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NAKANISHI TakaakiUniversity Hospital / Diagnostic PathologyAssistant Professor
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■ Paper- Herein, we present the case of a 67-year-old woman who presented with a 14-month history of progressive lower limb paresthesia and muscle weakness. Bilateral sensorineural hearing loss also developed during the disease course. Six months prior to admission, cerebrospinal fluid cytology revealed findings suspect of malignancy. Although tumor screening was performed, the cause could not be identified. Due to symptom progression, the patient was re-admitted after which further examination revealed invasive lobular carcinoma of the left breast as the primary tumor, with further metastasis to the large intestine also confirmed. Immunostaining of the cerebrospinal fluid revealed cells with positive findings for estrogen receptor (ER) and AE1/3, leading to a definitive diagnosis of meningeal dissemination. This was a rare case of meningeal dissemination of breast cancer, initially presenting with slowly progressive cauda equina syndrome. This case highlights the importance of repeated tumor screening for neurological symptoms of unknown primary origin.May 2026, Rinsho shinkeigaku = Clinical neurology, 66(5) (5), 309 - 313, Japanese, Domestic magazineScientific journal
- Cancer-associated fibroblasts (CAFs) in the esophageal squamous cell carcinoma (ESCC) microenvironment promote cancer progression through cell-cell interactions with cancer cells. A method has been established to generate CAF-like cells by direct co-culturing human bone marrow-derived mesenchymal stem cells (MSCs), a known source of CAFs, with ESCC cells. Using this method, cDNA microarray analyses were conducted on monocultured and co-cultured ESCCs or MSCs. In this study, bone marrow stromal cell antigen 2 (BST2) was studied, which is remarkably expressed in both ESCC cells and CAF-like cells after co-culture and may contribute to cell-cell interactions. In a public database of single-cell RNA-sequencing data from ESCC tissues, BST2 was markedly expressed in cancer cells and CAFs, and the results strongly suggested an interaction between CAFs and BST2-expressing cancer cells. The co-cultured ESCC cells and CAF-like cells showed enhanced proliferation, migration, and adhesion via the extracellular signal-regulated kinase signaling pathway, and BST2 was involved in these phenotypes. Furthermore, BST2 contributed to adhesion between MSCs and ESCC cells in direct co-culture. Immunohistochemistry demonstrated that high BST2 expression, especially in the cancer stroma, was significantly associated with adverse clinicopathologic factors and poor prognosis in patients with ESCC. In conclusion, BST2 contributes to ESCC progression by facilitating cell-cell interactions between cancer cells and CAFs within the tumor microenvironment.May 2026, The American journal of pathology, 196(5) (5), 1220 - 1243, English, International magazineScientific journal
- Esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis due to aggressive invasion and therapy resistance. Cancer-associated fibroblasts (CAFs) are key stromal components that promote tumor progression; however, their specific roles in ESCC remain unclear. Using a direct co-culture model of ESCC cell lines (TE-9, -10, and -15) and mesenchymal stem cells (MSCs) to generate CAF-like cells, we identified biglycan (BGN) as a significantly upregulated gene in CAF-like cells via cDNA microarray analysis. Public single-cell RNA sequencing data also demonstrated elevated BGN expression in CAF clusters. We confirmed that CAF-like cells exhibited elevated BGN expression and secretion at both the mRNA and protein levels. Recombinant human BGN enhanced ESCC cell proliferation and migration by activating Erk and NF-κB signaling pathways, effects abrogated by TLR4 blockade. Furthermore, BGN promoted CAF marker expression in MSCs, M2-like macrophage polarization, and enhanced proliferation and migration abilities in both cell types. Immunohistochemical analysis of 66 ESCC tissues revealed that high stromal BGN expression correlated with greater tumor invasion, lymphatic invasion, and shorter disease-free survival. These findings indicate that CAF-derived BGN promotes ESCC progression via TLR4-mediated signaling and modulates stromal cell behavior, highlighting its potential as a prognostic biomarker and therapeutic target.Dec. 2025, International journal of molecular sciences, 26(24) (24), English, International magazineScientific journal
- UNLABELLED: Patients with advanced nodal involvement (cN2 or cN3) in urothelial carcinoma (UC) typically have poor outcomes after radical surgery. Clinical evidence on how to manage these patients following immunotherapy is limited. Major neoadjuvant trials such as KEYNOTE-B15 and NIAGARA excluded patients with multiple or bulky nodal metastases, leaving a significant gap in evidence. We present a case of a 76-year-old man with cT1 bladder cancer, concomitant distal ureteral UC (≤ cT2), and multiple enlarged right pelvic lymph nodes (cN2). After six cycles of enfortumab vedotin plus pembrolizumab (EVP), he achieved a radiologic complete response (CR) and resolution of hydronephrosis. He then underwent robot-assisted right nephroureterectomy with extended pelvic lymph node dissection using the da Vinci Xi surgical system. Pathology revealed no residual cancer in either the primary site or lymph nodes (ypT0, ypN0), with marked fibrosis suggesting a strong treatment response. There were no surgical complications, and systemic therapy was stopped after surgery. To our knowledge, this is the first reported case of pathologic complete response following EVP and robotic nephroureterectomy in a patient with node-positive UC. This case supports the potential role of surgery in select patients with excellent responses to systemic therapy who were initially considered unresectable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-025-00785-8.Oct. 2025, International cancer conference journal, 14(4) (4), 407 - 411, English, International magazineScientific journal
- Metastatic upper tract urothelial carcinoma (mUTUC) often has poor prognosis. While systemic therapy is the standard care for mUTUC, lymph node dissection (LND) combined with radical nephroureterectomy (RNU) can be considered for patients with only clinical locoregional LN, resulting in a surgical cure. However, since pembrolizumab, an anti-PD-1 monoclonal antibody, was approved for mUTUC patients, prognosis of mUTUC has been improved and some patients with immune-related adverse events have experienced a clinical complete response and a long-lasting therapeutic response without surgery. Thus, clarifying the optimal patient selection and timing for RNU + LND is warranted to avoid unnecessary surgery. We herein report the first unique case with a clinical N + UTUC patient who underwent RNU plus LND and showed a pathological complete response after discontinuation of pembrolizumab due to adrenal insufficiency. We feel that our case may affect the treatment strategy for N + UTUC in the era of ICIs.Oct. 2024, International cancer conference journal, 13(4) (4), 391 - 394, English, International magazineScientific journal
- Bowen's disease (BD), also known as squamous cell carcinoma (SCC) in situ, is a precancerous skin condition that can potentially progress to invasive tumors. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor typically found in sun-exposed areas of elderly Caucasians. The coexistence of BD and MCC is extremely rare, particularly when MCC is located in subcutaneous tissue rather than its typical epidermal or dermal layers. This case report presents an unusual instance of BD coexisting with subcutaneous MCC on the dorsum of the hand in an elderly Japanese male. An 87-year-old Japanese male with over 30 years of sun exposure presented with a progressively enlarging red tumor on the dorsum of his left hand. A biopsy confirmed BD, and the tumor was excised with a 5 mm margin followed by skin grafting. Histopathological examination revealed subcutaneous MCC along with BD, with MCC cells forming small nests in the dermal papillary layer. Immunohistochemistry showed positive staining for synaptophysin and CK20 in a perinuclear dot pattern, confirming the MCC diagnosis. Given the patient's advanced age and the absence of positive surgical margins, a watch-and-wait approach was adopted. The patient has been under close outpatient monitoring, and no recurrence has been observed after six months. This case highlights the rarity of subcutaneous MCC coexisting with BD, with only a few reported cases of such coexistence. The unusual subcutaneous presentation and the presence of multiple micro-nodules instead of large atypical cell clusters suggest an early-stage MCC beneath BD. The pathogenesis of this coexistence remains unclear but raises important questions regarding the relationship between sun exposure and viral factors like Merkel cell polyomavirus (MCPyV), which was not tested in this case. The findings underscore the need for comprehensive diagnostic evaluation when encountering complex or atypical skin lesions. This report emphasizes the rarity of subcutaneous MCC coexisting with BD and underscores the importance of comprehensive diagnostic assessment in unusual cases. Further research is warranted to better understand the underlying mechanisms and to guide optimal management strategies for such rare and challenging presentations.Sep. 2024, Cureus, 16(9) (9), e69114, English, International magazineScientific journal
- A sebaceous carcinoma is rarely seen in extracutaneous sites. We present a 75-year-old man who was admitted with epigastralgia and melena. Endoscopic examination revealed an ulcer on the posterior wall of the gastric antrum, and distal gastrectomy was performed. Histopathological examination revealed thin to thick trabeculae of polygonal cells with scattered foci of foamy cells, whereas Sudan 3 staining showed lipid vacuoles. Immunohistochemistry was positive for both p40 and SALL4. After considering these findings, we suggest sebaceous differentiation as the diagnosis. To the best of our knowledge, this is the first case of gastric carcinoma with sebaceous differentiation.May 2023, ACG case reports journal, 10(5) (5), e01061, English, International magazineScientific journal
- Placental mesenchymal dysplasia (PMD) is a rare placental abnormality that is closely related to severe pregnancy complications. A 27-year-old woman with fetal growth restriction and placenta previa was referred to a university hospital at 22 gestational weeks (GW). She was suspected of having a twin pregnancy with a complete or partial hydatidiform mole and coexisting normal live fetus, because two separate placentas, an enlarged one with multiple cystic lesions and a normal one, were shown on ultrasound examinations. At 27 GW, she experienced a sudden intrauterine fetal death (IUFD) after bleeding due to placenta previa, despite confirmation of fetal well-being at 2 h before bleeding. After delivery, histopathological examination confirmed the diagnosis of PMD. This is the first documented case of a woman with PMD and placenta previa who had a sudden IUFD after bleeding. Patients with both PMD and placenta previa should be considered at extremely high risk for IUFD.Nov. 2021, The journal of obstetrics and gynaecology research, 47(11) (11), 4087 - 4092, English, International magazineScientific journal