MDCT revealed appendiceal wall thickening with a tiny or no luminal fluid collection for 5 patients and with a moderate fluid collection for 1 patient, and a normal appendiceal wall for 1 patient. CONCLUSION: Our results suggest that MDCT can reveal appendiceal diverticula and has potential in the preoperative diagnosis of appendiceal diverticulitis.