[A Rare Case of Primary Splenic Malignant Lymphoma Associated with Esophagogastric Junction Neuroendocrine Carcinoma(NEC)].

A 75-year-old man was showed wall thickening just below esophagogastric junction(EGJ)by gastroscopy(GS). Biopsy indicated mucinous carcinoma. He was referred to our hospital. Computed tomography(CT), PET-CT showed EGJ cancer and splenic tumor. EGJ cancer was diagnosed GE, Siewert Type Ⅱ, GrePostAnt, Type 1, cT2, cN0, cM0, cStage Ⅰ. The patient underwent total gastrectomy, lower esophagectomy, D2+ #19, 20, 110, 111, 112 lymph nodes dissection, Rou-en- Y reconstruction, distal pancreatectomy, splenectomy, cholecystectomy, and enterostomy. Postoperative complication was pancreatic fistula(Grade Ⅱ). Pathological diagnosis was esophagogastric junction cancer, neuroendocrine carcinoma(NEC), GE, Siewert Type Ⅱ, GrePostAnt, Type 1, pT2(MP), pN1, pM0, pStage ⅡA. Splenic tumor was diagnosed splenic malignant lymphoma, large B-cell, diffuse(DLBCL), NOS, low-immediate risk. Patient was discharged 15 days after the operation and underwent adjuvant chemotherapy with S-1. In this case, he started taking S-1 because the prognosis of NEC is poorer than PSML. There was no evidence of recurrence after 5 months from gastrectomy. As a result of searching for"neuroendocrine tumor"and"malignant lymphoma"in the JAMAS, there was no report of NEC associated with malignant lymphoma. We experienced the rare case of primary splenic malignant lymphoma associated with EGJ NEC. In the case of gastric cancer with splenic tumor, malignant lymphoma of spleen should be concerned.

[A Case of Laparoscopic Total Gastrectomy for Juvenile Polyposis of Stomach with Synchronous Multiple Intramucosal Carcinomas].

The patient was a 57-year-old woman. She was referred to our hospital because severe anemia. Upper gastrointestinal endoscopy revealed polyposis throughout the stomach and lobulated polyps in cardia, greater curve of middle body of the stomach, and angulus. Colonoscopy and small bowel endoscopy showed no obvious abnormal findings. Based on these findings, a laparoscopic total gastrectomy with D1 lymph node dissection was performed for suspected juvenile polyposis of stomach with severe anemia. The gross examination of the resection specimen revealed diffuse polyposis throughout the stomach, and histopathological examination revealed hyperplasia of the orbital epithelium throughout the stomach and lack of edema in lamina propria of mucous and eosinophil leukocytic infiltration, leading to the diagnosis of juvenile polyposis of stomach. Two well differentiated adenocarcinomas were found in 2 locations, which remained within the mucosa. We report a case of laparoscopic total gastrectomy for juvenile polyposis of the stomach with gastric cancer, with some discussion of the literature.

[Mucinous Adenocarcinoma of the Prostate Diagnosed after Transurethral Treatment of a Prostatic Abscess].

A 70-year-old man visited his doctor because of hip pain and gross hematuria. Digital rectal examination and computed tomography revealed a prostatic abscess. Although antibiotics were prescribed, his symptoms did not improve; he was transferred to our hospital, where transurethral fenestration of the prostatic abscess was performed. During prostatic fenestration, a papillary mucous membrane was confirmed inside the cavity of the prostatic abscess. Pathological examination revealed a mucinous adenocarcinoma of the prostate. Although hormonal therapy was administered, magnetic resonance imaging revealed tumor extension necessitating robot-assisted radical prostatectomy. Mucinous adenocarcinoma of the prostate is rare, and to our knowledge this is the first report of mucinous adenocarcinoma of the prostate diagnosed after transurethral treatment of a prostatic abscess.

[A Case of Gastric Cancer Treated with Resection and Adjuvant Chemotherapy in Japan after FOLFOX Neoadjuvant Chemotherapy in USA].

A 73‒year‒old man, living in the United States since 1985, visited the University of Minnesota Medical Center with a complaint of upper abdominal pain in December 2019. Gastroendoscopy revealed a depressed lesion in the U area of the stomach, and the biopsy results indicated a diagnosis of por/sig. On further examination, the condition was diagnosed as gastric cancer of cStage II/III. A gastrectomy procedure was planned after treatment with neoadjuvant chemotherapy(NAC). After 1 course of mFOLFOX6, the patient decided to undergo treatment in Japan. He travelled to Japan in February and visited our hospital. In March, he underwent total gastrectomy plus D2 dissection plus Roux‒en‒Y reconstruction. The final diagnosis was gastric cancer, U, Less, ypType 2, ypT3(ss), ypN1, sM0, yfStage IIB, and the therapeutic effect was Grade 2. DS therapy was started as adjuvant chemotherapy in April. After 8 courses, he returned to the United States. After moving to the United States, he personally imported S‒1 and continued adjuvant chemotherapy at the University of Minnesota Hospital. The guidelines in Japan do not recommend NAC. Given that Grade 2 therapeutic effect was obtained even with 1 course of the treatment, FOLFOX therapy could be effective as preoperative chemotherapy for advanced gastric cancer cases.

Measurement of telomere length in cells from pleural effusion: Asbestos exposure causes telomere shortening in pleural mesothelial cells.

We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial cells and examined their correlation with asbestos exposure and the expression of markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from 35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM) and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-). Telomere length was measured using the tissue quantitative fluorescence in situ hybridization method, and expressed as normalized telomere-to-centromere ratio. NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P < 0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp- cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases with shorter telomeres tended to show aberrant expression of epithelial membrane antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA-binding protein 3 (IMP3). These results suggest that telomere shortening and subsequent genetic instability play an important role in the development of MM. Measurement of telomere length of cells in pleural effusion might be helpful for earlier detection of MM.

Clinicopathological and Prognostic Evaluations of Mixed Adenoneuroendocrine Carcinoma of the Colon and Rectum: A Case-Matched Study.

BACKGROUND: Mixed adenoneuroendocrine carcinoma of the colon and rectum is a very rare type of tumor. OBJECTIVE: The aim of the present study was to evaluate the clinicopathological characteristics and prognosis of mixed adenoneuroendocrine carcinomas of the colon and rectum. DESIGN: This was a retrospective case-matched analysis (from March 2007 to December 2013). SETTINGS: This study was conducted at Yokosuka Kyosai Hospital. PATIENTS: One thousand three hundred six consecutive patients with a preoperative diagnosis of colorectal cancer and who underwent tumor resection were enrolled in the present study. Each patient diagnosed with mixed adenoneuroendocrine carcinoma was 1:2 matched with 2 counterparts who had been diagnosed with adenocarcinoma. INTERVENTION: Immunohistochemical staining for neuroendocrine markers (chromogranin A, synaptophysin, and CD56) was performed. Cases in which the neuroendocrine component accounted for >30% of the tumor were diagnosed as mixed adenoneuroendocrine carcinomas. RESULTS: Among 1306 patients, 42 patients (3.2%) were diagnosed with mixed adenoneuroendocrine carcinoma and were compared with 84 patients with adenocarcinoma who had been randomly case matched. The average Ki-67-labeling index value was 78.0% (range, 30.0%-99.0%). Chromogranin A, synaptophysin, and CD56 positivity were observed in 42.9% (18/42), 81.0% (34/42), and 33.3% (14/42) of the tumors. Both the disease-free survival and overall survival were significantly worse for mixed adenoneuroendocrine carcinoma than for adenocarcinoma. Ten patients underwent treatment with oxaliplatin-based chemotherapy. The response rate was 40.0%; the median progression-free survival and overall survival were 6.3 months and 18.1 months. LIMITATIONS: This was a retrospective single-institution study that included a limited number of cases. The treatment regimens used included different types of oxaliplatin-based chemotherapy. CONCLUSION: Mixed adenoneuroendocrine carcinoma of the colon and rectum has a poor prognosis after curative resection and should be distinguished from adenocarcinoma.

[A Case of Synchronous Malignant Pheochromocytomas in Bilateral Adrenal Glands].

We present a case of synchronous malignant pheochromocytoma in bilateral adrenal glands. A 73- year-old man presented to our hospital with bilateral adrenal masses incidentally found during abdominal ultrasonography examination for an unrelated issue. The patient had a 30-year history of hypertension and paroxysmal atrial fibrillation. Computed tomography and magnetic resonance imaging showed heterogeneous tumors in bilateral adrenal glands and an enlarged para-aortic lymph node. Hormonal examinations revealed a high value of urinary catecholamines. Metaiodobenzylguanidine (MIBG) scintigraphy showed increased uptake in bilateral adrenal glands and the lymph node. Both adrenal tumors and the node were surgically removed. Pathological examination revealed histologically distinct tissue between the two adrenal tumors. The patient received five cycles of adjuvant chemotherapy, consisting of cyclophosphamide, vincristine, and dacarbazine. The patient has been in remission for 32 months following surgical treatment.

[Undifferentiated carcinoma of the jejunum producing granulocyte colony-stimulating factor].

An 80-year-old man presented with abdominal fullness and vomiting. Laboratory data revealed severe anemia, an inflammatory response, and elevated white blood cell counts. Abdominal computed tomography indicated ileus caused by a jejunal tumor measuring 8cm in diameter. Although small-bowel endoscopy enabled visualization of the tumor, adequate biopsy specimens could not be obtained for accurate diagnosis. The patient's condition rapidly deteriorated, because of which surgical treatment could not be initiated. The patient died approximately 3 weeks after admission. High serum granulocyte colony-stimulating factor (G-CSF) levels were detected at autopsy. Immunohistochemical staining of the autopsy specimen indicated positive G-CSF levels in the jejunal tumor. On the basis of these findings, a final diagnosis of undifferentiated carcinoma of the jejunum producing G-CSF was made.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

OBJECTIVES: Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. METHODS: A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. RESULTS: A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). CONCLUSIONS: Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Post-staphylococcal infection Henoch-Schönlein purpura nephritis: a case report and review of the literature.

A 37-year-old man developed Henoch--Schönlein purpura nephritis (HSPN) with nephrotic syndrome and rapidly progressive glomerulonephritis after otitis media and externa due to methicillin-resistant Staphylococcus aureus infection. Despite resolution of the infection and prednisolone therapy, his kidney disease worsened. However, the addition of cyclosporine A finally resulted in complete remission of the nephrotic syndrome. A review of similar cases with post-Staphylococcal infection HSPN revealed strong similarities between this entity and immunoglobulin A-dominant postinfectious glomerulonephritis (IgA-PIGN), an increasingly recognized form of PIGN typically associated with Staphylococcal infection, in both clinical and morphological features. Post-Staphylococcal infection HSPN may constitute a subgroup of IgA-PIGN.

Breast carcinoma with spontaneous regression after needle biopsy: a case report and literature review.

Background: Spontaneous regression (SR) of cancer is a rare condition in which the cancer partially or completely disappears without treatment. We report a case of breast cancer with tumor regression and spontaneously induced T-cell-mediated immunological responses in a surgical specimen obtained after core needle biopsy (CNB). Case Description: A 52-year-old woman presented with a mass in the right breast. Mammography showed a high-density mass with fine serrated margins in the right lower outer quadrant. Breast ultrasonography showed an irregular hypoechoic mass with a maximum diameter of 22 mm. CNB was performed and revealed an invasive ductal carcinoma with negative estrogen receptors, positive progesterone receptors, and negative HER2 (1+). The Ki67 index was 70% to 80%. Luminal B cT2N1M0 stage IIB right breast cancer was diagnosed. Although preoperative chemotherapy was considered, surgery was selected because of her history of schizophrenia. She underwent right mastectomy and axillary lymph node dissection. A postoperative pathological analysis revealed a 20 mm × 10 mm × 10 mm mass. However, most areas of the mass regressed and appeared as necrotic tissue with no obvious invasive areas. Only intraductal extension was observed in one glandular duct. Axillary lymph node metastases were not observed. These results suggest that the tumor may have spontaneously regressed, possibly because of the CNB procedure. Follow-up without treatment was performed, and no recurrence occurred during 2 years after surgery. Conclusions: Invasive ductal carcinoma may spontaneously regress after preoperative CNB.

Sunitinib-induced nephrotic syndrome and irreversible renal dysfunction.

Sunitinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), has become essential for treating imatinib-resistant malignant gastrointestinal stromal tumor. Recently, several cases have been reported that showed proteinuria and kidney dysfunction to be associated with anti-VEGF therapy. Although previous reports indicated that this side-effect is reversible, it is not well understood. We present here the case of a 72-year-old man who presented with nephrotic syndrome and renal dysfunction 6 months after administration of sunitinib. Sunitinib was discontinued, and nephrotic syndrome remitted spontaneously, but renal function recovery was limited. Nine months later, a renal biopsy was performed because sunitinib was again required and pathological examination was needed. The renal biopsy showed marked endothelial cell injury with focal segmental glomerulosclerosis and accelerated VEGF expression by podocytes. Sunitinib was then given at a reduced dose. Kidney dysfunction and nephrotic syndrome are rare but serious complications of sunitinib. The present case suggests that long-term treatment with a high dose of sunitinib can cause irreversible renal dysfunction, and that low-dose treatment makes these side-effects manageable.

Malignant pleural mesothelioma in situ.

Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.

Membranous nephropathy in a patient with pulmonary tuberculosis infection and lung adenocarcinoma: a case report.

We report a case of membranous nephropathy (MN) in a patient with tuberculosis infection and lung adenocarcinoma. A 50-year-old Filipino woman underwent a renal biopsy for the evaluation of proteinuria and hematuria. Immunofluorescence analysis revealed positive staining of IgG in the glomerular basement membrane and mesangial matrices, while electron microscopy demonstrated the presence of sub-epithelial deposits, suggesting MN. To screen for secondary causes of MN, we conducted a computed tomography (CT) scan of the chest and abdomen, which revealed a ground-glass opacity in the middle lobe of the right lung and an enlarged paraaortic lymph node. A T-SPOT test was positive, suggesting the possibility of a latent tuberculosis infection, as she was asymptomatic. A follow-up chest CT scan showed persistent presence of the ground-glass opacities, suggesting a non-infectious cause. Video-assisted thoracoscopic resection of the middle right lobe and partial resection of the lower right lobe were performed because the possibility of lung cancer could not be excluded. Notably, pathological analysis of the lung revealed adenocarcinoma in the middle lobe and epithelioid granuloma in the lower lobe, suggesting an active tuberculosis infection. One month after surgery, anti-tuberculosis treatment was initiated. Thereafter, her proteinuria, which had increased to 6 g/gCre preoperatively, began to decrease. Five months after surgery, the patient achieved complete remission. The speed of remission suggests that tuberculosis likely played a primary role in the etiology of MN. Our case underscores the importance of screening tests for infections and malignancies in patients with MN, even if suggestive symptoms are absent.

Paraneoplastic Cerebellar Degeneration With P/Q-VGCC vs Yo Autoantibodies.

BACKGROUND AND OBJECTIVES: Paraneoplastic cerebellar degeneration (PCD) is characterized by a widespread loss of Purkinje cells (PCs) and may be associated with autoantibodies against intracellular antigens such as Yo or cell surface neuronal antigens such as the P/Q-type voltage-gated calcium channel (P/Q-VGCC). Although the intracellular location of the target antigen in anti-Yo-PCD supports a T cell-mediated pathology, the immune mechanisms in anti-P/Q-VGCC-PCD remain unclear. In this study, we compare neuropathologic characteristics of PCD with anti-P/Q-VGCC and anti-Yo autoantibodies in an archival autopsy cohort. METHODS: We performed neuropathology, immunohistochemistry, and multiplex immunofluorescence on formalin-fixed and paraffin-embedded brain tissue of 1 anti-P/Q-VGCC, 2 anti-Yo-PCD autopsy cases and controls. RESULTS: Anti-Yo-PCD revealed a diffuse and widespread PC loss together with microglial nodules with pSTAT1+ and CD8+granzymeB+ T cells and neuronal upregulation of major histocompatibility complex (MHC) Class I molecules. Some neurons showed a cytoplasmic immunoglobulin G (IgG) staining. In contrast, PC loss in anti-P/Q-VGCC-PCD was focal and predominantly affected the upper vermis, whereas caudal regions and lateral hemispheres were spared. Inflammation was characterized by scattered CD8+ T cells, single CD20+/CD79a+ B/plasma cells, and an IgG staining of the neuropil in the molecular layer of the cerebellar cortex and neuronal cytoplasms. No complement deposition or MHC-I upregulation was detected. Moreover, synaptophysin was reduced, and neuronal P/Q-VGCC was downregulated. In affected areas, axonal spheroids and the accumulation of amyloid precursor protein and glucose-regulated protein 78 in PCs indicate endoplasmatic reticulum stress and impairment of axonal transport. In both PCD types, calbindin expression was reduced or lost in the remaining PCs. DISCUSSION: Anti-Yo-PCD showed characteristic features of a T cell-mediated pathology, whereas this was not observed in 1 case of anti-P/Q-VGCC-PCD. Our findings support a pathogenic role of anti-P/Q-VGCC autoantibodies in causing neuronal dysfunction, probably due to altered synaptic transmission resulting in calcium dysregulation and subsequent PC death. Because disease progression may lead to irreversible PC loss, anti-P/Q-VGCC-PCD patients could benefit from early oncologic and immunologic therapies.

A Novel LMX1B Variant Identified in a Patient Presenting with Severe Renal Involvement and Thin Glomerular Basement Membrane.

We report a case of nail-patella syndrome (NPS) with unusual thinning of the glomerular basement membrane (GBM) associated with a novel heterozygous variant in the LMX1B gene. A 43-year-old female patient with a previous diagnosis of NPS, referred to our hospital for persistent proteinuria, underwent a renal biopsy, which revealed minor glomerular abnormalities. She underwent a second renal biopsy at the age of 56 owing to the presence of persistent proteinuria and decline in serum albumin, meeting the diagnostic criteria for nephrotic syndrome. Light microscopy demonstrated glomerulosclerosis and cystic dilatation of the renal tubules. Notably, electron microscopy revealed unusual thinning of the GBM, which is quite different from typical biopsy findings observed in patients with NPS, characterized by thick GBM with fibrillary material and electron-lucent structures. Comprehensive genetic screening for 168 known genes responsible for inherited kidney diseases using a next-generation sequencing panel identified a novel heterozygous in-frame deletion-insertion (c.723_729delinsCAAC: p.[Ser242_Lys243delinsAsn]) in exon 4 of the LMX1B gene, which may account for the disrupted GBM structure. Further studies are warranted to elucidate the complex genotype-phenotype relationship between LMX1B and proper GBM morphogenesis.

Neuropathology of SCA34 showing widespread oligodendroglial pathology with vacuolar white matter degeneration: a case study.

Spinocerebellar ataxia type 34 (SCA34) is an autosomal dominant inherited ataxia due to mutations in ELOVL4, which encodes one of the very long-chain fatty acid elongases. SCA38, another spinocerebellar ataxia, is caused by mutations in ELOVL5, a gene encoding another elongase. However, there have been no previous studies describing the neuropathology of either SCA34 or 38. This report describes the neuropathological findings of an 83-year-old man with SCA34 carrying a pathological ELOVL4 mutation (NM_022726, c.736T>G, p.W246G). Macroscopic findings include atrophies in the pontine base, cerebellum, and cerebral cortices. Microscopically, marked neuronal and pontocerebellar fiber loss was observed in the pontine base. In addition, in the pontine base, accumulation of CD68-positive macrophages laden with periodic acid-Schiff (PAS)-positive material was observed. Many vacuolar lesions were found in the white matter of the cerebral hemispheres and, to a lesser extent, in the brainstem and spinal cord white matter. Immunohistological examination and ultrastructural observations with an electron microscope suggest that these vacuolar lesions are remnants of degenerated oligodendrocytes. Electron microscopy also revealed myelin sheath destruction. Unexpectedly, aggregation of the four-repeat tau was observed in a spatial pattern reminiscent of progressive supranuclear palsy. The tau lesions included glial fibrillary tangles resembling tuft-shaped astrocytes and neurofibrillary tangles and pretangles. This is the first report to illustrate that a heterozygous missense mutation in ELOVL4 leads to neuronal loss accompanied by macrophages laden with PAS-positive material in the pontine base and oligodendroglial degeneration leading to widespread vacuoles in the white matter in SCA34.