HIV-associated CD8+ T-cell Skin Infiltrative Disease and EBV-associated Polymorphic B-cell Lymphoproliferative Disorder in an AIDS Patient Who Improved Dramatically with Antiretroviral Therapy Alone.

Human immunodeficiency virus (HIV)-associated CD8+ T-cell skin infiltrative disease with severe erythroderma has rarely been reported. While HIV-positive patients are prone to develop lymphoma, which is often associated with Epstein-Barr virus, polymorphic lymphoproliferative disorder is rare, accounting for <5% of cases. We herein report a 41-year-old HIV-positive man who presented with a fever, erythroderma, and lymphadenopathy and was diagnosed with the coexistence of both diseases. His condition improved significantly with continued antiretroviral therapy. This case suggests that HIV-induced immunodeficiency is central to the pathogenesis of both entities and that improvement of the immunodeficient state is an effective treatment.

Tissue processing of endoscopic ultrasound-guided fine-needle aspiration specimens from solid pancreatic lesions.

Now that tissue cores can be obtained using fine-needle biopsy (FNB) needles, the ways tissues are handled for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are changing. Direct smear, touch smear of core tissues, and centrifugation have been used for cytological examinations, and liquid-based cytology (LBC), which allows immunostaining and genetic tests that use residual samples, is emerging as an alternative. We emphasize that liquid cytology (Cytospin™ cytology and LBC) is still important, because it enables the diagnosis of pancreatic ductal adenocarcinoma (PDAC) when cancerous cells are scarce in specimens. Cell blocks are being replaced by core tissues obtained via FNB needles. Recent reports indicate that rapid on-site evaluation (ROSE) is not necessary when FNB needles are used, and macroscopic on-site evaluation is used to evaluate specimen adequacy. Macroscopic findings of specimens are helpful in the diagnostic workup and for clarifying specimen-handling methods. In addition to the red strings and white cores observed in PDAC, mixed red and white strings, gray tissues, and gelatinous tissues are observed. Gray (necrotic) tissues and gelatinous (mucus) tissues are more suitable than histology for cell block or cytological processing. Tumor cells in neuroendocrine tumors (NETs) are numerous in red strings but cannot be observed macroscopically. ROSE might thus be necessary for lesions that may be NETs. Core tissues can be used for genetic tests, such as those used for KRAS mutations and comprehensive genomic profiling. Cytological materials, including slides and LBC specimens, can also be genetic test materials.

Macroscopic qualitative evaluation of solid pancreatic lesion specimens from endoscopic ultrasound-guided fine needle aspiration/biopsies.

OBJECTIVES: To pathologically clarify the macroscopic features of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) specimens in representative pancreatic diseases and establish tissue-handling standards based on the macroscopic findings. METHODS: We gathered EUS-FNA/B specimens of cases at our institution with the final diagnoses of pancreatic ductal adenocarcinoma (PDAC, n = 172), neuroendocrine tumor (NET, n = 19), and chronic inflammatory lesion (CIL, n = 24) including autoimmune pancreatitis. We classified the specimens' macroscopic features in five categories (red strings, mixed-red-and-white strings, white cores, gray tissues, gelatinous tissues) and compared the specimens' features on cytological and histological slides. RESULTS: All five macroscopic categories were observed in variable combinations in the PDACs; red strings and white cores predominated in the NETs and CILs. White cores represented neoplastic (PDAC, NET) or lesion (CIL) tissues. Mixed-red-and-white strings were unique to PDACs and contained cancerous cells. Neoplastic cells were numerous in red strings in NETs but not the other groups. Gray and gelatinous tissues represented necrosis and mucin, respectively, and the former were almost exclusively observed in PDACs. Red strings, mixed-red-and-white strings, and white cores were suitable for histological examination, whereas gray and gelatinous tissues were suitable for cytological examination. The white cores, mixed-red-and-white strings, and gelatinous tissues may be composed of non-neoplastic tissues such as contaminated gastrointestinal epithelium. In seven PDACs, although white cores were obtained, a histological diagnosis was not established. CONCLUSIONS: Macroscopic evaluations of EUS-FNA/B can enable the identification of specimen components and a possible diagnosis. They also contribute to the selection of the optimal tissue-handling methods.

The 2022 revised diagnostic criteria for IgG4-related respiratory diseases.

In 2011, the Comprehensive Diagnostic Criteria for IgG4-related disease was published in Japan. Organ-specific diagnostic criteria based on organ-specific findings were proposed and published by each of the related societies, and the diagnostic criteria for IgG4-related respiratory disease was published in 2015. Based on the revisions to the comprehensive diagnostic criteria in 2020 and the publication of the Classification Criteria, new diagnostic criteria for IgG4-related respiratory disease are presented. Emphasis has been placed on evaluating specific pathological findings and excluding other respiratory diseases. It is mentioned in the commentary that in cases with imaging findings suggestive of interstitial pneumonia with chronic fibrosis or poor response to steroid therapy, other possible diseases should be considered.

Bilateral Lacrimal Gland Mantle Cell Lymphoma in 11-Year Follow-Up: Case Report and Review of 48 Cases With Ocular Adnexal Presentation in the Literature.

A 63-year-old woman, with 11-year history of breast cancer, showed bilateral lacrimal gland enlargement on magnetic resonance imaging. Gallium-67 scintigraphy, as the standard at that time in 2004, demonstrated abnormally high uptake only in bilateral lacrimal glands. The lacrimal glands were extirpated and the pathological diagnosis was mantle cell lymphoma (MCL). She underwent bilateral orbital radiation, based on no uptake of gallium-67 in other sites of the body. In a month, bone marrow biopsy revealed the infiltration with MCL, positive for cyclin D1. She showed hepatic lymphadenopathy and splenomegaly, and so received 2 cycles of alternating Hyper-CVAD therapy and high-dose methotrexate with cytarabine, combined with rituximab, in 2 months, leading to complete remission. She underwent autologous peripheral blood stem cell transplantation and was well until the age of 68 years when she showed a recurrent intratracheal submucosal lesion of lymphoma and underwent one course of reduced-dose CHOP combined with rituximab. Next year, the left rib resection revealed the metastasis of breast adenocarcinoma, leading to daily oral letrozole. Further 2 years later, computed tomographic scan demonstrated multiple submucosal nodular lesions in the trachea and bronchi, together with cervical and supraclavicular lymphadenopathy, and intratracheal lesion biopsy and bone marrow biopsy proved the involvement with MCL. She underwent 2 courses of bendamustine and rituximab, resulting in complete remission but died of metastatic breast cancer at the age of 74 years. Clinical features in 48 previous cases with ocular adnexal MCL in the literature were summarized in this study.

A case of immunoglobulin G4-related retroperitoneal fibrosis and hypophysitis with antecedent respiratory disease followed by spontaneous remission and recurrence.

A 65-year-old man presented with apparent bronchopneumonia. After treatment with antibiotics, he showed eosinophilia. Computed tomography (CT) imaging revealed bilateral consolidation, ground-glass opacities with nodular consolidations, and pleural effusion. Lung biopsy showed organising pneumonia with lymphoplasmacytic infiltration in the alveolar septa and in the thickened pleura and interlobular septa. All pulmonary abnormalities spontaneously went into remission within 12 months. At 73 years old, a follow-up CT scan revealed small nodules in both lungs and the review of the head CT scan showed thickening of the pituitary stalk in studying prolonged headache. Two years later, he visited the hospital complaining of severe oedema on the lower extremities with high serum immunoglobulin (Ig)G4 186 mg/dl. A whole-body CT scan showed retroperitoneal mass surrounding aortic bifurcation and compressing inferior vena cava, pituitary stalk thickening and gland swelling, and enlarged pulmonary nodules. Anterior pituitary stimulation tests showed central hypothyroidism, central hypogonadism, and adult growth hormone deficiency with partial primary hypoadrenocorticism. Retroperitoneal mass biopsy showed storiform fibrosis and obliterative phlebitis with marked lymphoplasmacytic infiltration with moderate IgG4-positivity. Immunostaining of the former lung specimen revealed dense interstitial infiltration of IgG4-positive cells. These findings indicated metachronous development of IgG4-related disease in lung, hypophysis, and retroperitoneum, according to the recent comprehensive diagnostic criteria of IgG4-related disease. Glucocorticoid therapy ameliorated oedema, on the other hand, unmasked partial diabetes insipidus at the initial dose of the treatment. Hypothyroidism and retroperitoneal mass regressed at 6 months of the treatment. This case warns us that long-term follow-up from prodromal to remission is necessary for the treatment of IgG4-related disease.

Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer.

The extent of tumor spread influences on the clinical outcome, and which determine T stage of colorectal cancer. However, pathologic discrimination between pT3 and pT4a in the eighth edition of the American Joint Committee on Cancer (AJCC)-TNM stage is subjective, and more objective discrimination method for deeply invasive advanced colon cancer is mandatory for standardized patient management. Peritoneal elastic laminal invasion (ELI) detected using elastic staining may increase the objective discrimination of deeply invasive advanced colon cancer. In this study, we constructed ELI study group to investigate feasibility, objectivity, and prognostic utility of ELI. Furthermore, pT classification using ELI was investigated based on these data. At first, concordance study investigated objectivity using 60 pT3 and pT4a colon cancers. Simultaneously, a multi-institutional retrospective study was performed to assess ELI's prognostic utility in 1202 colon cancer cases from 6 institutions. In the concordance study, objectivity, represented by κ, was higher in the ELI assessment than in pT classification. In the multi-institutional retrospective study, elastic staining revealed that ELI was a strong prognostic factor. The clinical outcome of pT3 cases with ELI was significantly and consistently worse than that of those without ELI. pT classification into pT3 without ELI, pT3 with ELI, and pT4a was an independent prognostic factor. In this study, we revealed that ELI is an objective method for discriminating deeply invasive advanced colon cancer. Based on its feasibility, objectivity, and prognostic utility, ELI can subdivide pT3 lesions into pT3a (without ELI) and pT3b (with ELI).

Long-term outcomes of drug-induced autoimmune-like hepatitis after pulse steroid therapy.

AIM: Pulse steroid therapy occasionally causes drug-induced autoimmune-like hepatitis (DI-ALH), but the long-term outcome of treated patients is not well known. In this study, we investigated the long-term outcomes of DI-ALH due to pulse steroid therapy. METHODS: We retrospectively reviewed the medical records of 405 patients treated with pulse high-dose methylprednisolone in Kurashiki Central Hospital. The frequency and clinicopathological characteristics of acute liver injury that occurred within 3 months after the therapy were analyzed. The diagnosis of DI-ALH was made according to the revised international autoimmune hepatitis group criteria. RESULTS: Among the 405 patients treated with methylprednisolone, 61 (15.1%) had acute liver injury after the pulse steroid therapy, and DI-ALH was diagnosed in five patients (1.2%). Absence of oral prednisolone tapering after the pulse steroid therapy was a significant risk factor for the subsequent development of DI-ALH (odds ratio 11.9; p = 0.017). One patient was treated with 3 days of intravenous methylprednisolone followed by oral prednisolone. Two patients were treated with glycyrrhizin followed by oral prednisolone due to ineffectiveness of glycyrrhizin. Remission was achieved with glycyrrhizin alone, and spontaneous remission without drug therapy occurred in one patient each. During the median follow-up period of 34 months, no relapse was evident in all the patients without maintenance therapy. CONCLUSIONS: Pulse steroid therapy can cause DI-ALH, especially when subsequent prednisolone is not tapered. Prednisolone is effective for DI-ALH due to pulse steroid therapy, and can be safely withdrawn once remission is achieved.

A case of pancreatic ductal adenocarcinoma concomitant with IgG4-related disease in the pancreas and the stomach.

A 75-year-old Japanese woman visited a hospital with a stomachache. The patient was diagnosed with localized mild acute pancreatitis. Blood tests revealed elevated serum IgG4 levels. Contrast-enhanced computed tomography showed a hypovascular mass, 3 cm in size, in the pancreatic body with dilation of the upstream duct. Additionally, it showed another tumorous lesion of 10 mm in size in the anterior wall of the stomach, and endoscopic examination confirmed a submucosal tumor (SMT) sized 10 mm in the anterior wall of the stomach. Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) of the pancreas revealed an adenocarcinoma concomitant with marked IgG4-positive cell infiltration. Hence, distal pancreatectomy with local gastrectomy was performed, and the final diagnosis was concluded as pancreatic ductal adenocarcinoma (PDAC) complicated by IgG4-related diseases (IgG4-RD) in the pancreas and stomach. IgG4-RD of the digestive tract is exceedingly rare. The correlation between PDAC and autoimmune pancreatitis or malignancy and IgG4-RD is controversial. However, the clinical course and histopathological examination, in this case, provide valuable suggestive findings for further discussion.

Primary sclerosing cholangitis with partial steroid responsiveness: a case report.

A 69-year-old woman suspected to have IgG4-related sclerosing cholangitis causing bile duct stenosis was transferred from another hospital after diarrhea, eosinophilia, and eosinophilic infiltration were detected and prednisolone was prescribed. Additional biliary imaging suggested primary sclerosing cholangitis, but the IgG4 level and inferior bile duct stenosis were alleviated by steroid therapy, suggesting IgG4-related sclerosing cholangitis. Therefore, prednisolone was continued. Bile duct biopsy findings suggesting adenocarcinoma led to a diagnosis of pancreatoduodenectomy. The latter specimen only displayed evidence of primary sclerosing cholangitis, and prednisolone was discontinued. Intractable cholangitis necessitated left hepatectomy, after which serum alkaline phosphatase levels increased and eosinophilic colitis recurred. The reintroduction of prednisolone effectively managed the diarrhea but only temporarily reversed the alkaline phosphatase elevation. When histologic sections from resection specimens were compared, the hepatectomy specimen exhibited greater eosinophil infiltration than the earlier pancreatoduodenectomy specimen, suggesting eosinophilic cholangiopathy superimposed on primary sclerosing cholangitis.

Immunoglobulin G4-related Hepatopathy after COVID-19 Vaccination.

An 84-year-old woman with IgG4-related disease presented with jaundice and liver dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Serum IgG4 levels were elevated. Diagnostic imaging showed no stenotic lesions in the bile ducts. A liver biopsy was performed because of the enlarged liver. Infiltration of IgG4-positive plasma cells, which accounted for approximately 74% of total plasma cells, was found in the portal area, but there was no evidence of periportal hepatitis, and inflammatory cell infiltration into the lobular space was minimal. IgG4-related hepatopathy was diagnosed. The patient achieved spontaneous remission with no treatment and only follow-up and remains under observation at the time of writing.

Corticosteroid-refractory autoimmune hepatitis after COVID-19 vaccination: a case report and literature review.

Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination.

Multiple hemangiomas (hepatic small vessel neoplasia) in the liver with Budd-Chiari syndrome.

Hepatic small vessel neoplasia (HSVN) is a recently recognized hemangioma of the liver with uncertain malignant potential. Almost all the patients are asymptomatic. Budd-Chiari syndrome (BCS) is a rare disorder characterized by noncardiogenic hepatic venous outflow obstruction. Benign hepatocellular nodules have been acknowledged for a long time in the liver with the chronic BCS. However, there has been no case report of BCS associated with HSVN. The patient was diagnosed with BCS 13 years ago. The imaging test initially displayed multiple hepatic nodules that were suspected of benign hepatocellular nodules. They gradually increased in size and number in the course of the disease. At an autopsy, these nodules were confirmed to be multifocal HSVN. The tumor of the present case could not be proved to have GNAQ and GNQ14 mutations. We describe the case focusing on the chronological imaging changes and discuss on the relationship between BCS and HSVN.

A case of type 2 autoimmune pancreatitis with spontaneous remission.

A 70-year-old man with epigastric pain was referred to our hospital. Computed tomography and magnetic resonance imaging showed the diffusely enlarged pancreas compared to his normal pancreas 6 months prior to presentation. Serum levels of IgG4 and amylase were normal, while C-reactive protein was slightly elevated. Endoscopic ultrasound-guided fine-needle biopsy of the pancreas revealed acinar-ductal metaplasia with neutrophil infiltration and without infiltration of IgG4-positive plasma cells. After the clinical diagnosis of type 2 autoimmune pancreatitis (AIP), his symptoms spontaneously improved without steroid therapy. Three months later, radiological findings showed improved pancreas size and serological findings. The pathological diagnosis of type 2 AIP using endoscopic ultrasound-guided fine-needle biopsy is challenging, particularly for proving granulocyte epithelial lesions. This was a valuable type 2 AIP case in which the images before, at the time of onset, and at the time of spontaneous remission were evaluated.

Concomitant Pancreatic Ductal Adenocarcinoma and Type 1 Autoimmune Pancreatitis: A Potential Issue in the Diagnosis of Carcinoma by Endoscopic Ultrasound-guided Fine-needle Biopsy.

We herein report a 64-year-old man with concomitant pancreatic ductal adenocarcinoma (PDAC) and type 1 autoimmune pancreatitis (AIP). An endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) from the pancreatic head mass revealed level 2 histology of AIP and atypical glands. We diagnosed definitive focal AIP using the clinical diagnostic criteria. Computed tomography revealed that the pancreatic mass had not been reduced by steroid therapy. Surgery was performed after a histological PDAC diagnosis was made via a transpapillary biliary biopsy. The resected specimen revealed PDAC associated with AIP. It is important to consider the cooccurrence of PDAC and AIP even if the histological diagnosis via an EUS-FNB is AIP.

A Tumefactive Fibroinflammatory Lesion of the Head and Neck Mimicking Immunoglobulin G4-related Disease.

A 67-year-old woman with a 5-year history of recurrent swollen eyelids and epistaxis, diagnosed as immunoglobulin G4-related diseases (IgG4-RD) based on hyper-IgG4-emia and IgG4-positive cell infiltration to the lesion, was referred to our department due to recurrent symptoms despite corticosteroid therapies. Computed tomography revealed an osteoclastic sinus mass with prominent neutrophil infiltration and necrosis that was incompatible with IgG4-RD histopathologically. Finally, she was diagnosed with a tumefactive fibroinflammatory lesion (TFIL) of the head and neck and treated with high-dose corticosteroids. Physicians should remember that TFIL can mimic IgG4-RD in the head and neck region with prominent neutrophil infiltration and necrosis.

A Case of Immunoglobulin G4-Related Gastrointestinal Disease Diagnosed From Persistent Diarrhea and Abdominal Pain.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by the infiltration of IgG4-positive plasma cells and fibrosis in organs throughout the body. IgG4-RD involvement in the gastrointestinal (GI) tract (IgG4-related GI disease; IgG4-GID) is rare, and the disease concept remains unclear. Generally, IgG4-GID has been reported with morphological changes, including ulcers, strictures, and submucosal tumors. Here, we report a case of IgG4-GID with persistent diarrhea and abdominal pain in which typical endoscopic findings were absent. This case suggests the unidentified clinical features of IgG4-GID.

Diffuse large B-cell lymphoma in the course of systemic sarcoidosis: A case report and review of 30 Japanese patients with sarcoidosis-lymphoma syndrome.

We report a patient with sarcoidosis who developed diffuse large B-cell lymphoma. A 71-year-old woman with persistent cough was diagnosed pathologically with sarcoidosis by resection of the right upper lung lobe with a nodule after an unsuccessful attempt of transbronchial needle aspiration for mediastinal lymphadenopathy. She was referred for an eye examination and found to have spotty retinal degeneration on the lower fundi of both eyes, together with residual macular edema and vitreous opacity in the left eye. At 76 years, she underwent cataract surgery and vitrectomy to gain a visual acuity of 0.6 in the left eye. At 77 years, she developed a cough and fever, and showed leukopenia and thrombocytopenia. Computed tomography showed multiple small nodular lesions in both lungs, and bilateral hilar, mediastinal, and hepatic lymphadenopathy. Fluorodeoxyglucose positron emission tomography demonstrated high uptake in the liver, spleen, pancreatic head, and lymph nodes. Bone marrow biopsy was intact, but liver biopsy revealed anomalous large lymphoid cells in the sinusoids which were positive for CD20 and showed a high Ki-67 index, leading to the diagnosis of diffuse large B-cell lymphoma. Chemotherapy with 8 courses of THP-COP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with rituximab, followed by intrathecal injection of methotrexate, cytarabine, and dexamethasone, resulted in complete remission. She maintained complete remission for 10 years until 88 years old at present. The literature review found 30 patients, including this case, who developed lymphoma in the course of sarcoidosis. A novel pathological diagnosis is required in the setting of acute symptomatic changes and novel lesions on imaging in patients with sarcoidosis.

Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients.

BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.