Search

A patient with GATA2 deficiency developed corticosteroid-responsive sterile granulomatous lung disease despite monocytopenia. The presence of B-lymphopenia, autoimmunity, an elevated level of serum B-cell–activating factor, and pulmonary plasma cell infiltration, which together suggested an underlying mechanism similar to that of combined variable immunodeficiency lung disease.

Abstract Despite the dedicated research of artificial intelligence (AI) for pathological images, the construction of AI applicable to histopathological tissue subtypes, is limited by insufficient dataset collection owing to disease infrequency. Here, we present a solution involving the addition of supplemental tissue array (TA) images that are adjusted to the tonality of the main data using a cycle-consistent generative adversarial network (CycleGAN) to the training data for rare tissue types. F1 scores of rare tissue types that constitute

Abstract Background Follicular cholangitis (FC) is a benign bile duct disease that was first reported 2003. Pathologically, it is characterized by lymphoplasmacytic infiltration with multiple lymphoid follicle formations under the mucosal layer of the biliary tract. However, as this disease is extremely rare, little is known about its etiology and pathogenesis. Case presentation A 77-year-old woman was diagnosed with middle bile duct stenosis and potential increases in alkaline phosphatase (ALP) and γ-glutamyl transpeptidase levels (γ-GTP). Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and IgG4 levels were all within the normal limits. Contrast-enhanced computed tomography (CE-CT) and magnetic resonance imaging (MRI) revealed bile duct dilation from intrahepatic to upper common bile duct and an irregular mass lesion in distal bile duct. Additionally, multiple overlapping leaf-like folds were detected. 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT) did not demonstrate fluorodeoxyglucose uptake. Subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection was performed because common bile duct cancer could not be ruled out. The resected specimen showed diffuse homogeneous middle bile duct wall thickening. Microscopically, the lesion exhibited thick fibrosis with several invaded lymphoplasmacytic cells, and lymphoid follicle formations were detected under the mucosal layer. Immunohistochemical staining (IHC) revealed positive for CD3, CD4, CD20 and CD79a, and these findings led to a final diagnosis of FC. The patient has not experienced recurrence to date (42 months postoperatively). Conclusions Currently, accurate preoperative diagnosis of FC is difficult. More cases must be accumulated to generate additional knowledge on its precise diagnosis and proper treatment.

Introduction Ewing sarcoma family tumor is a malignant tumor that is primarily of bone origin; it rarely occurs in the kidney. Case presentation A 22‐year‐old woman presented with hematuria. Computed tomography revealed a 6 × 6‐cm mass in the lower pole of the right kidney with invasion into the right renal vein. A right laparoscopic radical nephrectomy was performed. The tumor was completely encapsulated. Based on the small‐round‐cell histology, diffusely CD99‐positive tumor cells, and EWS (ex7)–FLi1 (ex6) fusion gene break point transcript, we diagnosed Ewing sarcoma/primitive neuroectodermal tumor of the kidney. After surgery, eight cycles of adjuvant chemotherapy including vincristine, doxorubicin (Adriamycin®), cyclophosphamide, ifosfamide, and etoposide were given. No evidence of recurrence has been observed 13 months from diagnosis. Conclusion This was a rare Ewing sarcoma family tumor in the kidney of a young female with no remarkable family medical history.

Arachidonic acid 5-lipoxygenase (5-LOX), an enzyme that synthesizes leukotrienes (LTs), is involved in cancer development including proliferation, invasion, metastasis and drug resistance. However, the functional role of 5-LOX in hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we analyzed the contribution of 5-LOX in HCC progression and investigated the potential of targeted therapy. Analysis of 86 resected HCC specimens and the clinical data of 362 cases of liver cancer from The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, showed that 5-LOX expression was associated with postoperative survival. The cancer proliferative and stem cell potential were correlated with the levels of 5-LOX in CD163(+) tumor-associated macrophages (TAMs). In an HCC mouse model, CD163(+) TAMs expressed 5-LOX and produced LTB4 and LTC/D/E4; the 5-LOX inhibitor, zileuton, suppressed HCC progression. LTB4 and LTC/D/E4 promoted cancer proliferation and stem cell capacity via phosphorylation of extracellular signal-regulated kinase 1/2 and stem cell-associated genes. Taken together, we identified a novel mechanism of HCC progression in which CD163(+) TAMs express 5-LOX and produce LTB4 and LTC/D/E4, thereby enhancing the proliferative and stem cell potential of HCC cells. Furthermore, inhibition of 5-LOX activity regulates HCC progression, suggesting it has potential as a new therapeutic target.

Abstract Background Heterotopic ossification (HO) is the formation of osseous tissue outside the skeleton. HO in malignant tumors of the digestive tract is extremely rare, as is ossification in metastatic lesions from HO-negative digestive tract tumors. Regarding the pathogenesis of HO, two theories have been proposed. The first is that the osteoblastic metaplasia of tumor cells (driven by the epithelial-mesenchymal transition, EMT) results in HO, and the second is that factors secreted by cancer cells lead to the metaplasia of stromal pluripotent cells into osteoblasts. However, the osteogenic mechanisms remain unclear. Case presentation An 83-year-old Japanese woman underwent low anterior rectal resection for rectal cancer before presentation at our institution, in June 2018. The final diagnosis was stage IIB rectal adenocarcinoma (T4aN0M0). Histological examination did not reveal HO in the primary tumor. Thirteen months after the operation, a solitary metastatic lesion in the brain 20 mm in size and a solitary metastatic lesion in a right axillary lymph node 20 mm in size were diagnosed. The patient was treated with gamma-knife therapy for the brain metastasis. One month later, she was referred to our institution. She underwent lymph node resection. Histological examination revealed that most portions of the affected lymph node were occupied by metastatic tumor cells and that central necrosis and four small ossified lesions without an osteoblast-like cell rim were present in the peripheral region. Immunohistochemical analysis showed tumor cells positive for BMP-2, osteonectin, osteocalcin, AE1/AE3, TGF-β1, Gli2, Smad2/3, and CDX2 and negative for nestin, CD56, and CK7. Conclusion This is the first English case report of HO in a metachronous metastatic lymph node after the curative resection of HO-negative rectal cancer. Unlike HO lesions in past reports, the HO lesion did not show peripheral osteoblast-like cells, and the immunohistochemical findings indicated that the present case resulted from the EMT.

Abstract Background Pancreatic hamartomas are rare entities and difficult to diagnose before resection. We report a case of resected pancreatic hamartoma and literature review of typical characteristics of the lesion. Case presentation A 78-year-old man presented with a mass in his pancreas, which was incidentally identified when he experienced pneumonia. No remarkable symptoms were observed, and laboratory tests showed no abnormalities, except a slight carcinoembryonic antigen elevation. Enhanced computed tomography and magnetic resonance imaging showed a well-demarcated solid mass with heterogeneous contrast that was 2 cm in size. A gradual enhancement pattern was also observed. The biopsy revealed no specific findings; therefore, surgical resection was necessitated to confirm the diagnosis. Histopathologically, ducts, acinar cells, and adipose cells without atypia were observed among abundant fibrous stroma, but islets of Langerhans and peripheral nerves were absent. An immunohistochemical examination demonstrated CD34 and c-kit positive staining in the stromal cells, S-100 positivity in the adipose cells, and a lack of elastic fibers in the duct walls. The lesion was diagnosed as a pancreatic hamartoma. Conclusion Asymptomatic pancreatic hamartomas can avoid resection. A careful consideration of imaging and appropriate immunohistochemistry of biopsy specimen may facilitate accurate diagnosis before resection. Therefore, sufficient recognition of the characteristics of pancreatic hamartomas is desirable.

Abstract Background It has been recently accepted that IgG4-related thyroiditis is comparable to the Hashimoto and Riedel thyroiditis and Graves disease which are rich in IgG4-secreting plasma cells. Many physicians believe that in IgG4-related thyroiditis, the thyroid is entirely enlarged and diffusely affected, which is similar to conventional thyroiditis, but rarely ever accompanied by pseudoneoplastic mass formation as in IgG4-related disease in the other organs. This report introduces another pattern of IgG4-related thyroiditis as mass-forming thyroiditis and presents the occurrence of IgG4-related regional lymphadenopathy as an unusual accompanying symptom. Case presentation A 66-year-old woman presented with an approximately 2.5-cm mass in the right thyroidal lobe and regional lymph node swelling, which were preoperatively misinterpreted as thyroidal carcinoma. After lobectomy, histological examination was performed, revealing that the mass showed dense stromal fibrosis, lymphoplasmacytic infiltration, and effacement of thyroid follicles, while the background thyroidal tissue seemed to mimic lymphocytic thyroiditis without fibrosis. Immunohistochemistry revealed predominance of IgG4-secreting plasma cells among infiltrating lymphocytes independent of mass lesion or background tissue. In addition, the regional Delphian and paratracheal lymph nodes were swollen, histologically showing numerous IgG4-secreting plasma cell infiltrations in the interfollicular zone. Conclusions IgG4-related mass-forming thyroiditis, which may be an extremely rare but recognizable pattern of IgG4-related thyroiditis, may be distinguishable from Hashimoto and Riedel thyroiditis, Graves disease, and thyroidal carcinoma. In addition, the regional IgG4-related lymphadenopathy, also possibly misdiagnosed as metastatic thyroidal carcinoma, may be a newly recognized manifestation of IgG4-related thyroiditis.

Background and study aims Duplication cysts of the ileum are rare and present with non-specific clinical manifestations such as abdominal pain, vomiting, melena, and intussusception. Therefore, preoperative diagnosis is difficult. Here, we report a case of duplication cyst of the small intestine that was diagnosed preoperatively using double-balloon enteroscopy. A 19-year-old man presented with severe iron deficiency anemia, abdominal pain, and exertional dyspnea. Gastroscopy and colonoscopy revealed no remarkable findings. Abdominal computed tomography revealed a cystic structure in the ileum. Therefore, we performed double-balloon enteroscopy via the anal route. The intestinal tract was bifurcated, with one segment ending in a blind sac containing normal villi and an ulceration. Tc-99 m pertechnetate scintigraphy showed no accumulation in the lesion. Accordingly, we diagnosed a duplication cyst and suspected that this was the cause of severe anemia. Following small bowel resection with cyst excision and anastomosis, the anemia and presenting symptoms resolved. This report highlights the usefulness of double-balloon enteroscopy of the small intestine for preoperative diagnosis of the obscure gastrointestinal bleeding, including duplication cysts.

Renal metastasis at diagnosis with neuroblastoma is rare. We present a 14-month-old boy who was diagnosed with high-risk neuroblastoma with multiple metastases, including bilateral kidneys. He received five cycles of induction chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. All of the lesions shrank, and magnetic resonance imaging indicated that some of the metastases had disappeared. However, there were residual masses in the bilateral kidneys, and histological examination revealed the presence of tumor cells. Therefore, the patient underwent unrelated cord blood stem cell transplantation, which involved killer-ligand incompatibility in the graft-versus-host direction, in addition to human leukocyte antigen C and DRB1 mismatches. Three months later, tumor progression occurred from the residual mass in the sacral canal and a new lesion in the pancreas. Although tumor progression could not be controlled by additional chemotherapy and local radiotherapy, the metastatic nodules in bilateral kidneys did not increase in size before his death. To the best of our knowledge, this is the first report of neuroblastoma with bilateral renal metastases in the English medical literature. In addition, this case suggests that the combination of chemotherapy and immunotherapy may inhibit the progression of the renal lesions under certain conditions.

Background and study aims: Primary neoplasms of the small intestine are relatively rare in all age groups, accounting for about 5 % of all gastrointestinal tumors 1. Cavernous hemangiomas of the small intestine are also rare, can cause gastrointestinal bleeding, and are extremely difficult to diagnose preoperatively 2. We present a patient who presented with melena and iron deficiency anemia, for whom wireless capsule endoscopy and single-balloon enteroscopy facilitated the diagnosis of cavernous hemangioma.

Denosumab, a human monoclonal antibody directed against the receptor activator of nuclear factor‑κβ ligand (RANKL), is used for the treatment of patients with metastatic cancer of the bone or osteoporosis. Recent reports have demonstrated that denosumab can induce osteonecrosis of the jaw (ONJ), but reported cases of this are uncommon. The present study reports the case of an 86‑year‑old male with prostate cancer patient exhibiting bone metastases who developed ONJ whilst receiving denosumab. To elucidate the influence of denosumab on the development of ONJ, the present study also reviewed the literature, including clinical trials and case reports. In the clinical trials, the prevalence of denosumab‑related ONJ was higher in patients with cancer compared with those with osteoporosis. The high risk of ONJ in patients with cancer was thought to be associated with the differing dose and frequency of denosumab administration. The prevalence of ONJ was not significantly different between patients receiving denosumab and bisphoshonate (BP). In the reported cases, denosumab‑related ONJ had a similar clinical presentation to BP‑related ONJ. There was also a tendency for denosumab‑related ONJ to develop in the mandible of elderly patients. Previous invasive dental treatment was a commonly shared characteristic of patients with denosumab‑related ONJ. A complex medical history was also suspected to affect the prevalence. No clear association between the dose or duration of denosumab treatment and the development of ONJ was observed. Although conservative treatments are given for denosumab‑related ONJ, non‑improving cases were managed surgically with primarily positive results. Because denosumab may offer superior results compared with BP for the treatment of metastatic cancer of the bone or osteoporosis, the use of denosumab is expected to increase in the near future. Clinicians should also be aware of the risk factors for denosumab‑related ONJ, in order to aid in its diagnosis. In addition, patients treated with denosumab should receive prophylactic treatment to maintain their oral health prior to, during and after denosumab treatment. [ABSTRACT FROM AUTHOR]

Background: The spontaneous rupture of hepatic metastases is rare compared to that of primary hepatic tumors. In addition, vemurafenib, a selective inhibitor of the mutant BRAF protein or gene product, has been reported to be extremely effective in patients with metastatic melanoma who harbor a BRAF V600E mutation. Case presentation: A 44-year-old female had previously undergone surgery for resection of a malignant melanoma in the lower right leg. Four years later, hepatic metastases became apparent, and transcatheter arterial embolization (TAE) was performed. Then she underwent treatment with vemurafenib. The size of the hepatic metastases markedly decreased. Two months later, they enlarged rapidly and ruptured, requiring emergency TAE. However, the patient developed hemorrhagic shock and died of renewed intra-abdominal bleeding on the 26th postoperative day. Conclusions: This is a rare case of ruptured hepatic metastases of malignant melanoma during treatment with vemurafenib. Postmortem examination and immunohistochemical analysis indicated reactivation of the mitogenactivated protein kinase pathway in the metastatic tumor, suggesting secondary resistance to vemurafenib as the possible underlying mechanism. [ABSTRACT FROM AUTHOR]

Abstract

Plexiform schwannoma is a benign peripheral nerve sheath tumor composed exclusively of schwann cells arranged in a plexiform pattern. Most plexiform schwannomas are skin tumors and there has been only one case report of this tumor originating in the colon. We describe herein the first known case of plexiform schwannoma of the small intestine occurring without any relationship to schwannomatosis or neurofibromatosis. A 57-year-old man presented with a short history of abdominal pain, vomiting, and bloody stool after each meal. Jejunography demonstrated multiple nodular tumors in the small intestine. We resected the small intestine laparoscopically. The tumors consisted of multiple white nodules in the submucosal and subserosal layers. Microscopic examination revealed that each tumor was composed mainly of Antony A tissue, compatible with conventional schwannoma. Immunohistochemically, the tumors were positive for S-100, vimentin, and neuron-specific enolase, and negative for HHF35, ?-SMA, and c-kit. No evidence of recurrence has been found in 38 months of follow-up. [ABSTRACT FROM AUTHOR]

The article describes the case of a 74-year-old woman with sebaceous carcinoma of the breast. Case highlights include immunohistochemical analysis of estrogen and progesterone receptors, the first case report of breast carcinoma with a predominant sebaceous component described in 1995,and the importance of cytology in distinguishing between sebaceous carcinoma and other clear cell breast carcinomas.

Macrophages in lungs can be classified into two subpopulations, alveolar macrophages (AMs) and interstitial macrophages (IMs), which reside in the alveolar and interstitial spaces, respectively. Accumulating evidence indicates the involvement of IMs in lung metastasis, but the roles of AMs in lung metastasis still remain elusive. An i.v. injection of a mouse hepatocellular carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5-lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the numbers of metastatic foci, particularly those of a larger size. A major 5-LOX metabolite, LTB4, augmented in vitro cell proliferation of human HCC cell lines as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited higher expression levels of the 5-LOX and LTB4 than IMs. Consistently, 5-LOX-expressing AMs increased in the lungs of human HCC patients with lung metastasis, compared with those without lung metastasis. Furthermore, intratracheal clodronate liposome injection selectively depleted AMs but not IMs, together with reduced LTB4 content and metastatic foci numbers in this lung metastasis process. Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood-borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute to the progression of lung metastasis by providing a potent arachidonic acid-derived tumor growth promoting mediator, LTB4. [ABSTRACT FROM AUTHOR]