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.

Development of male breast cancer in a patient with prostate cancer during androgen deprivation therapy.

INTRODUCTION: Male breast cancer accounts for <1% of all breast cancer. We report a patient with prostate cancer during hormone therapy who developed breast cancer. CASE PRESENTATION: An 88-year-old male underwent androgen deprivation therapy for prostate cancer and developed an induration in the left breast 7 years after the start of treatment. After close examination, he was diagnosed with left breast cancer with lymph node metastasis. The prostate cancer was stable in a hormone-sensitive state. Left mastectomy was performed and the pathological diagnosis was invasive ductal carcinoma. DISCUSSION: In addition to our patient, seven patients who developed breast cancer during hormone therapy for prostate cancer were examined. Five of six patients had stage II or above, and four patients had lymph node metastases. Although local breast symptoms are frequently observed as adverse effects of hormone therapy, caution is warranted regarding male breast cancer.

Muscle invasive urinary bladder urothelial carcinoma presenting with secondary nephrotic symptoms.

INTRODUCTION: Nephrotic syndrome secondary to malignant disease accounts for approximately 10% of cases of nephrotic syndrome in adults. However, urothelial carcinoma of the bladder is a rare cancer, with only four cases reported to date. CASE PRESENTATION: A 76-year-old man presented with chief complaints of edema and anorexia. Laboratory examinations revealed hypoalbuminemia and marked proteinuria, and computed tomography demonstrated multiple bladder tumors. Transurethral resection of the bladder tumors was performed. The pathological diagnosis was urothelial carcinoma with muscular invasion. The patient underwent simple cystectomy and ileal conduit formation, and proteinuria disappeared after 4 weeks. However, urethral recurrence was noted, and he died 35 months after cystectomy. CONCLUSION: Five cases including ours were clinically reviewed. Nephrotic symptoms improved relatively rapidly after surgery in all cases. In contrast to the poor preoperative general condition, postoperative improvement can be expected, and surgical treatment should, therefore, be considered.

Immunostaining With Immunoglobulin G Subclass Antibody Cocktail for Diagnosis of Type 1 Autoimmune Pancreatitis.

BACKGROUND.: Immunoglobulin (Ig) G4-related diseases (RDs) are systemic diseases in which serum IgG4 levels are frequently elevated. They can cause diffuse or focal tumor formation, organ swelling, and tissue thickening in organs infiltrated by IgG4+ plasma cells. The diagnostic criteria for IgG4-RDs include an IgG4/IgG ratio >40%, but counting IgG+ cells can be difficult because of the weakness of IgG staining density. We hypothesized that an antibody cocktail of mixed IgG1, IgG2, IgG3, and IgG4 (AC-IgG) might give immunohistochemistry results comparable with those of IgG in IgG4-RD. METHODS.: We compared AC-IgG reactivity with IgG expression in type 1 autoimmune pancreatitis (AIP), a representative IgG4-RD. We compared immunohistochemistry results using AC-IgG and IgG-only in 10 cases of AIP. The coefficient of variation (Cv) was used to analyze differences between AC-IgG and IgG findings in AIP by 13 board-certified pathologists. RESULTS.: Although mean values for IgG+ cells did not significantly differ between AC-IgG (34.3; range = 27.4-37.1) and IgG (30.0; range = 23.0-45.6; P = .6254), Cv was lower for AC-IgG (33.4%) than for IgG (51.4%; regression equation; y[IgG] = 0.988x + 0.982; correlation coefficient = 0.907). The data showed that the results of both methods were largely consistent. CONCLUSION.: AC-IgG could replace IgG to count IgG+ cells because of its lower Cv.

Severe necrosis of the glans penis associated with calciphylaxis treated by partial penectomy.

INTRODUCTION: Calciphylaxis is characterized by marked vascular calcification and painful skin ulcers, and it has a poor prognosis. CASE PRESENTATION: The patient was a 72-year-old male. He was referred for penile pain. He had a 4-year history of dialysis therapy under a diagnosis of diabetic nephropathy. Black and yellow necrosis was observed involving the entire glans, accompanying severe pain. Computed tomography revealed marked calcification involving the thoracoabdominal aorta to iliac arteries, the dorsal artery of the penis and the corpus cavernosum, leading to a diagnosis of calciphylaxis. Penile pain gradually exacerbated and partial penectomy was performed. After surgery, penile pain promptly subsided. Pathological examination confirmed marked calcification of the microvascular wall and narrowing of the lumen. CONCLUSION: We reviewed 15 Japanese patients with calciphylaxis who had undergone penile surgery. Surgical treatment was considered to be effective at relieving penile pain, but the prognosis remained poor.

Primary central nervous system malignant melanoma with leptomeningeal melanomatosis: a case report and review of the literature.

Leptomeningeal melanomatosis is an extremely rare variant of primary central nervous system (CNS) melanoma and has a poor prognosis and no standard treatment. Primary CNS melanoma is derived from the melanocytes of the leptomeninges. Here, we describe a case of a 37-year-old male who visited our hospital due to worsening headaches. Characteristic imaging findings of this tumor type include hyper-dense lesions that are enhanced by contrast medium on computed tomography and hyper-intensity on T1-weighted magnetic resonance images and iso- to hypo-intensity on T2-weighted magnetic resonance images. Imaging of the CNS in our patient showed several lesions of this type. Pathological diagnosis and exclusion of systemic melanoma are required to confirm primary CNS malignant melanoma. Partial resection of the mass in the left temporal lobe of this patient was performed, and histological analysis showed pigmentation, melanin black-45 positivity, and BRAF mutation. Because no lesions were found outside the CNS following a thorough whole-body search, he was diagnosed with primary CNS malignant melanoma with leptomeningeal melanomatosis. He was treated with whole-brain radiation and the BRAF kinase inhibitor vemurafenib. His condition worsened, and he was given the anti-programmed cell death-1 antibody nivolumab as second-line therapy. This was also unsuccessful, and he died 5 months after treatment initiation. Further studies are needed to improve treatment and prognosis of this rare but serious disease.

Autoimmune Hepatitis Associated with Immune Thrombocytopenic Purpura.

Although autoimmune hepatitis (AIH) is frequently complicated with chronic thyroiditis or other autoimmune disorders, reports on its association with immune thrombocytopenic purpura (ITP) are scarce. We herein describe a case of AIH associated with ITP. A 75-year-old Japanese woman was admitted to our hospital due to increased aminotransferase levels and severe thrombocytopenia. Elevated serum immunoglobulin G (IgG) was detected, and tests for platelet-associated IgG and anti-nuclear antibody were positive. Following the diagnosis of AIH-associated ITP, prednisolone treatment of 0.6 mg/kg/day resulted in a decrease in the aminotransferase levels and an increased platelet count.

Incidence and prevalence of autoimmune hepatitis in the Ueda area, Japan.

AIM: Although autoimmune hepatitis (AIH) is considered to be rare in Japan, precise data on the incidence and prevalence of this disease are scarce due to the lack of a nationwide registry. We therefore conducted a study of these factors over a secondary medical care area. METHODS: We retrospectively investigated the medical records of AIH patients seen during 2004-2009 and prospectively recruited subjects from 2010 to 2014 at our hospital. We surveyed via written questionnaires to all family doctors and hospitals in our secondary medical care area of Ueda, with a population 187 205 individuals over 14 years of age. We also surveyed several core liver disease hospitals in the areas neighboring Ueda. RESULTS: Forty-eight patients with AIH were diagnosed between 2004 and 2014. AIH with histological features of acute hepatitis was increased. The average annual incidence of AIH in the area was 2.23 (age-standardized to the Japanese population). Forty-eight patients (37 patients diagnosed between 2004 and 2014, and 11 patients before 2003) were followed to the study end-point. The prevalence was 23.4 (age-standardized to the Japanese population) on 31 December 2014. After age-standardization to the World Health Organization world standard population, the incidence and prevalence of AIH decreased to 1.52 and 15.0, respectively, likely due to the high proportion of elderly patients in Japan. CONCLUSION: The incidence and prevalence of AIH in Japan may be higher than previously believed due to increased awareness among family doctors, and a rise in the diagnosis of mild or atypical AIH.

Ileocecal collision tumor composed of adenocarcinoma and primary malignant lymphoma.

Collision tumor means that two kinds of histologically distinct tumors coexist and neighbor without histological interminglement. This report describes a rare case of an ileocecal collision tumor composed of adenocarcinoma and primary malignant lymphoma. A 76-year-old woman was referred to our institute with anemia and a right lower quadrant mass. Colonoscopy revealed type 2 advanced colon cancer in the cecum accompanied by a submucosal mound neighboring this cancer, which appeared different from the usual shape of colon cancer. A barium enema study manifested the typical apple-core sign in the cecum with a smooth semicircular line appearing in the shadow of the apple-core sign. Biopsy specimens showed adenocarcinoma, so a right hemicolectomy was performed. The gross resected specimen presented a mass measuring 64 × 58 × 28 mm at the ileocecal portion. The half of this mass on the colonic side had a crater-like appearance, whereas the remaining part of the mass on the ileal side had an aspect with a smooth surface. Microscopic examination disclosed that the mass was composed of adenocarcinoma and malignant lymphoma bordering on each other and mediated by a thin layer of connective tissue. Cases of colon tumors with an unusual epithelial and submucosal appearance may be instances of collision tumors composed of cancer and malignant lymphoma.

Squamous cell carcinoma in the renal pelvis of a horseshoe kidney.

We report a rare case of squamous cell carcinoma in the renal pelvis of a horseshoe kidney. An 80-year-old woman was referred to the National Nagano Hospital for the examination of occult blood in her urine. Microscopic hematuria was found, but pyuria was not seen. Computed tomography and magnetic resonance imaging showed a mass in the left renal pelvis of the horseshoe kidney. No renal stone or hydronephrosis was found. Cytopathological examination in the voided urine specimen was positive. Left nephroureterectomy with the splitting of the isthmus of the horseshoe kidney was performed without renal pedicle clamping using a microwave tissue coagulator. No bleeding was encountered after separating the isthmus. A final pathological diagnosis of squamous cell carcinoma with a tumor thrombus was made. Lymph node metastasis had developed and rapidly progressed and the patient died of disseminated malignancy 4 months after the operation. We reviewed 24 cases of renal pelvic tumor in horseshoe kidneys previously reported in Japan. Seven cases (30%) included components of squamous cell carcinoma. The incidence is higher than that of renal pelvic tumors in the general population.

Histopathological study of the müllerian duct remnant: clarification of disease categories and terminology.

PURPOSE: We determined by histopathological studies whether there is an etiological difference in 2 distinct categories of müllerian duct remnant diseases. In addition, we clarified the nomenclature of these diseases. MATERIALS AND METHODS: We recently performed radical prostatectomy in a patient with prostate cancer associated incidentally with a so-called müllerian duct cyst in the prostatic midline. The specimen was examined by pathological and immunohistochemical testing with special attention to the relationship of the cyst and utricle. We also investigated the histology of so-called enlarged prostatic utricles or vagina masculinus extirpated from patients with severe hypospadias or intersex disorder. RESULTS: The round cyst removed with the prostate seemed to arise from the verumontanum and it contained fluid with a high concentration of prostate specific antigen. Histological and immunohistochemical examination of its lining epithelium demonstrated that cyst characteristics were identical to those of the prostatic utricle. On the other hand, pouches extirpated from patients with pediatric problems were lined by squamous epithelium. CONCLUSIONS: The so-called müllerian duct cyst appeared to originate from the prostatic utricle, and so should be termed a utricular cyst or cystic utricle. Conversely the so-called enlarged prostatic utricle should be termed a vagina masculinus or male vagina. The term müllerian duct remnant, which would include these 2 abnormalities, may usefully be replaced by the term utricular abnormalities.