ABSTRACT A 74‐year‐old man presented with abdominal pain. Preoperative evaluation for small bowel perforation revealed a 74‐mm tumour shadow obstructing the right lower lobe bronchus. Endobronchial biopsy from the truncus intermedius was diagnostic of squamous cell carcinoma (SCC). Pathological findings in the small intestine were consistent with SCC. Based on other radiological findings, the patient was diagnosed with stage IVB (cT4N3M1c) lung SCC (LUSC). Serum amylase levels were elevated at 1693 U/L (pancreatic amylase 184 U/L) prior to treatment. AMY1 (2D4) immunohistochemistry was positive, confirming amylase‐producing LUSC, a rarely reported entity. Amylase levels decreased to 203 U/L following combination therapy with carboplatin, nab‐paclitaxel and pembrolizumab. The patient had no symptoms or signs of pancreatic or salivary gland disease. To our knowledge, this is the first reported case of LUSC with both histological evidence of amylase production and hyperamylasemia. This case provides new evidence that LUSC can produce amylase and cause hyperamylasemia.

Acute generalized exanthematous pustulosis (AGEP) is a severe skin inflammation characterized by the sudden onset of numerous sterile, non-follicular pustules on an erythematous and edematous background, usually associated with fever. AGEP is commonly triggered by medications such as antibiotics. However, an association between AGEP and viral infections has also been reported recently. We report a case of a 70-year-old man who developed AGEP following the intake of an over-the-counter cold medicine in the context of herpes simplex virus (HSV) reactivation. Furthermore, we review three cases of AGEP associated with HSV infection. This report suggests HSV reactivation as a potential trigger for AGEP, emphasizing the need for caution when administering drugs to patients with HSV infection.

Acquired reactive perforating dermatosis (ARPD) is characterized by its onset after the age of 18 years, umbilicated papules or nodules with a central keratotic plug, and the presence of necrotic collagen tissue within an epithelial crater. ARPD is strongly associated with systemic diseases such as diabetes mellitus (DM) and chronic renal failure, which may contribute to ARPD through factors including microcirculatory disturbances and the deposition of metabolic byproducts, including advanced glycation end-products and calcium. Here, we report a case of ARPD that improved following DM treatment and catheter-based interventions for peripheral artery disease (PAD). The eruptions on the upper limbs significantly improved with DM management. On the other hand, lesions on the lower limbs showed marked improvement after the enhancement in arterial blood flow due to catheter surgeries, along with DM treatment. Although a few reports of ARPD improving with DM management exist, our case underscores the importance of adequate DM control in ARPD management. The inability to perform the biopsy of the lesions on the lower limbs is our limitation; however, these lesions, similar to those on the upper limbs, presented with a central keratotic plug and re-epithelialized without forming ulcers or erosions, suggesting they were also related to ARPD. To date, there has been little discussion on the relationship between blood flow impairment in major vessels and ARPD. However, hypertension and venous circulatory dysfunctions are considered to lead to ARPD, raising the possibility that PAD-induced microvascular disturbances might have facilitated lesion formation in the present case. Further accumulation of cases and research is needed to clarify the relationship between blood flow impairment in major vessels and ARPD.

Myxedema coma, a life-threatening complication of severe hypothyroidism, is associated with high mortality. Detailed autopsy findings from multiple organs in myxedema coma are rarely reported. We present the autopsy findings of an 82-year-old man with hypothyroidism who developed myxedema coma despite levothyroxine treatment. The patient had been under the added stress of trauma and cold exposure before developing a myxedema coma. He exhibited severe hypothermia, hypotension, and reduced thyroid hormone levels. Despite intensive treatment, he died six days after admission. Autopsy revealed pericardial and pleural effusions, and histological evidence of edematous adipose tissue infiltration containing mucopolysaccharides in multiple organs, including the heart, thyroid, pancreas, and kidneys. This case highlights that both trauma and cold exposure can serve as critical triggers for myxedema coma, underscoring the importance of proactive management in hypothyroid patients at risk. These risk factors should be carefully considered in clinical practice to prevent severe complications. Our autopsy findings provide the first evidence that myxedema can manifest not only in subcutaneous tissue but also in internal organs, expanding the understanding of its pathophysiology. These insights may contribute to improved prevention and management of myxedema coma, offering a deeper understanding of this life-threatening condition.

Placental transmogrification of the lung (PTL) is a rare, bullous lung disease with unknown pathogenesis. This is a case of PTL in AKT1-related Proteus syndrome. This overgrowth spectrum disorder was caused by a mosaic AKT1 pathogenic variant. https://bit.ly/4h6S6AG.

A 42-year-old man visited our hospital complaining of secondary infertility. An abdominal ultrasonography screening incidentally revealed a protruding lesion in the bladder. As the lesion extended from the prostatic urethra and bladder neck, there was a possibility of ejaculation dysfunction after resection of the lesion. Therefore, with the patient's informed consent, sperm cryopreservation was conducted for fertility preservation, and subsequently histological examination was performed by partial transurethral resection of bladder tumor. The pathological findings were proliferative cystitis including all three subtypes (glandularis, cystica, and papillary). Cyclooxygenase-2 immunostaining was positive in cytoplasm; weakly positive in cystic and papillary lesions, and strongly positive in glandular lesions. According to a literature review of massive proliferative cystitis, the patient was the 77th case in Japan. Novel postoperative immunological pharmacotherapies with cyclooxygenase-2 inhibitors have been introduced in recent years.

Yoshihito Mima,1,2 Tsutomu Ohtsuka,2 Ippei Ebato,2 Yukihiro Nakata,2 Yoshimasa Nakazato,3 Yuta Norimatsu4 1Department of Dermatology, Tokyo Metropolitan Police Hospital, Tokyo, Japan; 2Department of Dermatology, International University of Health and Welfare Hospital, Tochigi, Japan; 3Department of Diagnostic Pathology, International University of Health and Welfare Hospital, Tochigi, Japan; 4Department of Dermatology, International University of Health and Welfare, Narita Hospital, Chiba, JapanCorrespondence: Yoshihito Mima, Department of Dermatology, Tokyo Metropolitan Police Hospital, 4-22-1 Nakano, Nakano-ku, Tokyo, 164-8541, Japan, Tel +81-03-5343-5611, Fax +81-03-5343-5612, Email yoshihito11.mima@gmail.comAbstract: Urticarial vasculitis is characterized by persistent urticarial lesions lasting over 24 h. Urticarial vasculitis is often triggered by medications, infections, and autoimmune disorders. However, vaccinations against viral and bacterial pathogens have recently been documented to induce urticarial vasculitis. We describe the case of a 67-year-old woman who was presented with an extensive erythematous and purpuric rash without systemic symptoms 3 days after an influenza vaccination. She was diagnosed with normocomplementemic urticarial vasculitis based on clinical findings, normal complement levels, and histopathological findings of leukocytoclastic vasculitis. After receiving oral histamines, she showed complete resolution 3 months after receiving the influenza vaccination. Although vaccination-associated vasculitis is common, urticarial vasculitis following vaccinations is rare. We reviewed 13 cases of urticarial vasculitis following a wide range of vaccines, including those against Bacillus Calmette–Guérin, serogroup B meningococcus, influenza, and coronavirus disease. We conducted a comprehensive review of various aspects, including age, sex, past medical history, type of vaccination, number of vaccinations, onset time, cutaneous symptoms, place of eruption, systemic symptoms, laboratory disorders, treatment period, and treatment of urticarial vasculitis. Two patients developed hypocomplementemic urticarial vasculitis after vaccination, and both experienced systemic symptoms such as arthralgia and fever. In this review, no significant differences were found in the data, which may be attributed to the small number of cases. The mechanisms underlying the induction of urticarial vasculitis by vaccines remain unknown; however, in addition to immune complex deposition and complement activation due to vaccine components, molecular mimicry may trigger urticarial vasculitis by producing vaccine-derived pathogenic antigen antibodies. This case study emphasizes the need for heightened awareness and further investigation of urticarial vasculitis as a rare adverse effect of vaccination.Keywords: vaccination, vasculitis, anticardiolipin antibody, molecular mimicry

Immune checkpoint inhibitors (ICIs) activate T cells, causing immune-related adverse events (irAEs). Skin manifestations are common among irAEs, but ICI-associated bullous pemphigoid (BP) is rare. Inhibiting programmed death (PD)-1 signaling, in addition to causing epitope spreading, may disrupt B and T cell balance, causing excessive autoantibody production against the skin’s basement membrane, leading to BP. A 70-year-old woman developed late-onset multi-organ irAEs, including diarrhea, thyroid dysfunction, and BP, while receiving pembrolizumab, a PD-1 inhibitor. This highlights the long-term risk of irAEs, which can occur 2–3 years after starting ICIs. In cases of multi-organ irAE, C-reactive protein levels and neutrophil/lymphocyte ratio are often low. These characteristics were observed in our case. Few papers address multiple organ involvement, highlighting the need to consider irAEs in a multi-organ context. While it is known that drug-induced skin reactions worsen as blood eosinophil counts increase, in our case, the eosinophil count remained normal, suggesting that ICI-associated BP might have been controlled without discontinuing the ICI and through tapering of low-dose oral prednisone treatment. Additionally, in this case, significant CD4-positive T cell infiltration was observed in the immunostaining examination of the blisters, indicating that severe CD4-positive T cell infiltration induced by the ICI might have led to multi-organ involvement, including severe diarrhea. Few reports focus on blood eosinophil counts in BP cases or discuss CD4 and CD8 immunostaining in BP cases. Therefore, future research should explore the relationship between blood eosinophil counts, immunostaining results, and the prognosis of irAEs, including BP, in treatment courses.

Immune checkpoints are mechanisms that allow cancer cells to evade immune surveillance and avoid destruction by the body’s immune system. Tumor cells exploit immune checkpoint proteins to inhibit T cell activation, thus enhancing their resistance to immune attacks. Immune checkpoint inhibitors, like nivolumab, work by reactivating these suppressed T cells to target cancer cells. However, this reactivation can disrupt immune balance and cause immune-related adverse events. This report presents a rare case of prurigo nodularis that developed six months after administering nivolumab for lung adenocarcinoma. While immune-related adverse events are commonly linked to T helper-1- or T helper-17-type inflammations, T helper-2-type inflammatory reactions, as observed in our case, are unusual. The PD-1–PD-L1 pathway is typically associated with T helper-1 and 17 responses, whereas the PD-1–PD-L2 pathway is linked to T helper-2 responses. Inhibition of PD-1 can enhance PD-L1 functions, potentially shifting the immune response towards T helper-1 and 17 types, but it may also influence T helper-2-type inflammation. This study reviews T helper-2-type inflammatory diseases emerging from immune checkpoint inhibitor treatment, highlighting the novelty of our findings.

Introduction: Gastric cancer has been reported to occur with mild to moderate mucosal atrophy, particularly after the eradication of Helicobacter pylori ( HP ) more than 10 years previously. However, no conclusion has been reached on how many years of esophagogastroduodenoscopy should be performed after HP eradication. Presentation of case: This was a case of gastric carcinoma of the fundic gland type (GCFGT) 32 years after the eradication of HP , which is the longest posteradication period reported. A 62-year-old male patient was diagnosed with GCFGT after HP eradication and regular esophagogastroduodenoscopy, which revealed a white raised lesion on the anterior wall of the upper part of the body. Endoscopic submucosal dissection was performed for GCFGT, and the vertical and horizontal margins were negative. Clinical discussion: In this case, HP was eradicated in 1990, and GCFGT developed 32 years later. To the best of our knowledge, this is the longest case in which gastric cancer appeared after HP eradication. HP eradication therapy for a duodenal ulcer was first reported in 1990, supporting that this is the longest case. Conclusions: This is the first case of gastric cancer more than 20 years after the eradication of HP . The endoscopic findings of this case are typical of GCFGT and may be useful when encountering such cases in the future. Therefore, the risk of gastric cancer should be considered for an extended period even after the eradication of HP , and regular esophagogastroduodenoscopy is recommended even after the eradication of HP .

693 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of anti-Nectin-4 antibody and is approved for metastatic urothelial cancer. Predictors of therapeutic benefit of EV have not been established since nectin-4 expression varies widely with the course of treatment. ATP Binding Cassette (ABC) transporters which export the administered anti-cancer drugs out of the cells have been postulated as one of the mechanisms of therapeutic resistance to EV. In this study, we evaluated the expression of Nectin-4 and ABC transporters in primary biopsy tissues, primary radical resection tissues, and metastatic sites from urothelial cancer patients and evaluated their association with prognosis after EV therapy. Methods: We studied 16 patients who received enfortumab vedotin for metastatic urothelial cancer. Biopsy of primary tissue, radical surgery of primary tumor, and resection of metastatic sites was performed in 16, 7, and 4 patients, respectively. In these specimens, the expression of nectin-4 and ABC transporters was evaluated by immunostaining. Among ABC transporters, we evaluated MDR1 (ABCB1), MRP1 (ABCC1), and BCRP (ABCG2) since they have been reported to be associated with anticancer drug resistance. Staining intensity on the cell membrane was classified into 0 to 3 according to the evaluation criteria of HER2. We investigated the relationship between the expression of nectin-4 and ABC transporters and survival after EV therapy. Results: Nectin-4 was positive in all patients (score 3 in 12 patients, score 1 in 4 patients) in primary biopsy. All patients tested negative for MDR1. MRP1 was positive in 11 (score 2 in 2 patients and score 1 in 9 patients), and BCRP was positive in 14 (score 2 in 10 patients, score 1 in 4 patients). Nectin-4 expression decreased in radical surgery tissues and metastatic sites. On the other hand, ABC transporter expression remained unchanged or rather increased in radical surgery tissues and metastatic sites (Table). Patients with both MRP1 and BCRP expression in the primary biopsy specimen (n=8) had significantly worse PFS and OS after EV therapy while nectin-4 expression in the primary biopsy specimen was not associated with survival. Conclusions: Patients with ABC transporter expression had a poor prognosis after EV therapy, although nectin-4 expression in primary biopsies was not associated with prognosis. Nectin-4 expression tended to decrease, while the ABC transporter remained unchanged or enhanced as the disease progressed. [Table: see text]

A 76-year-old woman was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma by upper gastrointestinal endoscopy. She underwent further investigation for concomitant bilateral pleural effusions and right pulmonary consolidation. MALT lymphoma with the t(11; 18)(q21; q21) translocation and API2-MALT1 were detected in pleural fluid. Lymphoma was not histopathologically diagnosed by lung biopsies, but the same translocation was identified in bronchial lavage. MALT lymphoma is often difficult to diagnose by bronchoscopy because of only mild dysplasia. However, present report on using chromosomal translocation analysis from bronchial lavage indicates that such testing may serve as a useful diagnostic adjunct in MALT lymphoma with lung involvement.

A 53-year-old woman undergoing combination therapy with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) inhibitors for advanced lung cancer with brain metastases developed pustules and punctate purpura on both lower extremities. Histopathological examination revealed neutrophilic infiltration around the hair follicles and erythrocyte extravasation in the perivascular regions near the hair roots, leading to a diagnosis of purpuric papulopustular eruptions. The rash improved with oral doxycycline (100 mg/day) and topical corticosteroids. This case demonstrates that extensive purpuric drug eruptions without symptoms of vasculitis can be effectively managed with oral antibiotics, without the need for chemotherapy discontinuation or systemic corticosteroids. EGFR inhibitors can induce purpuric papulopustular eruptions through follicular occlusion and damage to vascular endothelial cells via inflammatory cells. In our case, the treatment duration was longer than previously reported, suggesting that VEGFR inhibitors delay wound healing and endothelial cell repair, potentially contributing to the development of purpuric papulopustular eruptions. As combination therapy with EGFR and VEGFR inhibitors was only introduced in 2022, to the best of our knowledge, the present case is the first of purpuric papulopustular eruptions occurring during this treatment regimen.

Kumazawa, Mariko MD*; Arakawa, Hiroaki MD*; Nakajima, Takahiro MD†; Chida, Masayuki MD†; Nakazato, Yoshimasa MD‡ Author Information

Metastasis from small-cell lung cancer to the colon is very rare. A 74-year-old man without respiratory or abdominal symptoms underwent a follow-up lower gastrointestinal endoscopy after a polypectomy. He was diagnosed with a 5 mm IIa non-hyperplastic polyp in the cecum and underwent a cold snare polypectomy. The histopathological findings confirmed the diagnosis of small cell carcinoma. The tumor was positive in the deep margins of the submucosal layer. Subsequent systemic examination revealed a mass in the lower lobe of the left lung. Thus, the tumor in the cecum was determined to be a colorectal metastasis from primary small-cell carcinoma of the lung. Metastasis to the colon was diagnosed as small-cell lung cancer based on local positivity for thyroid transcription factor-1 and morphologic and immunochemical features. To our best knowledge, this is the first report of colon metastasis from small cell carcinoma identified by endoscopic treatment.

A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumors have recently attracted attention. The patient, a 75-year-old woman with epigastric pain and nausea, was found to have a type 2 tumor of the duodenum, which was diagnosed on biopsy as a poorly differentiated carcinoma. A pancreaticoduodenectomy specimen showed a well-defined 50 × 48 mm tumor in the duodenal bulb, which was morphologically composed of glandular, sheet-like, and pleomorphic components. The glandular component was a tubular adenocarcinoma, showing a MUC5AC-positive gastric type. The sheet-like component consisted of homogenous tumor cells, with chromogranin A and synaptophysin diffusely positive, and a Ki-67 index of 72.8%. The pleomorphic component was diverse and prominent atypical tumor cells proliferated, focally positive for chromogranin A, diffusely positive for synaptophysin, and the Ki-67 index was 67.1%. The sheet-like and pleomorphic components were considered NEC, showing aberrant expression of p53, retinoblastoma, and p16. Notably, all three components were deficient in MLH1 and PMS2. We diagnosed a non-ampullary duodenal MANEC with MMR deficiency. This tumor has a unique morphology and immunohistochemical profile, and is valuable for clarifying the tumorigenesis mechanism of a non-ampullary duodenal MANEC.

Atypical lymphoproliferative disorders (LPDs) related with autoimmune disease (AID) show marked clinicopathological diversity, which are defined as three distinct clinicopathological subtypes such as those resembling Castleman disease (CD), atypical paracortical hyperplasia with lymphoid follicles (APHLF), and atypical lymphoplasmacytic and immunoblastic proliferation (ALPIB). We studied excisional biopsy specimens from 31 patients with atypical LPDs associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren syndrome (SjS). The lesions in these 31 cases were classified into 6 (19.4%) cases resembling CD, 14 (45.2%) cases of APHLF, and 11 (35.5%) cases of ALPIB. Five cases (83.3%) resembling CD were in the active stage with systemic symptoms and multicentric lymphadenopathy. Thirteen cases (92.9%) of APHLF showed systemic symptoms, multicentric lymphadenopathy and abnormal laboratory findings. Histologic findings for cases resembling CD were rare in patients with RA and SjS. In AID patients, histologic findings for cases resembling CD or APHLF findings correlated with disease activity and multicentric lymphadenopathy. Six cases (54.5%) of ALPIB were in the active phase with systemic symptoms and multicentric lymphadenopathy. ALPIB tended to be unrelated to AID activity, especially in the majority of patients with no abnormal laboratory findings. Atypical LPDs associated with AID is a group of diseases that may be overdiagnosed and overtreated. The diagnosis of atypical LPDs associated with AID requires an understanding of the histological findings as well as a comprehensive assessment of the presence of systemic symptoms, the distribution of lymphadenopathy, and abnormal laboratory findings.

Cryptococcal granulomatous prostatitis is extremely rare, and there have been few reports of its diagnosis by prostate needle biopsy. The patient, an 81-year-old man, was receiving immunosuppressive treatment for rheumatoid arthritis. He had an oropharyngeal ulcer, and it was diagnosed alongside a methotrexate-related diffuse large B-cell lymphoma. A systemic imaging examination revealed a prostatic tumor-like mass clinically suspected to be prostatic cancer, and a needle biopsy was performed. The biopsy specimen showed various types of inflammatory cell infiltration, and suppurative granuloma and caseous granuloma were observed. Both granulomas showed multiple round and oval organisms that were revealed with Grocott methenamine silver staining. Acid-fast bacilli were not detected by Ziehl-Neelsen staining. We histologically diagnosed granulomatous prostatitis caused by Cryptococcus infection. Caseous granulomas often develop in the prostate after bacillus Calmette-Guerin immunotherapy for bladder cancer, although the possibility of cryptococcal granulomatous prostatitis should also be considered.