Insulin-like Growth Factor II mRNA-binding Protein 3 is a Highly Sensitive Marker for Intravascular Large B-cell Lymphoma: Immunohistochemical Analysis of 152 Pathology Specimens From 88 Patients.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive extranodal large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumina of blood vessels, particularly capillaries. IVLBCL lacks mass formation, and its diagnosis can be challenging. We analyzed the utility of insulin-like growth factor II mRNA-binding protein 3 (IMP3) immunohistochemistry for IVLBCL diagnosis in various organs. Double staining with paired box 5 (PAX5) was performed for validation. Overall, 152 pathological specimens (111 positive and 41 negative for IVLBCL) obtained from 88 patients with a diagnosis of IVLBCL were stained for IMP3 and IMP3/PAX5. As negative controls, 40 pathology specimens from 38 patients with no history of IVLBCL or other B-cell lymphomas were stained for IMP3, which comprised 31 benign pathological specimens from 29 patients in whom malignancy was suspected, 7 cases of appendicitis with intravascular and/or intralymphatic lymphoid proliferations, and 2 cases of intravascular natural killer/T-cell lymphoma. All mononuclear cells with cytoplasmic staining were considered positive for IMP3 expression, but expression restricted to germinal center B cells was excluded from evaluation. All 111 IVLBCL pathological specimens were positive for IMP3 and IMP3/PAX5. In addition, 11 of the 41 specimens originally diagnosed as IVLBCL-negative showed IMP3/PAX5 double-positive cells, raising the suspicion of IVLBCL. However, of the 40 negative control samples, IMP3-positive non-germinal center B cells were detected in only 2 samples ( P = 0.0131) and no intravascular IMP3-positive B cells suspicious for IVLBCL were identified. Altogether, IMP3 immunohistochemistry is a highly sensitive marker of IVLBCL and can be a helpful adjunct for IVLBCL diagnosis.

A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2.

ABSTRACT: An 87-year-old woman presented with a pedunculated nodule of 1.2 × 1.2 × 0.6 cm on her left cheek. Microscopic examination of the lesion revealed bowenoid and rosette-like basaloid components, resembling Bowen disease and neuroendocrine carcinoma, respectively. Immunohistochemically, both components were positive for Wnt signaling pathway molecules-nuclear/cytoplasmic beta-catenin, lymphoid enhancer binding factor 1 (LEF1), and caudal type homeobox 2 (CDX2)-and the adnexal marker SRY-box transcription factor 9 (SOX9). Unlike neuroendocrine tumors and basal cell carcinomas, the basaloid component in the present case was negative for chromogranin A, INSM1, synaptophysin, and p40. Previously reported cases of similar CDX2-positive lesions were diagnosed as squamous cell carcinoma with enteric adenocarcinomatous differentiation and basaloid cutaneous carcinoma with a primitive cytomorphology. However, the lesion in the present case was simultaneously positive for SOX9, indicating adnexal differentiation. In particular, the expression of multiple Wnt signaling pathway molecules indicates follicular differentiation despite the absence of morphological follicular features, such as shadow cells. Moreover, shared immunopositivity for SOX9, CDX2, nuclear/cytoplasmic beta-catenin, and LEF1 by both bowenoid and basaloid components indicated that the bowenoid component did not represent Bowen disease but a part of the adnexal tumor, and that the basaloid component was not a tumor-to-tumor metastasis. After complete excision, no recurrence has been observed for 5 months. The findings of the present case expand the histological spectrum of cutaneous adnexal tumors with follicular immunophenotypic differentiation.

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease.

Aims: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. Methods: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. Results: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). Conclusions: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

Low-grade B cell lymphoma in the perirenal space of the left kidney associated with high titer cold agglutinin disease.

Cold agglutinin disease (CAD) is a subgroup of autoimmune hemolytic anemia caused by monoclonal cold agglutinins produced by clonally expanded B lymphocytes. In primary CAD, lymphoproliferative bone marrow disorder is noted, while as one of the secondary cold agglutinin syndromes (CAS), the initial manifestation of CAD is followed by development of lymphoma. Here, we report a case of low-grade B cell lymphoma developed 3 months after an initial CAD diagnosis. The patient had an extremely high serum cold agglutinin titer (1:16,384) and slightly elevated serum IgM (452 mg/dL; reference, 31-200) with positive monoclonal IgM-kappa chain. After diagnosis of lymphoma-associated CAS, he was managed successfully with six cycles of a BR (bendamustine and rituximab) regimen. Cold agglutinin titers fell rapidly to 1:2048 at 5 months and to 1:512 at 10 months after chemotherapy, and the patient has been in a complete remission for 34 months.

Detection of tumor cells of serous tubal intraepithelial carcinoma (STIC) in cervical smears and rapid development of the ovarian involvement: A case report.

Serous tubal intraepithelial carcinoma (STIC) has attracted attention as a precursor lesion of high-grade serous carcinoma (HGSC) of the ovary. We report the rare case of a woman in whom adenocarcinoma cells were detected in cervical smears and demonstrated to be derived from STIC in the fimbria. The patient was a 48-year-old woman, in whom cervical smears contained adenocarcinoma cells, but cervical conization did not reveal adenocarcinoma. Because the post-conization smears again demonstrated adenocarcinoma cells, hysterectomy with bilateral salpingectomy was performed 16 months after the first detection of adenocarcinoma cells in cervical smears. Histopathological examination demonstrated STIC in the fimbria of the left fallopian tube. Bilateral ovaries appeared grossly normal at that time, but oophorectomy, which was performed 3 months later, disclosed HGSC involving the surface of bilateral ovaries. Detection of carcinoma cells from STIC in cervical smears is of marked significance for the management of patients, and we should keep in mind the possibility that adenocarcinoma cells in cervical smears are derived from STIC. The postoperative outcome of patients with STIC is considered generally favorable, and the clinical course of the present patient, in whom HGSC involving the bilateral ovaries was found shortly after salpingectomy, is exceptional.

Chondrolipoma of the breast as a rare variant of myofibroblastoma: an immunohistochemical study of two cases.

Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR). Chondrocytes were immunoreactive for ER, PgR, S-100 protein, and Sox9. The nuclei of adipocytes, chondrocytes, and spindle cells were not immunoreactive for Rb (retinoblastoma) protein. The immunoreactivity of spindle cells for muscle markers indicates myofibroblastic differentiation, and the lack of the nuclear expression of Rb protein suggests the close relationship of this tumor with myofibroblastoma and spindle cell lipoma. The immunoreactivity of chondrocytes for ER and PgR suggests that they are derived from metaplasia of hormone-sensitive spindle cells. These findings support the concept that chondrolipoma of the breast could be a lipomatous variant of myofibroblastoma associated with cartilaginous metaplasia and that it should be added to members of the "13q/Rb family of tumors."

SLC44A1-PRKCA fusion in papillary and rosette-forming glioneuronal tumors.

We investigated the fused protein of solute carrier family 44 choline transporter member 1 (SLC44A1) and protein kinase C alpha (PRKCA) in three patients with papillary glioneuronal tumors (PGNT). PGNT and rosette-forming glioneuronal tumors (RGNT) are recently identified, unusual glioneuronal tumor variants which were categorized as novel tumor entities in the 2007 World Health Organization classification system. The molecular background of these tumors remains poorly understood due to the paucity of studies. The SLC44A1-PRKCA fusion was recently detected in three cases of PGNT. We invesitgated for the SLC44A1-PRKCA fusion protein in the three PGNT patients and a further two with RGNT using fluorescence in situ hybridization. Two out of the three PGNT patients had a fused signal (paired red-green signal) representing a rearrangement on chromosomes 9 and 17. A normal signal pattern was observed in the third PGNT patient. Neither of the two RGNT patients demonstrated a fused signal. This suggests that the SLC44A1-PRKCA fusion is a characteristic alteration in PGNT but not RGNT. Therefore, it is a potential biomarker of PGNT. The paired red-green signal that was observed in the PGNT patients implies the presence of a different breakpoint than that previously reported in the 9q31 and 17q24 genes.

Primary borderline mucinous tumors of the testis: a case report and literature review.

Ovarian-type epithelial tumors of the testes and paratestes are very rare. Mucinous subtypes of such tumors are extremely rare; only 25 cases have been reported to date. Ovarian-type epithelial tumors are histologically classified into cystadenomas, borderline tumors, and carcinomas. We herein report a case involving a 60-year-old man with a primary borderline mucinous tumor of the testis. He underwent orchiectomy and has developed no recurrence for 4 years. This is the 26th report of a mucinous tumor of the testis in the literature. We also herein review the literature and discuss the etiology, prognosis, and treatment of mucinous tumors of the testes.

PD-1 regulates the growth of human mastocytosis cells.

BACKGROUND: Programmed death-1 (PD-1) is a marker for human neoplastic T cells. Here, we evaluated whether or not PD-1 was also a marker for human mastocytosis, and explored the role of PD-1 in human mastocytosis cells. METHODS: Immunohistochemical analysis was used to evaluate the expression of PD-1 in clinical samples of human cutaneous mastocytosis. The expression of PD-1 in human mastocytosis cell lines was checked by RT-PCR, western blotting and flow cytometry. We stimulated human mastocytosis cell lines (LAD2 and HMC1.2) with recombinant ligand for PD-1, PD-L1 (rPD-L1), and tested the proliferative activity and the status of signal molecules by Cell Counting Kit-8 and ELISA, respectively. RESULTS: Ten of 30 human cutaneous mastocytosis cases (33.3%) expressed PD-1 protein. We also found that a human mastocytosis line LAD2 cells expressed PD-1 protein on their surfaces. The administration with rPD-L1 suppressed the stem cell factor-dependent growth of the LAD2 cells. And, rPD-L1 activated SHP-1 and SHP-2 simultaneously, and decreased the phosphorylation of AKT, in LAD2 cells. In contrast, we could not detect the expression of PD-1, and the significant effect of rPD-L1 on the mutated KIT-driven growth of HMC1.2 cells. CONCLUSIONS: PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.

Xanthogranulomatous cholecystitis complicated with primary sclerosing cholangitis: report of a case.

Patients with primary sclerosing cholangitis (PSC) are at an increased risk for biliary tract carcinoma. The preoperative diagnosis of a biliary tract tumor as a malignancy is difficult, even using new modalities such as multidetector computed tomography (MD-CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiography (ERC), and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Surgery is considered to be first line of treatment when these examinations suggest the presence of malignancy in the biliary tract, depending on both the curability of the cancer and the impaired liver function due to PSC. The management of gallbladder masses in patients with PSC remains problematic due to difficulties with the precise diagnosis and adequate surgery. Xanthogranulomatous cholecystitis (XGC) is a type of chronic cholecystitis, and sometimes coexists with gallbladder cancer. It is very difficult to make a preoperative diagnosis differentiating these two diseases. This report presents the case of a patient with XGC, who had been suspected of having gallbladder cancer before surgery, because the tumorous lesion emerged within a year and showed a focally increased uptake by FDG-PET during the follow up for PSC for years. This is the first case of XGC discovered during treatment for PSC.