Disseminated nontuberculous mycobacteriosis and fungemia after second delivery in a patient with MonoMAC syndrome/GATA2 mutation: a case report.

BACKGROUND: Heterozygous mutations in the transcription factor GATA2 result in a wide spectrum of clinical phenotypes, including monocytopenia and Mycobacterium avium complex (MAC) infection (MonoMAC) syndrome. Patients with MonoMAC syndrome typically are infected by disseminated nontuberculous mycobacteria, fungi, and human papillomavirus, exhibit pulmonary alveolar proteinosis during late adolescence or early adulthood, and manifest with decreased content of dendritic cells (DCs), monocytes, and B and natural killer (NK) cells. CASE PRESENTATION: A 39-year-old woman was diagnosed with MonoMAC syndrome postmortem. Although she was followed up based on the symptoms associated with leukocytopenia that was disguised as sarcoidosis with bone marrow involvement, she developed disseminated nontuberculous mycobacterial infection, fungemia, and MonoMAC syndrome after childbirth. Genetic testing revealed a heterozygous missense mutation in GATA2 (c.1114G > A, p.A372T). Immunohistochemistry and flow cytometry showed the disappearance of DCs and decreased frequency of NK cells in the bone marrow, respectively, after childbirth. CONCLUSIONS: To the best of our knowledge, this is the first study reporting that MonoMAC syndrome can be exacerbated after childbirth, and that immunohistochemistry of bone marrow sections to detect decreased DC content is useful to suspect MonoMAC syndrome.

Pulmonary infarction caused by sarcoidosis vascular involvement: A case report.

Sarcoidosis is a systemic granulomatous disease. In pulmonary sarcoidosis, granulomatous vascular involvement is a common feature that occurs in all types of vessels, including large elastic arteries to venules, but sarcoidosis complicated with pulmonary infarction has not been reported. We report a case of a 60 years old female, who was operated on a clinical diagnosis of lung cancer, and histological examination revealed a pulmonary infarction and sarcoidosis. In the pulmonary elastic arteries, granulomas infiltrated the adventitia and media, and caused elastic fiber collapse and destruction. Arterial occlusion by granulomas was observed in the edge of the infarcted area. It was considered that the arterial sarcoidosis granuloma involvement was the cause of pulmonary infarction. Sarcoidosis is a significant risk factor for cardiovascular events. However, pulmonary infarction is an extremely rare complication of sarcoidosis. Our case suggests that sarcoidosis may cause vascular events in the lungs.

Adult-onset Still's disease-associated interstitial lung disease represents severe phenotype of the disease with higher rate of haemophagocytic syndrome and relapse.

OBJECTIVES: Adult-onset Still's disease (AOSD) is an inflammatory disorder characterised by sustained fevers, arthritis, and skin involvement. Interstitial lung disease (ILD) is a rare manifestation, and its clinical characteristics have yet to be determined. METHODS: We sought to examine the clinical characteristics of AOSD-associated ILD. We retrospectively investigated 78 patients diagnosed as AOSD. ILD was diagnosed based on chest high-resolution computed tomography (HRCT). Clinical characteristics were compared between patients with and without ILD. Relapse was defined as sustained fevers, re-emergence of arthritis, and skin involvement after remission. We further investigated the pathological features of ILD on available samples. RESULTS: Patients with ILD, found in 9 of 78 (11.5 %), had older age of onset (mean age 62.6) than those without ILD (mean age 38.8) (p<0.01). The 3-year survival rates were comparable between patients with ILD (92.5%) and those without ILD (88.9%) (p=0.23). Patients with ILD had a higher cumulative rate of haemophagocytic syndrome (HPS) and relapse than those without (p<0.0001 and p=0.009, respectively). Chest HRCT showed marked thickening of the interlobular septa, the bronchovascular bundles, or the visceral pleura in all cases. There was no honeycomb or volume loss. Pulmonary pathological findings revealed marked thickening of the visceral pleura and the interlobular septa. CONCLUSIONS: Patients with ILD might have higher risks for HPS and relapse. Careful observation and appropriate therapeutic intervention might be needed.

[A Case of Unclassified Sex Cord-Stromal Tumor Containing hCG-Positive Cells].

We present a case of unclassified sex cord-stromal testicular tumor with lung metastasis. A 48-year-old man consulted our hospital for left testicular enlargement that began 3 years ago. Computed tomography revealed a heterogeneously enhanced left testicular tumor 11 cm in diameter and a 5 mm metastatic lung tumor. The human chorionic gonadotropin (hCG) level was elevated (141.6 mU/ml), whereas the levels of α-fetoprotein (AFP) and LDH were normal. The external genitalia were normal and gynecomastia was not observed. Left high orchiectomy followed by 3 cycles of BEP chemotherapy (bleomycin, etoposide, and cisplatin) every 4 weeks was performed. The pathology of the excised specimen was unclassified sex cordstromal testicular tumor containing hCG-positive cells. On immunohistochemistry, the tumor cells were partly positive for AE1/AE3, hCG, and calretinin. Vimentin was diffusely positive, but OCT3/4, SALL4, GATA3, and CK7 were negative. After BEP treatment, the metastatic lung lesion disappeared. Unclassified sex cord-stromal testicular tumor is a rare disease and its treatment has not been established. Thus, further accumulation of cases is needed.

Grade 4 asbestosis does not extend directly from the respiratory bronchiole to the peripheral lung.

AIMS: To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung. METHODS AND RESULTS: We examined retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1 and ≥2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI) and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grades 0, 1 or ≥2 lesions, respectively, with mean respective numbers of ABs in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195 ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas and UIP patterns originated in subpleural, peripheral lobules. CONCLUSIONS: Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.

A case of combined small cell lung carcinoma with unique morphology: Investigation of tumorigenesis.

Small cell lung carcinoma (SCLC) usually grows in a pure form with no other associated histological components. However, combined small cell lung carcinoma (cSCLC), which is accompanied by other histological components (cSCLCs) may sometimes occur. Herein, we analyzed the tumorigenesis of cSCLC containing a demarcated area of pure SCLC. A 76-year-old man had a 25-mm mass in the perihilar portion of his right upper lung. Histologically, the cSCLC contained two relatively demarcated areas: one area composed of pure SCLC cells and another area of SCLC, squamous-like component (SLC), and spindle cell carcinoma (SpCC) cells. Loss of heterozygosity (LOH) was observed at allele 3p in all tumor components and at 22q in the pure SCLC component. Histological and immunohistochemical analysis and LOH study suggested that all components were likely to be monoclonal in origin and revealed that the pure SCLC component was not the precursor of the cSCLC. In the tumorigenesis of this case, the pure SCLC and the cSCLC may have originated from a common pluripotent tumor cell and then diverged, although we cannot state this conclusively. Further studies with more cases are necessary to test this theory.

Lung adenocarcinoma expressing receptor for advanced glycation end-products with primary systemic AL amyloidosis: a case report and literature review.

BACKGROUND: Receptor for advanced glycation end-products (RAGE), a receptor for amyloids, is constitutively expressed in lungs and generally observed to be downregulated in lung cancer tissues. However, increasing levels of RAGE or serum amyloids is associated with poor outcome in lung cancer patients. We report a rare case of primary systemic amyloid light-chain (AL) amyloidosis in biopsy-proven multiple organs with early-stage non-small cell lung cancer (NSCLC) that displayed strong staining for RAGE in the tumour tissue. Interestingly, compared with randomly selected lung cancer biopsy samples, including all representative histological subtypes of NSCLC and small-cell lung cancer, only the NSCLC in the present case showed strong expression for RAGE that can bind amyloids. CASE PRESENTATION: A 71-year-old woman was admitted to our hospital for comprehensive investigation of nephrotic syndrome. Computed tomography showed a small nodule in the right upper lung lobe with hilar mediastinal lymph node enlargement. Pathological examination of transbronchial biopsy samples of the nodule yielded a diagnosis of lung adenocarcinoma. Furthermore, the pathological detection of amyloid deposition in biopsy samples of a subcarinal lymph node, gastric and duodenal mucosa, cardiac muscle, and bone marrow led to a diagnosis of primary systemic AL amyloidosis with nephrotic syndrome and cardiomyopathy. In addition, RAGE was detected in lung tumour tissues surrounded by normal lung tissues with amyloid deposition. CONCLUSION: The RAGE positivity of the lung cancer cells in this case suggests an interaction between amyloid-containing tissues and RAGE-expressing cancer cells. Lung adenocarcinoma with RAGE expression may be a complication of underlying amyloidosis.

Gallbladder hemorrhage associated with segmental arterial mediolysis: a case report.

BACKGROUND: Gallbladder hemorrhage is a rare but fatal condition. The reported causes of gallbladder hemorrhage include iatrogenesis, atherosclerotic changes in the cystic arteries, acute cholecystitis or cholelithiasis, malignancy, trauma, hemophilia, pseudoaneurysm, and the use of oral anticoagulant medications. Recently, segmental arterial mediolysis (SAM) has been reported as a possible etiology of life-threatening abdominal, retroperitoneal, and intracranial hemorrhages. However, no previous reports have described the association between gallbladder hemorrhage and SAM. CASE PRESENTATION: A 59-year-old man was transferred to our hospital complaining of upper abdominal pain and vomiting. Contrast-enhanced computed tomography revealed high-density images of the gallbladder and common bile duct. However, there were no obvious findings of gallstones, cholecystitis, tumors, or aneurysms. He was diagnosed with gallbladder hemorrhage and bile duct obstruction. We performed a laparoscopic cholecystectomy after endoscopic biliary drainage. The gross appearance of the surgically resected specimen showed 12 small (3-12 mm), slightly elevated lesions on the gallbladder mucosa. Histologically, these slightly elevated lesions consisted of dilated muscular arteries of the gallbladder wall with fibrinoid degeneration of the media and focal loss of the internal and external elastic laminae. The histopathological diagnosis was confirmed as SAM. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a gallbladder hemorrhage associated with SAM. Our case report shows that SAM can cause gallbladder hemorrhage, suggesting that SAM should be considered in the differential diagnosis of gallbladder hemorrhage.

[A case with double primary cancers in both lung and nasal cavity].

Our patient, a 77-year-old male, underwent a medical examination for lower back pain. A careful investigation revealed two large tumors both in his lung and nose. The diagnosis was well-differentiated squamous cell carcinoma by biopsy in both sides. Radiation therapy(36 Gy)was performed on his nasal cavity, and nasal tumor volume was reduced considerably. Because the primary lesion could not be determined we used docetaxel chemotherapy which can be applied for both lung cancer and head and neck cancer. As a result, dissociation of the treatment's effect was seen, and we suspected the presence of overlapping cancer in both lung and nasal cavity. We could not use immunostaining to identify the primary lesion in squamous cell carcinoma as we did for adenocarcinoma. In this case we could infer the presence of overlapping cancer over the course of treatment with chemotherapy.

A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab-bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen.

A man in his eighties presented with a history of bilateral leg congestive phlebitis, and multiple hepatocellular carcinoma (HCC) treated with sorafenib. When the dose was increased to 400 mg, ulcers appeared under both knees, which worsened, and the drug was discontinued 2 months after administration. However, the ulcers to 30 mm in diameter, requiring debridement and antibiotics. The HCC showed a complete response (CR) based on modified-RECIST criteria; however, after several rounds of locoregional therapy for recurrence, multiple HCCs and metastatic lesions in the Morrison's fossa were detected. Therefore, atezolizumab 1200 mg-bevacizumab 900 mg was started. After the first course, the patient complained of pain below both knees, and when the second course was administered, leg ulcers re-appeared and rapidly worsened. The ulcers were circular and multiple and progressed to deep digging, leading to tendon exposure. Bevacizumab-induced congestive venous ulcer was diagnosed, requiring skin grafts to heal. HCC then showed a CR based on m-RECIST criteria. Initially, the cause of the ulcer was thought to be immune-related adverse effects due to atezolizumab, but experience with sorafenib led us to conclude that the cause was stagnant venous ulcers due to vascular endothelial growth factor receptor inhibitor, which inhibited angiogenesis.

ATS/JRS/ALAT Hypersensitivity Pneumonitis Guidelines for Diagnosis of humidifier lung and summer-type hypersensitivity pneumonitis.

BACKGROUND: The ATS/JRS/ALAT Guidelines for the Diagnosis of Hypersensitivity Pneumonitis (GL for HP) were published in 2020. Humidifier lung and summer-type HP are forms of HP, but it is unclear whether they can be diagnosed using GL for HP. This study examined the level of confidence where humidifier lung and summer-type HP can be diagnosed with GL for HP. METHODS: Data from 23 patients with humidifier lung and 20 patients with summer-type HP (mean age, 67.3 and 57.4 years, respectively) diagnosed between October 2012 and January 2022 were retrospectively reviewed. We evaluated high resolution computed tomography (HRCT) patterns, bronchoalveolar lavage fluid (BALF) findings, exposures, and histopathological findings to determine the level of confidence where a diagnosis of HP could be made using the GL for HP. RESULTS: HRCT pattern was classified as typical HP in 5 (22%) and compatible with HP in 18 (78%) patients with humidifier lung and considered as typical HP in 17 (85%) and compatible with HP in 3 (15%) patients with summer-type. The confidence level for diagnosis of HP was definite in 2 (8.7%), moderate in 14 (60.9%), and low in 7 (30.4%) patients with humidifier lung. It was definite in 12 (60%), high in 3 (15%), and moderate in 5 (25%) patients with summer-type HP. CONCLUSIONS: GL for HP showed utility in diagnosing humidifier lung in many patients with a moderate to low confidence. However, there was a definite to high confidence for patients with summer-type HP.

Occupational disparities in tumor grade and cytosolic HMGB1 expression in renal cell cancer.

OBJECTIVES: We sought to examine occupational disparities in tumor grade and cytosolic expression of high-mobility group box-1 (HMGB1) among renal cell cancer (RCC) patients. METHODS: This retrospective study included 318 RCC patients with complete information on occupation and pathology in Kanagawa Cancer Registry (KCR). Longest-held occupations were grouped into manual workers (e.g., manufacturing, construction) versus "others." Odds ratios (OR) and 95% confidence intervals (CI) for high-grade histology were estimated by logistic regression, adjusted for age and sex. We also examined a sub-sample of 74 low-grade RCC inpatients to estimate the OR for positive cytosolic HMGB1 expression in manual workers, adjusting for age, sex, and other available covariates. RESULTS: High-grade tumors were more prevalent in manual workers compared to other occupations: 23.0% (14/61) versus 10.9% (28/257, p = .01) with an adjusted OR of 2.28 (95% CI, 1.11-4.69). In the sub-sample of low-grade RCCs, positive cytosolic HMGB1 expression was more prevalent in manual workers compared to other occupations: 71.4% (10/14) versus 38.3% (23/60, p = .03) with a sex- and age-adjusted OR of 3.76 (95% CI, 1.03-13.7). CONCLUSIONS: Manual workers are associated with increased risks of high-grade renal cell tumors and cytosolic HMGB1 expression.

Cerebral Infarction Due to Occlusion of Main Trunk of Middle Cerebral Artery in Patient with Accessory Middle Cerebral Artery.

The existence of an accessory middle cerebral artery (AMCA) usually has no pathological significance. Three patients developed cerebral infarction due to thromboembolic occlusion of the main trunk of the middle cerebral artery (MCA). In these patients, AMCA originating from the anterior cerebral artery was intact, and ran to the lateral side along the main MCA. Emergency endovascular treatment to remove the thrombus in the main MCA was performed, and MCA was recanalized. In one patient, the main MCA re-occluded and cerebral infarction developed on the next day. The diameter of AMCA is commonly smaller than that of the main MCA. Therefore, volume of ischemic region depends on the collateral blood flow to the left MCA territory by AMCA. Once an anomalous MCA is detected in a patient with cerebral infarction involving the MCA territory, close examinations to assess the anatomy of both the main and anomalous MCA are mandatory.

Histopathological bronchial reconstruction of human bronchiolitis obliterans.

To clarify the morphological mechanisms of airway obliteration in bronchiolitis obliterans (BO) associated with various causes, we conducted a retrospective study of 9 patients with a histological diagnosis of BO. The morphological characteristics were analyzed by histopathological bronchial reconstruction. BO was classified into two major morphologic subtypes: constrictive BO (CoB) and cellular/destructive BO (CDB). CoB is characterized by concentric narrowing of the airway lumen due to submucosal fibrosis. In contrast, in CDB the narrowing of the airway lumen is due to intraluminal, mural, and peribronchiolar infiltration of inflammatory cells as well as proliferation of granulation tissue. The histopathological diagnosis was CoB in 6 patients and CDB in 3 patients. Macroscopic bronchial reconstruction in CoB demonstrated that the beginnings of bronchial obliterations were in the 4th to 7th branches, numbering from each segmental bronchus and the lesions were distributed intermittently. Histopathologically, the localization of obliteration was mainly from small bronchi to membranous bronchioli with intermittent airway luminal obliteration in CoB, whereas the primary lesions in CDB revealed more continuous obliteration of the bronchiolar lumen than observed in CoB. In conclusion, this bronchial reconstruction study demonstrated marked morphological differences in the mechanisms of airway obliteration between two major morphologic subtypes of BO.

Primary hepatic neuroendocrine carcinoma diagnosed by needle biopsy: a case report.

BACKGROUND: Primary hepatic neuroendocrine carcinomas (NECs) are extremely rare. The rate of recurrence after resection is extremely high, and the prognosis is poor. It is debatable whether chemotherapy or surgical resection is the optimal initial treatment for primary hepatic NECs. Therefore, selecting an appropriate therapeutic approach for patients with primary hepatic NECs remains clinically challenging. We present a case of primary hepatic NEC in a patient who developed recurrence after undergoing surgical resection. CASE PRESENTATION: A 78-year-old man with bone metastases of prostate cancer was referred to our department because of a solitary 66-mm tumor in the left lateral segment of the liver, which was detected on annual follow-up by computed tomography after prostate resection. A biopsy and preoperative diagnostic workup identified the lesion as a primary hepatic neuroendocrine carcinoma; therefore, left lateral segmentectomy was performed. Immunohistochemically, the tumor was positive for chromogranin A, synaptophysin, and CD 56, and the Ki-67 index was 40%. This neuroendocrine carcinoma was classified as a large cell type. Adjuvant chemotherapy with carboplatin + etoposide was initially administered a month after surgery. However, lymph node recurrence occurred 4 months after surgery, and the patient died of systemic metastases 15 months after surgical resection. CONCLUSIONS: Due to the lack of availability of abundant quantities of relevant, high-quality data, there is no standard therapy for primary hepatic NECs. Selecting the most appropriate treatment for patients depending on several factors, such as the stage and differentiation of a tumor and a patient's performance status and clinical course, is consequently preferred. More cases need to be studied to establish the best treatment strategy for primary hepatic NEC.

Collision tumor of primary malignant lymphoma and adenocarcinoma in the colon: report of a case.

This report presents the case of a 62-year-old man with a collision tumor of primary malignant lymphoma and adenocarcinoma in the cecum. All regional mesenteric lymph nodes that were removed surgically were found to be occupied by lymphoma cells and no lymph nodes contained any cancer cells, although the primary carcinomas did exhibit lymphatic invasion. Malignant lymphoma was also seen in the duodenum. Systemic chemotherapy was administered for the malignant lymphoma, and a complete response was thus obtained. However, just after chemotherapy multiple liver metastases of adenocarcinoma emerged, and chemotherapy against adenocarcinoma was therefore continued. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectum is rare. Furthermore, collisions of these different entities are also extremely unusual; so far only five such case reports have been published. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

Solitary pancreatic metastasis of gastric cancer with synchronous pancreatic ductal carcinoma: A case report.

BACKGROUND: There have been a few reports on solitary pancreatic metastases of gastric cancer. We present a case of solitary pancreatic metastasis of gastric cancer with synchronous primary pancreatic ductal carcinoma. PRESENTATION OF CASE: An 86-year-old man who had undergone total gastrectomy two and half years prior presented with a poorly enhanced tumor in the pancreatic body. We diagnosed pancreatic ductal carcinoma and performed distal pancreatosplenectomy. Histopathologically, the tumor comprised poorly differentiated adenocarcinoma cells mixed with moderately differentiated tubular adenocarcinoma cells that were compatible with metastasis of gastric cancer. There was also invasive ductal carcinoma of the pancreas. The postoperative course was uneventful. Six months after surgery, computed tomography revealed peritoneal dissemination, and he died of recurrence 10 months after surgery. CONCLUSION: Pancreatic metastasis of gastric cancer with synchronous primary pancreatic cancer can occur and should be considered in the differential diagnosis.

Morphological Change of Cerebral Aneurysm with Possible Pseudoaneurysm at A2/3 of the Anterior Cerebral Artery on Three-dimensional Computed Tomographic Angiography.

Intracranial pseudoaneurysm formation due to a ruptured nontraumatic aneurysm is rare. We describe a case of ruptured aneurysm, which showed morphological change on radiological examinations. An 83-year-old woman developed subarachnoid hemorrhage (SAH) with ventricular rupture and intracerebral hematoma in the corpus callosum. Contrast-enhanced computed tomography (CE-CT) demonstrated an aneurysm at the right A2/3 junction of the anterior cerebral artery. CE-CT repeated 17 h after the initial one showed shortening of the lesion on both three-dimensional and raw images. The aneurysm was surgically clipped. In cases of SAH with a hematoma or thick SAH, there is a possibility that a pseudoaneurysm will form at the tip of the true aneurysm in an adjacent thrombus or existence of intraluminal thrombus. The morphology may change during the period between initial radiological evaluation and the operation in these cases. We should be aware that the intraoperative findings or subsequent radiological findings might be different from those observed on preoperative radiological examinations.