Masatoshi Tateno

Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor II

A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61‐year‐old man with frequent hypoglycemia. Endocrinological analyses showed high serum levels of insulin‐like growth factor II (IGF‐II) and suppressed secretion of insulin. After the removal of a pleural tumor, which weighed 3150g, serum IGF‐II levels returned to normal and hypoglycemic attacks ceased. The tumor was composed of uniform spindle cells arranged in bundles, and fascicles with varying amounts of collagen and retlculin fibers. Mitotlc figures at the rate of 6/10 high‐power fields, and frequent foct of necrosis and hemorrhage were seen. Almost all of the tumor cells were Immunohlstochemically positive for vimentin and CD34. Electron microscopy revealed the immature mesenchymal or myofibroblastic nature of the tumor cells. These findings are consistent with malignant SFT of the pleura. Moreover, the tumor produced IGF‐II mRNA as demonstrated by northern blot analysis. Thus, hypoglycemia of this patient was induced by SFT through the production and secretion of IGF‐II.

IMMUNOPATHOLOGICAL STUDIES OF AN AUTOPSY CASE WITH GOODPASTURE'S SYNDROME AND SYSTEMIC NECROTIZING ANGIITIS

A rare autopsy case of Goodpastures syndrome with systemic necrotizing angiitis is reported. The patient, a 56‐year‐old male, died of respiratory failure with massive pulmonary hemorrhage and renal failure. The autopsy showed widespread hemorrhage In both lungs, diffuse crescentic glomerulonephrltis, and systemic necrotizing angiitis in the small arteries. Immunofluorescence studies demonstrated a linear deposition of IgG along the glomerular basement membrane (GBM) as well as the alveolar basement membrane. A granular deposition of C3 was also found along the GBM. Electron microscopy showed that the GBM was Irregularly thickened and wrinkled, but electron‐dense deposits were indistinct. Anti‐GBM antibody activity was detected in the patients serum and had cross reactivity with normal alveolar basement membrane. The renal eluates contained IgG antibody activity for normal human GBM. These results suggest that glomer‐ulonephritis and pulmonary hemorrhage in the present case were mediated by anti‐basement membrane antibodies. We also discussed whether antibasement membrane antibody is involved in the pathogenesis of systemic necrotizing angiitis.

Colonic inflammatory fibroid polyp with PDGFRA expression

To the Editor: Inflammatory fibroid polyp (IFP) is an uncommon mesenchymal neoplasm of the gastrointestinal tract. IFPs occur in the esophagus, stomach, and small and large intestines in adults of all ages. They sometimes cause gastrointestinal hemorrhage and intestinal obstruction. The typical histological appearance is a proliferation of spindle cells and blood vessels with inflammatory infiltrates containing eosinophils. We report a case of colonic IFP in a 53-year-old woman who underwent colonoscopy to identify the cause of bloody stool. Endoscopic examination of the large intestine revealed a pedunculated polypoid lesion in the descending colon (Fig. 1a), and endoscopic mucosal resection was performed. The lesion measured 35 33mm, with no ulceration. On cross-section, the head portion of the polypoid lesion was uniformly whitish and solid (Fig. 1b). Histologically, bland spindle cells without nuclear atypia proliferated in the mucosa and submucosa with an edematous matrix. Many blood vessels with surrounding edematous change proliferated in the submucosa. Spindle cells were concentrically arranged around the vessels, showing a distinctive onion-skin pattern (Fig. 1c). The lesion showed severe infiltration of inflammatory cells consisting of mainly eosinophils in addition to lymphocytes, plasma cells, and histiocytes (Fig. 1d). Immunohistochemistry (IHC) showed that the spindle cells were diffusely positive for platelet-derived growth factor receptor alpha (antiPDGFRA rabbit monoclonal antibody D13C6) (Fig. 1e) and were focally positive for alpha smooth muscle actin (aSMA) and CD34 (Fig. 1f). The spindle cells were negative for c-kit, DOG1, and ALK. We also checked for activating mutations in exons 12, 14, and 18 of the PDGFRA gene by direct sequencing, but no mutations were found. Our differential diagnoses included inflammatory myofibroblastic tumor (IMT) and angiolymphoid hyperplasia with eosinophilia (ALHE). IMT is a rare mesenchymal tumor that occurs throughout the body. Histologically, myofibroblastic and fibroblastic spindle cells proliferate, with infiltration of plasma cells, lymphocytes, and eosinophils. Myxoid stroma with abundant blood vessels may be present. IHC shows that spindle cells are positive for aSMA and negative for CD34. Rearrangements of the ALK gene locus on 2p23 have been reported in 50–70% of cases, and ALK protein overexpression can be detected on IHC. In our case, the spindle cells expressed aSMA and CD34, and did not show immunoreactivity for ALK. Considering our IHC findings, we excluded IMT as a diagnosis. Angiolymphoid hyperplasia with eosinophilia is a benign tumor that mainly occurs on the skin around the head and neck. Colonic ALHE is extremely rare, and to the best of our knowledge, there have been only three reports of ALHE in the colon to date. Histologically, ALHE shows proliferation of immature blood vessels, with infiltration of eosinophils and lymphocytes. Endothelial cells in ALHE have a characteristic epithelioid or histiocytoid appearance. In our case, vascular proliferation and infiltration of eosinophils suggested that the lesion could be ALHE. However, we diagnosed it as IFP because there were no epithelioid endothelial cells in the blood vessels, and there was a characteristic onion-skin pattern of spindle cells around the vessels. Moreover, IHC indicated PDGFRA expression in the spindle cells, which enabled us to distinguish the case from ALHE. Mutations of the PDGFRA gene have been shown to be oncogenic in the subset of gastrointestinal stromal tumors (GIST) that lack c-kit mutations. Recent studies have demonstrated that a significant proportion of IFPs harbor mutations in the PDGFRA gene, suggesting that IFPs are not a reactive lesion but rather a true neoplasm. Exon 12 mutations predominate in small intestinal IFPs, while exon 18 mutations occur mainly in gastric IFPs. In the colon, only one of four reported IFPs had the point mutation D842V in PDGFRA exon 18. Including our present case, one of five colonic IFPs have been reported to harbor this mutation, which suggests that PDGFRA mutations are uncommon in colonic IFPs. Tumor cells of GIST with PDGFRA mutations have been found to show epithelioid morphology and PDGFRA immunoreactivity with perinuclear dot-like expression. In the present case, the IFP tumor cells were diffusely positive for PDGFRA, but dot-like staining was not observed. Genetically, there were no mutations in the PDGFRA exons. We previously reported a case of a gastric IFP in a 73-year-old man. The polyp was removed endoscopically and pathologically diagnosed as an IFP. On IHC, the spindle cells of this IFP also diffusely expressed PDGFRA. Direct DNA sequencing of exons 12, 14, and 18 in PDGFRA did not reveal any mutations. Our two IFP cases suggest that diffuse PDGFRA expression on IHC in IFPs is not a predictor of a true PDGFRA gene mutation.

Muellerian adenosarcoma of the uterus. Report of two cases.

子宮体部に発生したMullerian adenosarcomaを2例経験した.症例1は, 67歳女性.不正性器出血で来院. 内膜細胞診, 組織診にて悪性疾患を否定し得ず, 子宮全摘術施行. 子宮後壁から子宮内腔を充満する7×7×3cm大のカリフラワー状腫瘍を認めた. 症例2は, 55歳女性. 不正性器出血で来院. 外子宮口から腔内へ脱出した腫瘍を認めたため, 子宮全摘術施行. 子宮底部に基底部を有し頸部をこえて脱出した12×5×6cm大の有茎性腫瘍を認めた. 術後6年4ヵ月, 肺転移にて死亡した. 2例とも病理組織学的にはadenosarcomaの典型例であった.細胞診所見では, 上皮成分に悪性を示唆する異型性はみられず, 内膜腺様細胞, 頸管腺様細胞, 扁平上皮化生細胞, tissue repair cell様細胞など多彩な形態を示していた. ミュラー管由来の上皮はさまざまな形態に分化する可能性があり, 閉経婦人の内膜標本で一般にみられない上皮細胞が出現する場合はadenosarcomaを考慮する必要があると考える. 診断の決め手は, 肉腫様の異型細胞の出現を確認することであるが, ごく少数しかみられない場合があり, 間質細胞の集塊が目立つ場合には, 積極的に再検, 生検を行う必要があると考える.

A JAPANESE BURKITT'S LYMPHOMA WITH t(2;8) AND EBNA

A 56‐year‐old Japanese man was admitted to the hospital with a large mass in his right axilla. Histological investigation revealed that it was a Burkitts lymphoma. Ultrastructures of the tumor cells showed immature lymphoid features with frequent lipid droplets within the cytoplasms. Virological studies before the treatment revealed that the lymphoma was closely related to EB virus infection, being positive for EBNA (more than 95% of all tumor cells) and IgG antibodies to VCA (× 5, 120), EA (× 640), and EBNA (× 160). The tumor cells exhibited low levels of cytoplasmic IgM and other properties of B cells. They were positively stained with L26, L27, Leu 14, and HLA‐DR MAb. In cultured tumor cells, L25 and CALL? antigens were demonstrated, but no surface Ig was shown. In contrast, the tumor cells were negative for T cell markers including AcP, E‐receptor, and Leu 1, 2, and 3. Cytogenetic studies demonstrated that the karyotype of the tumor cells was 46, XY, dup (1q), t(2; 8)/46, X, ‐Y, t(2;8), +mar. VEMP therapy was immediately conducted. However, following a two‐month partial remission, a relapse with bone marrow infiltration occurred. Thus, a case of Japanese Burkitts lymphoma with EBNA (+) and t(2;8) properties is described, and the relationships among primary sites, phenotypes, and genotypes are discussed.

Clinicopathology and Immunopathology of 80 Biopsy Cases

The clinicopathology and immunopathology of 80 cases of lupus nephritis in a total of 1,187 biopsies were presented. Histologically, they consisted of 11 cases of mesangial lupus nephritis (13.8%), 51 cases of diffuse proliferative lupus nephritis (63.7%), and 18 cases of membranous lupus nephritis (22.5%). No cases of focal proliferative type, minimal changes or end‐stage kidneys were included. Ten cases were male and they had no qualitative and quantitative differences with female ones in any respects. The microtubular structures were found in glomerular endothelial cells with a 70% frequency and in the interstitial endothelial cells with a 46% frequency. In the latter case, microtubular structures tended to be localized in the perinuclear space as well as in the endoplasmic reticulum. Spherical microparticles were found in 46% of all cases and the incidences were significantly higher in the membranous type. Organized deposits with straight parallel microfilaments were found only in a single case. Electron‐dense deposits with fingerprint pattern were not seen. Immunohistochemically, various immunoglobulins, complement components, and fibrinogen were found deposited more frequently in diffuse proliferative lupus nephritis. IgG was the predominant immunoglobulin deposited in capillary loops in membranous types, and IgA in the mesangium in mesangial types. Extraglomerular deposition of immunoglobulins and complements were found in 26.3% of all cases.