[Efficacy of nivolumab in combination with chemotherapy after radiotherapy for meningeal carcinomatosis in patients with Epstein-Barr virus-associated gastric cancer:a case report].

A 62-year-old man presented with fever and anorexia since July X. Initial treatments were rendered ineffective, and due to altered consciousness and vomiting, he was referred to our hospital. On admission, he manifested delirium, drowsiness, and disorientation. While blood tests were normal, gastroscopy identified a type 3 tumor in his lower gastric body, later diagnosed as a poorly differentiated adenocarcinoma. Immunohistochemistry demonstrated negative human epidermal growth factor receptor 2 and positive programmed death-ligand 1 expression with a combined positive score ≥5. Furthermore, a positive Epstein-Barr virus-encoded small RNA in situ hybridization result was noted. Abdominal contrast-enhanced CT and PET-CT scans demonstrated multiple lymph node metastases around the stomach and liver, establishing the diagnosis of stage IVB gastric cancer (T4aN2M1). Brain magnetic resonance imaging (MRI) demonstrated enhanced lesions in the brainstem, cerebellar sulci, and right occipital lobe. Although cerebrospinal fluid cytology was negative for malignancy, the clinical symptoms and MRI findings confirmed leptomeningeal carcinomatosis (LMC). The patient underwent radiotherapy for LMC (total of 30Gy in 10 fractions), followed by combination therapy with a nivolumab and SOX regimen. Posttreatment, the LMC symptoms resolved;however, he experienced grade 3 immune-related adverse events related to liver dysfunction. Nivolumab was discontinued, and with steroid administration, the adverse events improved. Imaging evaluations posttreatment showed gastric tumor reduction and the absence of LMC. After 7 cycles, nivolumab was reintroduced, with no liver dysfunction recurrence noted through 15 cycles. Endoscopic examination 1 year postonset demonstrated that the gastric tumor had scarred, and MRI showed no signs of LMC recurrence. In 5-8% of solid tumors, LMC complications are present, resulting in limited treatment options and poor prognosis. Recent reports suggest the potential of immune checkpoint inhibitors in treating intracranial metastasis from solid tumors. In Japan, nivolumab was approved for gastric cancer treatment in 2017 and for first-line therapy in combination with chemotherapy since 2021. We report a case in which radiotherapy and chemotherapy combined with nivolumab provided durable control of LMC originating from gastric cancer for more than 1 year.

Rhabdomyosarcoma arising from retroperitoneal teratoma in an infantile neurofibromatosis type 1 patient.

We herein report the case of a 2-year-old girl with neurofibromatosis type 1 (NF1), who presented with a 12-cm mass in the right retroperitoneum and underwent tumor resection. Histologically, the tumor was composed of two distinct components: one was teratoma, showing mature morphology; and the other was embryonal rhabdomyosarcoma. An interphase fluorescence in situ hybridization (FISH) analysis of the rhabdomyosarcoma component revealed the absence of isochromosome 12p. Although it is well known that rhabdomyosarcoma occurs in infantile NF1, and that rhabdomyosarcoma can arise from teratoma as a somatic-type malignancy, to the best of our knowledge, this is the first case of an infantile NF1 patient, who developed rhabdomyosarcoma within a retroperitoneal teratoma. The absence of chromosome 12p alteration suggests a possibility that the rhabdomyosarcoma occurred due to the NF1 background, not as a somatic-type malignancy of germ cell tumor.

An Autopsy Case of Idiopathic Pleuroparenchymal Fibroelastosis with Left Vocal Cord Paralysis and a Rapid Deterioration without an Acute Exacerbation.

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a generally slow-progressing rare disorder of unknown etiology. The direct cause of death in cases of IPPFE is rarely investigated. We experienced an autopsy case of a Japanese man with IPPFE and found aspiration pneumonia to be the major trigger of death. The individual had left vocal cord paralysis at admission, which may have contributed to aspiration pneumonia, and which probably was affected by the fibrous adhesion of the left apex of the chest wall resulting from IPPFE. The prevention of aspiration pneumonia is important for maintaining the respiratory function, especially in IPPFE patients with repeated pneumothorax.

An autopsy case of peripheral T cell lymphoma occurring in a postpartum woman: a unique case suggesting changes in the immunocharacteristics of lymphoma cells before and after delivery.

BACKGROUND: The occurrence of malignant lymphoma after delivery is an extremely rare event. Although several cases of Hodgkin lymphoma and B cell lymphoma and a few cases of peripheral T cell lymphoma (PTCL) after delivery have been reported, there are no report of autopsy cases of PTCL in the puerperal period. CASE PRESENTATION: A 32-year-old Japanese woman with a past medical history of atopic dermatitis and bronchial asthma presented with generalized eruptions four days after the delivery of her first child; generalized skin induration and lymphadenopathy subsequently emerged. A skin biopsy specimen showed the diffuse proliferation of atypical lymphoid cells that were immunohistochemically-positive for CD4 but negative for CD8. She was diagnosed as PTCL, not otherwise specified (PTCL, NOS). She died one year and three months after the onset of symptoms. At autopsy, the systemic infiltration of lymphoma cells into the whole body was observed. Unexpectedly, these lymphoma cells were immuno-reactive with CD8 but not with CD4. CONCLUSION: The occurrence and development of PTCL after delivery with the shift from CD4 positivity to CD8 positivity may be associated with not only the selection of resistant subclone as a result of chemotherapy but also the changes of immune status before and after delivery.

A case report of infantile cystic nephroblastoma.

BACKGROUND: Nephroblastoma (NB) is a malignant embryonal neoplasm derived from nephrogenic blastemal cells. NB usually forms a solid mass, but in extremely rare cases, it may show cystic changes. CASE PRESENTATION: A six-month-old girl with persistent high fevers was found to have pyuria and bacteriuria. Ultrasonography revealed multilocular cysts in the right kidney. Right nephrectomy was performed with cyst wall rupture during surgery. An intraoperative rapid diagnosis, based on peritoneal fluid cytology, confirmed three components of blastemal, stromal, and epithelial cells. The blastemal cells were dyshesive, with scant to no cytoplasm and were the predominant cell type. The spindle-shaped stromal cells were arranged in fascicles. The epithelial cells demonstrated tubular structures. Macroscopically, the resected cystic tumor measured 80 mm in maximum diameter with a prominently thin cyst wall, but solid areas were also apparent. Histologically, the tumor was diagnosed as cystic NB (blastemal-predominant) displaying a triphasic pattern. Hyperchromatic nuclei and apoptotic bodies were found. The clinical stage classification of Japan Wilms Tumor Study group was 3. The patient was treated with chemotherapy and radiotherapy. Tumor recurrence and metastasis have not been observed in the 8 months since surgery. CONCLUSION: This is an extremely rare case of infantile cystic NB. We diagnosed the NB cells that appeared in the peritoneal fluid by intraoperative rapid cytology. Cytological examination proved to be a very useful technique for determining the clinical stage of NB. Additionally, we propose that massive tumor degeneration and necrosis be considered as a pathogenic mechanism of cyst formation in NB.

The clinicopathological comparison among nodal cases of idiopathic multicentric Castleman disease with and without TAFRO syndrome.

Multicentric Castleman disease (MCD) is a systemic inflammatory disease potentially caused by an increase in the serum interleukin-6 (IL-6) level. Idiopathic MCD (iMCD) is histopathologically classified into three types: plasmacytic (PC), mixed, and hypervascular (hyperV) types. Recently, a unique clinical phenotype with a poor prognosis overlap with iMCD, thrombocytopenia, anasarca, fever, renal failure or reticulin fibrosis, and organomegaly (TAFRO syndrome), has been reported from Japan, but its detailed clinicopathological features remain unclear. In this study, we performed a clinicopathological analysis of 70 nodal cases of iMCD with and without TAFRO syndrome (n = 37 versus n = 33). Compared with iMCD without TAFRO, iMCD with TAFRO showed more atrophic lymphoid follicles (LF), greater distances between follicles, increased glomeruloid vascular proliferation within the germinal center, and increased follicular dendritic cells. In addition, the hyperV type in particular demonstrated severe atrophic LF and interfollicular vascular proliferation. Among the mixed-type cases, the serum IL-6 levels in iMCD with TAFRO were significantly higher than those in iMCD without TAFRO. Furthermore, compared to iMCD without TAFRO, the numbers of immunoglobulin G4 (IgG4)-positive and CD38-positive plasma cells were significantly decreased in iMCD with TAFRO.