Leptomeningeal carcinomatosis (LC) is a rare but deleterious complication of solid malignancies, which is exceedingly uncommon in cervical cancer. Although advancements in multimodal therapy have prolonged survival in patients with advanced cervical cancer, involvement of the central nervous system, including LC, is being increasingly recognized and is associated with an extremely poor prognosis. Ante-mortem diagnosis remains challenging because of nonspecific neurological manifestations and the limited sensitivity of currently available diagnostic modalities. Herein, we report a case of a 47-year-old woman with cervical adenosquamous carcinoma who developed rapidly progressive neurological symptoms during treatment for recurrent disease. She initially presented with lower limb weakness and diplopia, followed by rapid deterioration, including dysarthria, quadriparesis, central diabetes insipidus, and impaired consciousness. Contrast-enhanced magnetic resonance imaging of the brain and spine revealed no definitive abnormalities, and cerebrospinal fluid cytology showed only atypical cells, without conclusive evidence of malignancy. Despite inconclusive findings, LC was clinically suspected based on the overall disease course, and whole-brain radiotherapy was initiated. The patient’s neurological condition worsened, and she died 36 days after the onset of neurological symptoms. Autopsy revealed extensive leptomeningeal dissemination of cervical cancer extending from the cervical spinal cord to the cauda equina. Collectively, this autopsy-confirmed case illustrates the aggressive and often fatal clinical course of LC arising from cervical cancer and suggests substantial diagnostic difficulty in the ante-mortem diagnosis, contributing to the limited literature on this rare entity.
Human chorionic gonadotropin (hCG)-producing invasive urothelial carcinoma is a rare entity with no established standard treatment. A 48-year-old man presented with gross hematuria, weight loss, and elevated serum hCG (5,291 mIU/mL). Cystoscopy revealed a prostatic urethral tumor, while computed tomography demonstrated multiple intra-abdominal and pelvic lymph node metastases, alongside liver and ilium involvement. Histopathological examination confirmed highly atypical urothelial carcinoma invading the prostate with ectopic syncytiotrophoblastic cells, which were immunohistochemically positive for hCG. The patient was diagnosed with metastatic urothelial carcinoma with trophoblastic differentiation (pT4aN3M1b) and commenced enfortumab vedotin plus pembrolizumab treatment. After seven treatment cycles, his serum hCG normalized to < 1.0 mIU/mL, and imaging showed marked shrinkage of all metastatic lesions. The patient’s treatment was ongoing at the last follow-up. This rare metastatic hCG-producing urothelial carcinoma case demonstrated a dramatic response to combined enfortumab vedotin and pembrolizumab therapy.
Multiple primary malignant tumors are rare, synchronous, and advanced, presenting therapeutic challenges but potentially remain curable. However, standardized treatment strategies have not yet been established. The patient was a 63-year-old man who was diagnosed with synchronous multiple primary malignant tumors comprising stage IIIB lung adenocarcinoma (with programmed-death ligand 1 protein expression of 75
Dedifferentiated liposarcoma (DDLPS) is a high-grade soft tissue sarcoma that has shown resistance to conventional multimodal therapies. We present the case of a 69-year-old Japanese man with DDLPS in whom an NTRK1::POU2F1 rearrangement was detected. He presented with a third recurrence of a soft tissue tumor near the right clavicle, initially misdiagnosed as desmoid fibromatosis and later re-diagnosed as pleomorphic sarcoma. Histopathological evaluation showed nuclear immunopositivity for murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4), and the tumor was finally diagnosed as DDLPS. As multiple pulmonary and lymph node metastases were present, multidisciplinary therapy was initiated. Radiotherapy was administered to the locally recurrent tumor in the right clavicular region. Following radiotherapy and three cycles of doxorubicin monotherapy, the pulmonary metastases showed slight enlargement, although the overall response remained stable disease (SD). Cancer genomic profiling (CGP) identified an NTRK1::POU2F1 rearrangement along with amplifications of MDM2 and CDK4. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was introduced as a targeted therapy (200 mg/day). Stable disease was observed at three months. However, subsequent imaging at six months showed disease progression, prompting a switch to eribulin. Additional pan-TRK immunohistochemistry was negative in both the initial and recurrent resection specimens. The direct fusion product predicted from the CGP-reported rearrangement would lack the NTRK1 kinase domain. No clear antitumor effect of larotrectinib could be established. These findings highlight the importance of evaluating the structure and expression of atypical NTRK rearrangements before considering them actionable therapeutic targets in DDLPS.
Neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive malignancy characterized by rapid progression and poor prognosis. Although platinum-based chemotherapy, particularly etoposide combined with cisplatin or carboplatin, is commonly adopted based on treatment strategies for small-cell lung cancer, most patients experience disease relapse, and durable disease control remains difficult to achieve. Furthermore, optimal treatment strategies after successful platinum-based chemotherapy have not been established, and maintenance approaches for NEPC have rarely been reported. Recent advances in genomic profiling have identified homologous recombination repair (HRR) gene alterations, including BRCA2 abnormalities, in a subset of aggressive prostate cancers. While Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated clinical benefit in HRR-deficient metastatic castration-resistant prostate cancer, their role in NEPC remains unclear because these patients have been largely excluded from pivotal clinical trials. We herein report a unique case of de novo metastatic large-cell neuroendocrine carcinoma of the prostate harboring a homozygous BRCA2 deletion, in which a marked response to platinum-based chemotherapy was followed by sustained disease control during olaparib maintenance therapy. This case supports further investigation of PARP inhibition as a maintenance strategy in selected patients with BRCA2-altered NEPC.
