Pulmonary sclerosing pneumocytoma mimicking a low-grade primary malignancy: A case report.

INTRODUCTION: Pulmonary sclerosing pneumocytoma (PSP) is a rare benign tumor classified as a pulmonary adenoma. It presents as a solitary pulmonary nodule without any specific findings, often posing a diagnostic challenge. We herein present a case of a PSP with a short volume doubling time (VDT) comparable to low-grade pulmonary malignancies. CASE PRESENTATION: A 27-year-old female presented to the emergency department with a fever that had persisted for the past two days. An incidental finding on chest screening computed tomography (CT) revealed a 9 mm pulmonary nodule with a round shape and smooth margin, suggestive of a benign etiology. Follow-up CT one year later revealed an enlarged nodule exhibiting a VDT of 249 days. A thoracoscopic lingulectomy was performed, and the histopathological examination revealed papillary and diffuse proliferation of epithelial-like cells. The epithelial cells were positive for cytokeratin (CKAE1/AE3) and thyroid transcription factor 1 (TTF1), whereas the stromal cells were positive for TTF1 but negative for CKAE1/AE3. Those results were consistent with the diagnosis of a PSP. DISCUSSION: PSPs typically present as incidental pulmonary nodules with no specific findings, often posing a diagnostic challenge. The radiographic features of PSPs have mainly been explored based on the morphological findings and metabolic activity, with limited research on their growth rate, represented by the VDT. CONCLUSION: PSPs may exhibit rapid growth, demonstrating a short VDT similar to that of low-grade pulmonary malignancies. Comprehensive diagnostic testing not based solely on the growth rate for this rare condition is essential.

A solitary pulmonary nodule in a former glass blower mimicking a primary lung adenocarcinoma.

INTRODUCTION: Inhalation of silicon dioxide causes silicosis, a condition that may occur in various industries and work settings. Radiologic findings typically show numerous nodular opacities, while solitary pulmonary nodules are atypical for silicosis. PRESENTATION OF CASE: A 68-year-old woman, a former glassblower, presented with a left solitary pulmonary nodule (13 mm) on chest computed tomography. The nodule enlarged to 23 mm over 6 months, exhibiting an irregular shape, spiculated margin, and rapid growth with a doubling time of 186.4 days. She underwent a left upper lobectomy with a suspicion of lung cancer. The histopathological findings revealed peribronchial lymphocytic infiltration and granulomatous-like structures containing multinucleated giant cells and phagocytic crystalline foreign bodies. These findings were consistent with a foreign body reaction to the glass fragments. DISCUSSION: Inhaled glass fragments may present as a solitary pulmonary nodule after the retirement of a glass blower. Its behavior and radiological features mimicked a primary lung adenocarcinoma. CONCLUSION: Solitary pulmonary nodules due to inhaled glass fragments may mimic a primary lung adenocarcinoma. A definitive diagnosis requires a histological examination in this rare condition.

An Adult Case of Idiopathic Pulmonary Hemosiderosis Associated with Pulmonary Fibrosis and Emphysematous Change.

A 48-year-old woman was admitted to our hospital with acute respiratory failure. Chest computed tomography showed ground-glass opacity and patchy emphysematous lesions in both lungs. Corticosteroid therapy was effective; however, the disease worsened with the tapering of corticosteroids. Bronchoalveolar lavage revealed hemosiderin-laden macrophages, and video-assisted thoracic surgery showed diffuse interstitial fibrosis with diffuse alveolar hemorrhage (DAH). There was no evidence of vasculitis nor autoimmune diseases. This patient was diagnosed with idiopathic pulmonary hemosiderosis (IPH) that progressed to end-stage pulmonary fibrosis despite treatment. Autopsy demonstrated DAH with pulmonary fibrosis and emphysematous change, suggesting IPH-related pulmonary lesions.

A case of adrenal lymphangioma successfully treated with laparoscopic partial adrenalectomy.

Introduction: Adrenal lymphangioma is a rare benign tumor of lymphatic origin, usually incidentally detected from various imaging studies taken for an unrelated purpose. We present a case of a right adrenal lymphangioma treated successfully with surgical intervention. Case presentation: A 36-year-old previously healthy woman was referred to our urology department for a right adrenal mass, discovered during a routine health checkup. The tumor had no endocrinological activity, and the patient opted for surgical resection following a concern for malignancy. A laparoscopic right partial adrenalectomy was performed, and on histological examination, the tumor was diagnosed as right adrenal lymphangioma. Conclusion: Adrenal lymphangiomas lack disease specific radiological characteristics that allow for a definitive diagnosis from imaging alone. To rule out tumors of potentially malignant nature, surgical intervention should be considered.

A case of prostatic metastasis from non-seminomatous testicular cancer.

Introduction: Prostatic metastasis from testicular cancer is extremely rare, with only 10 reported cases, all of which were diagnosed as relapse. Herein, we report the case of a patient with concurrent testicular cancer and prostatic metastasis. Case presentation: A 57-year-old man presented at our emergency department with urinary retention. A painless mass was found in the right scrotum, and computed tomography showed lung, mediastinal, and liver metastases, and an enlarged prostate. Tumor markers were measured in 2057 U/L lactate dehydrogenase, 2460 mIU/mL human chorionic gonadotrophin, 1303 ng/mL alpha-fetoprotein, and 1.51 ng/mL prostate specific antigen. An orchiectomy and biopsy were performed; the pathological results showed immature teratomas, embryonal carcinomas, choriocarcinomas, and seminomas in the testis, and embryonal carcinomas in the prostate, liver, and mediastinum. The patient refused chemotherapy and died 3 months following diagnosis. Conclusion: Prostatic metastasis should be considered in cases of dysuria or prostate enlargement in testicular cancers.

Evaluation of the widths of the mucosal strips in pathological examination of specimens of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer in Japan. Pathological evaluation of ESD specimens is considered essential to determine if additional gastrectomy is necessary. Usually, specimens resected by ESD are sliced into 2-3 mm wide sections, and each section is examined for depth of tumor and lymphovascular invasion. Nevertheless, in most cases of additional gastrectomy, lymph node metastasis is not present. Given that there are few-studies on how clinical-decisions based on the pathologic-evaluation-method, in particular the specimen cut-width, influence patient outcomes, we retrospectively evaluated whether reducing the number of cuts to one-half or one-third would result in underestimation of the real need for additional surgery. The effect of the actual cut-width on recommended treatment (referral to operation) and patient-outcomes was also assessed. METHODS: Pathological records of 498 lesions from 439 patients were reviewed and re-evaluated. All pathological descriptions are based on the gastric cancer classification system of the Japanese Gastric Cancer Association, 15th edition. RESULTS: In 5.8% and 8.5% of the total specimens, underdiagnosis of tumor-depth and lymphovascular invasion occurred when the number of sections was reduced to one-half and one-third, respectively. Significantly more submucosal invasions were found in the group in which the cut-with was between 3 and 4 mm than in the group in which the cut width was less than 3 mm. CONCLUSION: Evaluation of the appropriate cut-width is important and should be discussed from the standpoint of labor costs and lost opportunities to search for molecular markers in ESD materials.

New-onset of eosinophilic granulomatosis with polyangiitis without eosinophilia and eosinophilic infiltration under benralizumab treatment: A case report.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small- to medium-vessel necrotising vasculitis and eosinophilic inflammation. Mepolizumab, an anti-interleukin-5 (IL-5) monoclonal antibody has been approved in Japan since 2018 for refractory EGPA treatment. Benralizumab, an anti-IL-5 receptor monoclonal antibody, also has been reported to reduce the glucocorticoid dose in patients with refractory EGPA. On the other hand, several investigators have demonstrated new-onset EGPA under biologics, and it is unclear whether this treatment for severe allergic diseases can prevent the development of EGPA. Herein, we report a case of new-onset EGPA under benralizumab treatment. The patient had fever, weight loss, muscle pain, and paraesthesia, the serum eosinophil count was 0/µL, and the biopsy showed necrotizing vasculitis without eosinophilic infiltration. She was diagnosed as having EGPA and treated with high-dose glucocorticoid and intravenous cyclophosphamide, with a good response. Our case report indicates that anti-IL-5 agents may mask the development of EGPA and clinicians should be aware of the development of EGPA during anti-IL-5 agents.

Promising Therapeutic Impact of Immune Checkpoint Inhibitors in Type II Endometrial Cancer Patients with Deficient Mismatch Repair Status.

Type II endometrial cancer (EC) is responsible for most endometrial cancer-related deaths due to its aggressive nature, late-stage detection, and high tolerance to standard therapies. Thus, novel treatment strategies for type II EC are imperative. For patients with mismatch repair-deficient (dMMR) tumors, immunotherapy with immune checkpoint inhibitors represents a promising therapeutic strategy. However, the prevalence of dMMR tumors in type II EC patients remains unclear. In this study, using immunohistochemistry, we evaluated the expression of mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1) in 60 patients with type II EC (16, 5, 17, and 22 were endometrioid G3, serous, de-differentiated, and carcinosarcoma cases, respectively) to investigate the therapeutic effect of immune checkpoint inhibitors. Approximately 24 cases (40%) had a loss of MMR protein expression. The positivity rate of CD8+ (p = 0.0072) and PD-L1 (p = 0.0061) expression was significantly associated with the dMMR group. These results suggest immune checkpoint inhibitors (anti-PD-L1/PD-1 antibodies) could effectively treat type II EC with dMMR. The presence of dMMR might be a biomarker for a positive response to PD-1/PD-L1 immunotherapy in type II EC.

Elective video-assisted thoracic surgery for a ruptured mature mediastinal teratoma: A case report.

INTRODUCTION AND IMPORTANCE: Mature mediastinal teratomas can rarely become symptomatic after a compression of surrounding organs and a rupture and are often treated with an emergency open approach such as median sternotomy. Clinical significance of thoracoscopic approach as elective setting is unknown. CASE PRESENTATION: A previously healthy 21-year-old man presented with worsening left-sided chest pain for one week. Chest computed tomography revealed a multilocular cystic mass with no evidence of great vessel invasion. A histopathological examination of the biopsy specimen revealed that the pancreatic glands and ductal elements were without any immature embryonic tissue, consistent with a mature teratoma. After the symptoms improved, he successfully underwent an elective video-assisted thoracic surgery as a substitute for an emergency median sternotomy. CLINICAL DISCUSSION: The ectopic pancreatic tissue itself may not imply an emergency surgery and a comprehensive workup is essential for an optimal treatment strategy. Elective surgery is worthy of consideration as a therapeutic option. CONCLUSION: Elective video-assisted thoracic surgery could be a feasible option even for a ruptured mature mediastinal teratoma in selected patients. Besides its maximum size, a large proportion of the cystic component and the absence of great vessel invasion may indicate the feasibility of a video-assisted thoracic surgery.

Cytological study of 44 cases with solid papillary carcinoma and a systemic review of solid papillary carcinoma and neuroendocrine tumor of the breast.

BACKGROUND: Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies. METHODS: We examined 44 cases of SPC of the breast to define the cytologic features. We also made a systemic review of reported cases of SPC and neuroendocrine tumor (NET) of the breast. RESULTS: Both of our and the reviewed cases with SPC were very similar in the cytologic finding. It included hypercellularity, highly discohesive clusters, numerous isolated cells, small nuclei, finely granular chromatin of salt-and-pepper appearance, inconspicuous nucleoli, low nuclear-cytoplasmic ratio, and a plasmacytoid appearance. Moreover, SPC and NET had frequently all of these features in common. Capillary vessels structures and mucinous substance were not frequently seen in our and the reviewed cases with SPC. Rosette and pseudorosette were very rare in the cytologic specimen. The immunocytochemistry with our 9 cases with SPC indicated diffuse positivity for chromogranin A and/or synaptophysin. CONCLUSION: Many cytologic features are frequently shared by SPC and NET of the breast. However, the vascular structure may not be a precise criterion for SPC. Rosette and pseudorosette are rarely helpful for the cytologic diagnosis.

A large-scale clinicopathological and long-term follow-up study of solid papillary carcinoma of the breast.

Solid papillary carcinoma of the breast (SPC) is a rare tumor of the breast with the unique histology and frequent neuroendocrine differentiation. However, a real nature and diagnostic importance of the neuroendocrine differentiation have not been properly handled. And relationship between SPC and the other types of invasive breast carcinoma, especially neuroendocrine tumor of the breast (NETb), has not been fully explained. We conducted a clinicopathological study of SPC to tackle these problems.In the study, we included 127 cases of SPC with long-term follow-ups of up to 30 years. The incidence in the breast carcinoma was 2.0%. The patients with SPC had a significantly better prognosis and no patients died of the tumor. The 35 cases had only SPC in situ (SPC-IS), while the 92 cases had both SPC-IS and SPC with invasion (SPC-INV). Immunohistochemically, 123 of the 127 cases exhibited diffuse expression of one or more neuroendocrine markers. Fifty of the 92 cases had exclusively invasive SPC (iSPC) as the invasive component. Twenty-two cases of iSPC were combined with NETb and the 18 cases with MUC. Six of 8 cases with metastatic SPC-INV disclosed iSPC in the axillary lymph node.This study suggests that SPC is immunohistochemically compatible with NET of the systemic organs (NETs). And the unique morphology of SPC may represent a traditional histology of NETs. The study also indicates that SPC has close relationship between NETb and type B MUC. And SPC and NETb may represent a spectrum of the same disease.

Spontaneous transient size reduction of a solitary pulmonary metastasis from a leiomyosarcoma.

BACKGROUND: A solitary pulmonary nodule (SPN) poses a diagnostic challenge, which includes both a benign and malignant etiology. A size enlargement often indicates malignancy. We herein describe a case of a solitary pulmonary metastasis from a leiomyosarcoma that regressed transiently during follow-up. CASE PRESENTATION: A 47-year-old woman presented with an SPN detected by follow-up computed tomography 7 years after surgery for a left forearm high-grade leiomyosarcoma. The nodule regressed spontaneously after an additional 6 months, and therefore, an inflammatory change was the most likely diagnosis at that time. However, the nodule enlarged again over the next 5 years. The growth rate led us to suspect a malignancy. A trans-bronchial biopsy was undiagnostic and a video-assisted thoracic surgery was planned. She underwent a wedge resection of the right lung, and a histopathological examination found it was a metastatic leiomyosarcoma. CONCLUSIONS: A pulmonary metastasis from a leiomyosarcoma could emerge as an SPN and reveal a subsequent transient size reduction. An SPN in patients even with a remote history of a soft tissue tumor should raise the possibility of metastasis, and periodic follow-up is essential even after the size reduction.

Testicular teratomagenesis from primordial germ cells with overexpression of germinal center-associated nuclear protein.

Testicular teratomas are the major histologic type of testicular germ cell tumors and their incidence continues to grow. Moreover, teratomas can develop from undifferentiated cells in induced pluripotent stem (iPS) cell transplantation therapy, seriously hampering the progress of regenerative medicine. Germinal center-associated nuclear protein (GANP) is thought to be important to the biogenetic control of primordial germ cells and is among the genes susceptible to testicular germ cell tumors. Thus, we analyzed the expression of GANP in human testicular postpubertal-type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis. We analyzed 31 cases of human testicular postpubertal-type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ accompanied by the teratoma. GANP expression was particularly high in the epithelia of the epidermis, cutaneous appendages, and trachea-like ciliated epithelium. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG-ganpTg mice). In the GANP-teratoma mice, GANP-overexpressing teratomas were more frequent at the testes and the middle portion of the uterus than has been seen in the previously established mouse models. In conclusion, GANP is overexpressed in testicular postpubertal-type teratomas and is an essential teratomagenic factor. We also found that CAG-ganpTg mice are useful mouse models of teratomagenesis that mimics human midline teratomas and that teratomas may originate from the overexpression of GANP in primordial germ cells.

Intra-abdominal Hemorrhage Due to Splenic Vein Aneurysm Rupture Caused by Invasive Aspergillosis during Treatment for Advanced Non-small-cell Lung Cancer.

A 71-year-old man was admitted for left-sided chest pain. He had a history of diabetes, treatment with epidermal growth factor receptor-tyrosine kinase inhibitor for advanced non-small-cell lung cancer, and corticosteroid treatment for underlying lung diseases. Chest computed tomography showed consolidations in the bilateral lower lobes, and Aspergillus fumigatus was detected by bronchoscopy. Invasive pulmonary aspergillosis was suspected, and antifungal therapy with voriconazole was initiated; however, the patient passed away suddenly. Autopsy revealed disseminated Aspergillus infection and intra-abdominal hemorrhage due to the rupture of a splenic vein aneurysm caused by Aspergillus necrotizing vasculitis, which was considered the cause of death.

Successful switching treatment of adalimumab for refractory pyoderma gangrenosum in a patient with rheumatoid arthritis with prior use of tumour necrosis factor inhibitors: A case report and review of the literature.

Pyoderma gangrenosum (PG) is a rare chronic skin disease characterised by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumour necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG 2 months after orthopaedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of other tumour necrosis factor inhibitors.

Medium-vessel Vasculitis Presenting with Myalgia Following COVID-19 Moderna Vaccination.

Coronavirus disease 2019 (COVID-19) vaccines have been delivered worldwide to prevent the spread of the disease, and almost all Japanese have received the mRNA vaccines "BNT162b2" (Pfizer-BioNTech) or "mRNA-1273" (Moderna). These vaccines have shown efficacy and safety with only minor adverse drug reactions. However, some patients develop severe adverse drug reactions, including autoimmune reactions. In addition, systemic vasculitis, mainly small-vessel vasculitis, following COVID-19 vaccination, has been reported. However, only a few investigators have reported medium-vessel vasculitis following vaccination. We herein report a case of medium-vessel vasculitis presenting with myalgia as the initial clinical manifestation following COVID-19 Moderna vaccination.

Sudden hemothorax as a rare initial manifestation of bronchiectasis under a direct oral anticoagulant.

BACKGROUND: A hemothorax as the initial manifestation of bronchiectasis is extremely rare. We report a case of a sudden hemothorax due to exacerbation of clinically latent bronchiectasis under a direct oral anticoagulant. CASE PRESENTATION: A 77-year-old woman presented with chest pain and a fever noted since the day before. She had stage G3 chronic kidney disease and received edoxaban for paroxysmal atrial fibrillation. She had no history of trauma or respiratory symptoms. A chest computed tomography revealed a mass with a surrounding opacity in the right lower lobe with a pleural effusion. Conservative treatment was chosen because of the stable vital signs and her respiratory condition. Her oxygen saturation dropped 7 h later with progressive anemia. Repeated chest computed tomography showed a worsening pulmonary opacity and pleural effusion. She underwent a right lower lobectomy successfully. The histopathological findings suggested that the preceding infection of the subpleural focal bronchiectasis caused the bleeding. In addition, a steep caliber change between the subpleural focal bronchiectasis and proximal normal branch may have caused an intraluminal pressure gradient resulting in a peripheral discharge causing a pleural rupture with a hemothorax. CONCLUSION: The sudden hemothorax could have been the initial manifestation of bronchiectasis. Particular attention should be paid to peripherally localized bronchiectasis even if it is without any clinical symptoms, especially in patients with a comorbidity such as a susceptibility to infections and the use of direct oral anticoagulants.

Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines.

Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.

Mutation Profiles of Ovarian Seromucinous Borderline Tumors in Japanese Patients.

Ovarian seromucinous tumors (SMBTs) are relatively rare, and their carcinogenesis is largely unknown. In this study, the molecular features of SMBTs in Japan are assessed. DNA was extracted from microdissected paraffin-embedded sections from 23 SMBT cases. Genetic mutations (KRAS, BRAF, PIK3CA, and ERBB2) were evaluated using Sanger sequencing. Immunohistochemistry for p53, ARID1A, and PTEN was also performed as a surrogate for the loss of functional mutations in these tumor suppressor genes. The prevalence of KRAS, BRAF, PIK3CA, and ERBB2 mutations was 4.3% (1/23), 8.6% (2/23), 8.6% (2/23), and 17.3% (4/23), respectively. Overexpression or loss of p53 expression occurred in 26% (6/23), loss of ARID1A expression in 4.3% (1/23), and none of the cases showed expression of PTEN loss. These findings suggest that KRAS/BRAF/PIK3CA and PTEN mutations are rare carcinogenic events in SMBTs. The high frequency of positive p53 staining and a low frequency of loss of ARID1A staining suggests that SMBT carcinogenesis may be related to the alteration of p53 rather than that of ARID1A. ERBB2 oncogenic mutations may play an important role in the tumorigenesis of Japanese SMBTs.

Ovarian Endometrioid and Clear Cell Carcinomas with Low Prevalence of Microsatellite Instability: A Unique Subset of Ovarian Carcinomas Could Benefit from Combination Therapy with Immune Checkpoint Inhibitors and Other Anticancer Agents.

Ovarian cancer has the highest mortality rate among all gynecological malignancies; therefore, a novel treatment strategy is needed urgently. Utilizing immune checkpoint inhibitors has been considered for microsatellite instability (MSI)-high (MSI-H) tumors. However, the prevalence of MSI-H tumors in ovarian endometrioid and clear cell carcinomas remains unclear. Here, polymerase chain reaction was used to analyze 91 cases of ovarian endometrioid and clear cell carcinomas for the MSI status and the relationship between MSI-H, immune checkpoint molecules, and clinicopathological factors (including patient survival). Only 5 of 91 (5%) cases were MSI-H endometrioid carcinomas. In these cases, CD-8 expression was significantly higher (p = 0.026), confirming an enhanced immune response. From the survival curve, no statistical correlations were found between the MSI-H group and the microsatellite stable (MSS) group; however, the MSS group trended towards better progression-free survival than the MSI-H group (p = 0.056). Patients with PD-L1 expression had shorter overall survival than those without (p = 0.022). Thus, MSI-H is a rare event and not a favorable prognostic factor in ovarian endometrioid and clear cell carcinomas. Thus, to improve the prognosis of ovarian endometrioid carcinoma and clear cell carcinomas, a combination therapy of immune checkpoint inhibitors and other molecular targeted therapies may be required.