A case of adrenal metastasis of hepatocellular carcinoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

An 82-year-old man had been treated for lung adenocarcinoma and hepatocellular carcinoma (HCC). Contrast-enhanced computed tomography examination showed swelling of the left adrenal gland, suggesting metastasis of lung adenocarcinoma, HCC, or primary adrenal tumor. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed for the pathological diagnosis, and adrenal metastasis of HCC was diagnosed. No notable complications due to EUS-FNA were found. There have been reports of adrenal metastasis due to various cancers, but there are few reports that can confirm the diagnosis of adrenal metastasis of HCC using EUS-FNA. Adrenal metastasis of HCC is not a rare condition, but it may be difficult to diagnose in the case of multiple cancer complications. We experienced a case in which EUS-FNA was useful for the diagnosis of adrenal metastasis of HCC.

Case report: Pathological complete response of pregnancy associated pulmonary enteric adenocarcinoma to chemoradiotherapy.

Pulmonary enteric adenocarcinoma (PEAC) is a rare lung adenocarcinoma with morphological features similar to those of primary and metastatic colorectal adenocarcinoma. To date, only a few studies have reported the therapeutic effects of chemoradiotherapy on PEAC. This report describes the case of a 28-year-old woman with pregnancy-related PEAC who presented with left shoulder pain. A superior sulcus tumor was identified in the left thoracic cavity, and the biopsy indicated more than 50% intestinal differentiation components. Moreover, immunohistochemical staining revealed positive CDX2 and CK7 expression. Positron emission tomography-computed tomography, upper endoscopy, colonoscopy, and small intestinal capsule endoscopy revealed no gastrointestinal malignancies. The patient was diagnosed with locally advanced PEAC (clinical stage T4N0M0; stage IIIA). Therefore, the patient was treated with preoperative chemoradiotherapy and underwent gross total resection during surgery. Pathological evaluation of the specimen revealed no residual tumor, indicating that the chemoradiotherapy for PEAC was highly effective. One subsequent brain metastasis was also resected, and the patient has not experienced recurrence in 28 months since this resection and continues to be monitored regularly. This is the first pathologically confirmed report of the use of chemoradiotherapy (carboplatin [CBDCA] and paclitaxel [PTX]) for PEAC and its clinical efficacy. Unlike previous reports, the efficacy of this treatment is attributed to the use of PTX in preoperative chemotherapy and the p21- status of the patient, which may have increased sensitivity to chemoradiation therapy. Therefore, chemoradiotherapy (CBDCA + PTX) may be a viable treatment option for advanced intestinal lung adenocarcinoma.

Peritumoral Fat Content Identified Using Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-squares Estimation (IDEAL) Correlates with Breast Cancer Prognosis.

PURPOSE: Adipocytes around aggressive breast cancer (BC) are less lipid different from naive adipocytes (cancer-associated adipocytes, CAAs), and peritumoral edema caused by the release of cytokines from CAAs can conduce to decrease the peritumoral fat proportion. The purpose of this study was to correlate peritumoral fat content identified by using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with lymph node metastasis (LNM) and recurrence-free survival (RFS) in BC patients and to compare with T2-weighted (T2WI) and diffusion-weighted images (DWI) analyses. METHODS: This retrospective study consisted of 85 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI, including IDEAL before surgery. The scan time of fat fraction (FF) map imaging using IDEAL was 33s. Four regions of interest (ROIs), which are 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (TFF), average FF values on the healthy side (HFF), and peritumoral fat ratio (PTFR, which is defined as TFF/HFF) were calculated. Tumor apparent diffusion coefficient (ADC) values were measured on ADC map obtained by DWI. Peritumoral edema was classified into three grades based on the degree of signal intensity around the tumor on T2WI (T2 edema). RESULTS: The results of stepwise logistic regression analysis for four variables (TFF, PTFR, T2 edema, and ADC value) indicated that TFF and T2 edema were significant factors of LNM (p < 0.01). RFS was significantly associated with TFF (p = 0.016), and 47 of 49 (95.9%) patients with TFF more than 85.5% were alive without recurrence. CONCLUSION: Peritumoral fat content identified by using IDEAL is associated with LNM and RFS and may therefore be a useful prognostic biomarker for BC.

Difficulty differentiating primary mediastinal classical Hodgkin lymphoma from inflammatory myofibroblastic tumor: A case report.

A 20-year-old Japanese man visited our hospital because an enlarged mediastinal shadow had been detected on chest x-ray. Chest computed tomography revealed a large mediastinal mass with multiple lymph node enlargement, pericardial effusion, and bilateral pleural effusion. He was diagnosed with inflammatory myofibroblastic tumor (IMT) based on a thoracoscopic tumor biopsy. Initial corticosteroid and celecoxib treatment was only partially effective; therefore, additional tumor rebiopsy and left axillary lymph node biopsy were performed. Based on the findings, the patient was rediagnosed with classical Hodgkin lymphoma (CHL). To date, there has only been one report of a case initially diagnosed as IMT and rediagnosed as CHL, as in our case, and only three reports of malignant lymphoma mimicking IMT. When IMT is suspected based on pathological findings and subsequently with treatment failure, possible CHL and performing rebiopsy should be considered.

Prognostic factors of resected pathological stage I lung adenocarcinoma: evaluating subtypes and PD-L1/CD155 expression.

We aimed to compare the prognostic impacts of adenocarcinoma subtypes, programmed death-ligand I (PD-L1), and CD155 expression on patients with resected pathological stage (p-stage) I lung adenocarcinoma. In total, 353 patients with completely resected p-stage I lung adenocarcinomas were retrospectively reviewed. The expression levels of PD-L1 and CD155 in tumour cells from each adenocarcinoma subtype were evaluated using several clinicopathological and histological features, such as the presence of a micropapillary pattern. A total of 52 patients (14.7%) had PD-L1-positive tumours, whereas 128 patients (36.3%) had CD155-positive tumours, with a tumour proportion score of 5% for both PD-L1 and CD155 expression. Compared with patients with other adenocarcinoma subtypes, those with solid-predominant adenocarcinomas were significantly more positive for PD-L1 and CD155. Multivariate analysis showed that PD-L1 expression status was significantly associated with progression-free survival and overall survival, whereas CD155 expression and the presence of a micropapillary pattern were not significantly associated with either parameter. Patients with PD-L1-positive tumours had poorer prognoses than those with CD155-positive tumours. Moreover, PD-L1 and CD155 were significantly expressed in solid-predominant adenocarcinomas. The results of this study suggest that immune checkpoint inhibitors can be used as adjuvants in the treatment of patients with p-stage I adenocarcinoma.

Small cell carcinoma of the kidney treated with immune checkpoint inhibitor/tyrosine kinase inhibitor.

Introduction: Small cell carcinoma (SCC) of the kidney is extremely rare. Although the majority of patients with advanced renal small cell carcinoma were treated with a combination of cisplatin and etoposide, the efficacy was limited. We report the first case with renal small cell carcinoma who received nivolumab and cabozantinib. Case presentation: A 57-year-old woman was referred to our hospital with a massive left kidney mass and several bone, lymph nodes, liver, and lung metastases. A left renal mass biopsy made the diagnosis of small cell carcinoma. Nivolumab and cabozantinib were used in combination therapy. The tumors were stable during the treatment for 4 weeks. However, the treatment was halted due to a serious adverse event, immune-related hemophagocytic lymphohistiocytosis. Although immune-related hemophagocytic lymphohistiocytosis was resolved with corticosteroids, the patient died 3 months after the initiation of nivolumab and cabozantinib. Conclusion: We reported the first case of renal small cell carcinoma treated with nivolumab and cabozantinib.

Association of troponin I and macrophages in cardiac tamponade with Stanford type A aortic dissection.

Background: Acute aortic dissection has a high mortality rate, especially for Stanford type A with a dissected ascending aorta. Cardiac tamponade is one of the most common complications of acute type A aortic dissection (ATAAD) and can cause death. However, the pathogenesis is often unclear. We aimed to examine laboratory findings at the onset of disease and macrophage involvement. Methods: Hematological and biochemical parameters, and D-dimer, brain natriuretic peptide (BNP), and high-sensitivity troponin I (hs-cTnI) levels in 70 patients with ATAAD at our hospital were investigated. Additionally, the myocardium and aorta after autopsy of an ATAAD case with cardiac tamponade were pathologically examined. Results: Forty-four ATAAD cases were complicated by cardiac tamponade. The mean age of patients with cardiac tamponade and proportion of patients over 70 years of age were both significantly higher than for those without cardiac tamponade. Evaluable D-dimer values were higher than 0.5 µg/mL in all patients. Significantly elevated laboratory parameters in patients with cardiac tamponade included: lactate dehydrogenase, aspartate aminotransferase, C-reactive protein, lactate, BNP, and hs-cTnI. However, multivariate analysis showed only hs-cTnI was significantly associated with cardiac tamponade. Histological examination revealed numerous M2-like macrophages infiltrating the myocardium and dissecting aorta, expressing CC chemokine ligand (CCL)2 together with vascular endothelial growth factor-C and matrix metalloproteinase-9. The peripheral monocyte-to-neutrophil ratio (MNR) was also significantly higher in cardiac tamponade. Conclusions: In ATAAD patients with cardiac tamponade, hs-cTnI was significantly elevated and CCL2 expression was observed, which may be involved in the expression of M2-like macrophages via an increased MNR.

IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report.

We reported a case of molecularly defined isocitrate dehydrogenase (IDH)-mutant astrocytoma that recurred twice with aggressive behavior and increased anaplastic morphology. Primary and recurrent tumors were analyzed using custom-made DNA-based cancer gene and RNA-based fusion panels for next-generation sequencing (NGS). NGS analyses revealed that recurrent astrocytoma, in addition to IDH1 and tumor protein 53 mutations detected in the primary lesion, harbored cyclin-dependent kinase inhibitor (CDKN) 2 A/B homozygous deletion and neurotrophic tropomyosin receptor kinase 2 (NTRK2) fusion genes that consisted of golgin A1- and cyclin-dependent kinase 5 regulatory subunit associated protein 2-NTRK2 fusions. Anaplasia and necrosis were observed in the recurrent tumors, but not in the primary lesion. Therefore, the integrative diagnosis was primary IDH-mutant astrocytoma grade 2 and recurrent IDH-mutant astrocytoma grade 4 with NTRK2 fusions. This is a worthwhile report describing a case of IDH-mutant astrocytoma that showed genomic evolution during tumor recurrence. Our report suggests that NTRK fusion and CDKN2A/B homozygous deletion promote high-grade transformation and indicate an unfavorable prognosis of IDH-mutant astrocytoma.

Relationship of histamine expression with chemokine balance in the tumor microenvironment of squamous cell carcinoma of the tongue.

BACKGROUND: Tumor-associated macrophages in the tumor microenvironment (TME), as a factor affecting lymphocytes, have received much attention. Both lymphocytes and macrophages can switch the expression of histamine receptors. In this study, we investigated the role of histamine in the TME of tongue squamous cell carcinoma (SCC). METHODS: Sixty-seven patients with stage I tongue SCC were studied. Histamine was evaluated by the expression of L-histidine decarboxylase (HDC). Macrophages, T lymphocytes, and lymph vessel density, as well as the Ki-67 labeling index (LI) and depth of invasion (DOI), were compared with HDC expression. RESULTS: HDC expression was significantly affected by the TME. The DOI, worst pattern of invasion, and Ki-67 LI were associated with histamine expression. C-C motif chemokine ligand (CCL) 2 and CCL22 were co-expressed with histamine H1 and H2 receptors. Histamine expression was most affected by the DOI. CONCLUSIONS: Tongue SCC expressing histamine affected the TME via histamine receptors and chemokines.

Salvage surgery following immuno-chemo-radiotherapy for advanced non-small cell lung cancer.

BACKGROUND: Salvage surgery following definitive radiotherapy or systemic treatment has become a feasible treatment option in selected patients with advanced initially unresectable non-small cell lung cancer. Recent clinical trials of neoadjuvant treatment have showed that surgery following immuno-chemotherapy is safely performed. Here, we present the first case of salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced lung large cell carcinoma. CASE PRESENTATION: A 44-year male was admitted to our hospital for salvage surgery. Ten months prior to this administration, he had been diagnosed with unresectable large cell carcinoma with malignant pericardial effusion (clinical stage IVA/T3N2M1A; no driver-gene alteration) originating from the right upper lobe (RUL). Due to rapid intrabronchial tumor growth causing severe dyspnea, emergency bronchial stenting in the right main bronchus using an expandable metallic stent had been performed. Thereafter, he had received immuno-chemotherapy with concurrent definitive radiotherapy. Despite dramatic radiographic response, he had suffered from persistent and refractory Pseudomonas aeruginosa lung infection associated with bronchial stent placement. As pericardial effusion had disappeared and no distant metastasis had developed, he was diagnosed with a potentially curable disease and was referred to our hospital. An extended sleeve resection was successfully performed, and pathological sections revealed that pathologic complete response was achieved with immuno-chemo-radiotherapy. The patient received no subsequent treatment, and is alive without tumor recurrence at 8 months after surgery. CONCLUSIONS: Salvage surgery following immuno-chemotherapy with concurrent definitive radiotherapy for advanced non-small cell lung cancer may be feasible in selected patients, and may be considered as a treatment option to control local disease.

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers.

BACKGROUND: The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated. METHODS: Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs. RESULTS: Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01). CONCLUSION: Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

Hepatocyte Growth Factor and Primary Systemic Amyloidosis.

A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.

Sinusitis of actinomycosis infection†:†a case report.

Actinomycosis is an infection caused by anaerobic bacteria, primarily from the genus Actinomyces, which normally colonize the several regions including the mouth. Disruption of mucosa may lead to infection of virtually any site, but reports of involvement of the sinuses are rare. We report a case of an actinomycosis infection in the unilateral maxillary sinus. A 47-year-old female visited our hospital with a complaint of mild pain of left buccal region. Computed tomography (CT) revealed that the left maxillary and anterior ethmoidal sinus cavities were opacified along with a calcified fragment located close to the natural ostium. Thus, we provisionally diagnosed as a fungal sinusitis. She underwent trans-nasal endoscopic sinus surgery. The sinuses were opened and the caseous material was removed. The histopathological examination suggested an actinomycosis, but not fungal, infection. The patient's postoperative course was uneventful. No evidence of recurrence has been seen over the 30 months of the postoperative follow-up period. In case of the aggressive actinomycotic sinusitis, extension into the adjacent organs could be occurred. We should be aware that sinusitis of actinomycosis infection could progress in patients with risk factors such as diabetes and immunodeficiency. J. Med. Invest. 68 : 202-204, February, 2021.

CD169 Expression on Lymph Node Macrophages Predicts in Patients With Gastric Cancer.

The induction of an anti-cancer immune responses is potentially associated with the efficacy of anti-cancer therapy. Recent studies have indicated that sinus macrophages in regional lymph nodes are involved in anti-cancer immune responses in the cancer microenvironment. In the present study, we investigated the correlation between lymphocyte infiltration in cancer tissues and macrophage activation in regional lymph nodes. We retrospectively identified 294 patients with gastric cancer who underwent surgery from 2008 to 2012. Using immunohistochemistry, we evaluated CD169-expression on CD68-positive macrophages, and the density of CD8-postive lymphocytes in tumor microenvironment. We statistically examined the correlation between CD169 and CD8 expression, and performed Cox regression analysis of potential prognostic factors, including CD169 and CD8 expression, for cancer-specific survival (CSS) in patients with total and advanced gastric cancer. CD169 overexpression in lymph node sinus macrophages (LySMs) was positively correlated to the density of CD8-positive lymphocytes in primary cancer tissues (R = 0.367, p < 0.001). A high density of CD8-positive T lymphocytes in the primary site and a high level of CD169 expression in LySMs were independently associated with greater CSS in patients with total and advanced gastric cancer (p < 0.05 for all). The expression on CD169 in LySMs is a predictor of a favorable clinical course in patients with gastric cancer, and might be useful for evaluating anti-cancer immune responses.

An elderly-onset neuroblastoma concomitant with minimal change nephrotic syndrome: the first autopsy case report.

BACKGROUND: Neuroblastoma is a well-known embryonal cancer; however, adult-onset neuroblastomas are rare. The systemic symptoms are related to catecholamine excretion or intraabdominal mass effects. Only two cases of neuroblastoma with nephrotic syndrome have previously been reported. We herein present the first autopsy case of neuroblastoma in an older individual associated with minimal change nephrotic syndrome. CASE PRESENTATION: A 63-year-old man was admitted to our hospital for investigation of general fatigue. His renal function was normal and his urine was negative for protein. A computed tomography scan showed a renal tumor and intraabdominal lymph node swelling. Approximately 4 months after admission, he suddenly developed acute renal failure and severe proteinuria, and hemodialysis was instituted. A computed tomography scan revealed an increase in the size of the renal tumor and lymph nodes. He died 1 month later and an autopsy was performed. The tumor exhibited diffuse proliferation of tumor cells with scant cytoplasm, namely small blue cell tumor with rosette formation. As a result of immunohistochemical study, a neuroblastoma was diagnosed. Despite the patient's severe renal failure, most glomeruli showed no remarkable changes. The tubular epithelium exhibited detachment and vacuolation. Electron microscopic study of the glomeruli showed diffuse effacement of the foot processes. These features indicate a diagnosis of minimal change nephrotic syndrome with acute tubular injury. CONCLUSIONS: Minimal change nephrotic syndrome is the most common renal manifestation associated with lymphoproliferative malignancies. We here present an extremely rare case of adult-onset neuroblastoma with minimal change nephrotic syndrome.

Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.

Hemochromatosis is a clinical syndrome characterized by iron overload in various organs. We present here a case of type 4 hereditary hemochromatosis due to heterozygous mutation in SLC40A1 gene (p.D157A). SLC40A1 encodes ferroportin, a macromolecule only known as iron exporter from mammalian cells. He first presented symptoms correlated with hypopituitarism. Furthermore, marked hyperferritinemia and high transferrin saturation were revealed in combination with the findings of iron overload in the liver, spleen and pituitary gland by computed tomography and magnetic resonance imaging. Liver biopsy revealed iron deposition in both hepatocytes and Kupffer cells. SLC40A1 mutations are considered to cause wide heterogeneity by various ferroportin mutations. Thus, clinicopathological examinations seem to be very important for diagnosing phenotype of type 4 hemochromatosis in addition to the gene analysis. We diagnosed him as type 4B hereditary hemochromatosis (ferroportin-associated hemochromatosis) by the findings of high transferrin saturation and iron deposition in hepatocytes, and then started iron chelating treatment. We should suspect the possibility of hereditary hemochromatosis even in Japanese with severe iron overload. Although the same mutation in SLC40A1 gene (p.D157A) had been reported to cause "loss of function" phenotype, we considered that the mutation of our case caused "gain of function" phenotype.

Peritumoral Fat Content Correlates with Histological Prognostic Factors in Breast Carcinoma: A Study Using Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL).

PURPOSE: To correlate peritumoral fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with histologic prognostic factors in breast carcinoma. MATERIALS AND METHODS: This study consisted of 100 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI including IDEAL before surgery. The scan time of IDEAL fat fraction (FF) map imaging was 33 s. Four regions of interests (ROIs), which are a distance of 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (FFt), average FF values in the healthy side (FFh), and peritumoral fat ratio (pTFR: defined as FFt/FFh) were calculated. Histologically, the presence of lymph node metastasis and the MIB-1 index were evaluated. RESULTS: FFt and pTFR for breast carcinoma with lymph node metastasis (79.27 ± 10.36 and 0.897 ± 0.078) were significantly lower than those without (86.23 ± 4.53 and 0.945 ± 0.032) (P < 0.001 and P = 0.005). Spearman rank correlation suggested that the FFt correlated with the MIB-1 index (r = -340, P = 0.001). CONCLUSION: Quantification of peritumoral fat using IDEAL-iron quantification is associated with the histologic prognostic factors, and may be a practical tool for therapeutic strategy of breast carcinoma.

Significant delayed aortic dilatation after tetralogy of Fallot repair: a case report.

BACKGROUND: Aortic dilatation may occur in some patients even after complete repair of tetralogy of Fallot (TOF). The progression rate of the aortic diameter is so slow, and the incidence of aortic dissection is so low that it is suspected that frequent imaging of the aorta may not be necessary. CASE PRESENTATION: We describe an asymptomatic 41-year-old man with hypertension in whom aortic dilatation was accidentally discovered 39 years after TOF repair. He underwent ambulatory follow-up without any difficulty for 21 years after the repair. Contrast-enhanced computed tomography revealed significant aortic dilatation (maximum diameter of 88 mm at the sinus of Valsalva), and echocardiography revealed severe aortic regurgitation, which seemed to progress during the last 18 years without any evaluation or follow-up. The Bentall procedure was successfully performed using a valved graft, under deep hypothermic circulatory arrest with antegrade cerebral perfusion, and his postoperative course was uneventful. Histopathological examination of ascending aorta specimens revealed severe cystic medial degeneration. CONCLUSIONS: Keeping in mind that a patient with rapid progression of the aortic dilatation after TOF repair exist, periodic follow-up for evaluation of the aorta is essential in patients with TOF.