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We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient’s condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography–computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8 + T cells. In addition, tumor cells were infected with Epstein–Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms.

Neuroblastoma is an embryonal malignancy of the sympathetic nervous system. Spontaneous regression and differentiation of neuroblastoma is observed in a subset of patients, and has been suggested to represent delayed activation of physiologic molecular programs of fetal neuroblasts. Homeobox genes constitute an important family of transcription factors, which play a fundamental role in morphogenesis and cell differentiation during embryogenesis. In this study, we demonstrate that expression of the majority of the human HOX class I homeobox genes is significantly associated with clinical covariates in neuroblastoma using microarray expression data of 649 primary tumors. Moreover, a HOX gene expression-based classifier predicted neuroblastoma patient outcome independently of age, stage and MYCN amplification status. Among all HOX genes, HOXC9 expression was most prominently associated with favorable prognostic markers. Most notably, elevated HOXC9 expression was significantly associated with spontaneous regression in infant neuroblastoma. Re-expression of HOXC9 in three neuroblastoma cell lines led to a significant reduction in cell viability, and abrogated tumor growth almost completely in neuroblastoma xenografts. Neuroblastoma growth arrest was related to the induction of programmed cell death, as indicated by an increase in the sub-G1 fraction and translocation of phosphatidylserine to the outer membrane. Programmed cell death was associated with the release of cytochrome c from the mitochondria into the cytosol and activation of the intrinsic cascade of caspases, indicating that HOXC9 re-expression triggers the intrinsic apoptotic pathway. Collectively, our results show a strong prognostic impact of HOX gene expression in neuroblastoma, and may point towards a role of Hox-C9 in neuroblastoma spontaneous regression.

Chordoma is a malignant bone tumor originating from notochordal remnants, most commonly occurring at the sacrococcygeal junction. We present a case of a 70-year-old male with chronic pain in the lower lumbar spine. MRI performed elsewhere revealed a large tumor that involved S4, S5, and the coccyx with a presacral soft tissue component. The lesion was heterogeneously hyperintense on T2-weighted images with a thick hypointense rim anteriorly. On T1-weighted images, the lesion showed a native hyperintense signal centrally probably due to hemorrhage. Based on this MRI, the diagnosis of chordoma was suggested. A spontaneous marked reduction in size was observed on a 4-week interval MRI performed at our institution before biopsy. Due to spontaneous tumor shrinkage along with peripheral enhancement, a differential diagnosis of infection or bleeding in a retrorectal cyst was proposed. This case teaches us that chordomas may contain a large hemorrhagic component, which is hyperintense on T1-weighted images and shows peripheral rim enhancement. Spontaneous shrinkage of a tumor may occur due to the resolution of a hematoma within weeks. Biopsy is key to obtain the correct diagnosis. Understanding the typical and more rare features of chordomas is key for MSK radiologists as well as pathologists. Chordomas are typically slow-growing tumors, but radiologists should be aware that intratumoral hemorrhage can lead to rapid changes in tumor size, which may be mistaken for either regression or progression of tumor. This case highlights the importance of considering hemorrhagic events within chordomas in the differential diagnosis when observing size fluctuations on imaging.

Introduction Pilocytic astrocytoma (PA) is the most common pediatric tumor, typically located in the cerebellum, with spontaneous regression observed mainly in patients with neurofibromatosis type 1 (NF1). However, spontaneous regression of PA without NF1 is rarely reported. Case Presentation Here, we describe a case of spontaneous regression of PA without NF1, located in the left frontal lobe with FGFR1-TACC1 fusion, in a 14-year-old boy who presented with epilepsy. Initial MRI revealed a lesion in the left middle frontal gyrus, and subsequent follow-up MRI demonstrated spontaneous regression. Despite this regression, the patient’s seizures persisted, leading to epileptic focus resection. Pathological examination confirmed PA with characteristic histological findings and FGFR1-TACC1 fusion. Conclusion This case suggests that FGFR1-TACC1 fusion may be linked to spontaneous regression of PA, even in the absence of NF1. Surgical intervention may remain necessary in cases of epilepsy associated with PA, regardless of tumor regression.

Background Neuroblastoma, the most common pediatric extracranial solid tumor, has heterogeneous clinical outcomes ranging from malignant progression to spontaneous regression. With the highest frequency of the elusive spontaneous regression, low-risk INSS Stage 4S neuroblastoma represents an ideal model for mechanistic investigation. Spontaneous regression is often accompanied by tumor differentiation, but the mechanisms underlying this process remain largely unclear. Methods Single-nucleus transcriptomics (snRNA-seq) data of neuroblastoma samples were obtained from the Synapse repository to investigate the composition of heterogeneous tumor cell clusters. The feature of the Stage 4S-specific tumor cell subpopulation was revealed through differential expression analysis, pathway enrichment analysis and pseudotime analysis, followed by clinical significance validation on public cohort datasets. The biological function of secreted SLIT3 was validated using multiple in vitro models, including recombinant protein treatment, conditioned medium treatment, and cell lines coculture, to confirm the intratumoral crosstalk effect. Orthotopic and subcutaneous xenograft models were established to verify SLIT3's in vivo function. Cellular bulk RNA-seq analysis was performed with or without SLIT3 recombinant protein treatment to discover the downstream pathways activated by SLIT3, followed by validation with specific pathway inhibitors. Results Analysis of snRNA-seq revealed a distinct subpopulation of tumor cells within INSS Stage 4S neuroblastoma, characterized by a spontaneous regression-like program progressing toward differentiation. Activated SLIT-ROBO signaling was found in the Stage 4S-specific tumor cell subpopulation, which strongly correlated with favorable prognosis. Further investigation into the secreted ligands in SLIT-ROBO related pathways revealed that SLIT3 displayed the most potent enrichment in Stage 4S tumors and the strongest differentiation-inducing effect. In vitro experiments using recombinant SLIT3 protein, conditioned medium, and cell lines coculture consistently demonstrated the capacity of SLIT3 to induce neuroblastoma cell differentiation via intratumoral crosstalk, as evidenced by increased neurite outgrowth and elevated expression of neuronal differentiation markers. Both orthotopic xenograft and subcutaneous xenograft models demonstrated that SLIT3 expression suppressed tumor growth, leading to in vivo tumor differentiation. Mechanistically, PLCβ/PKC signaling mediates the SLIT3-induced neuroblastoma cell differentiation. Conclusions Stage 4S-specific tumor cell subpopulation exhibits a spontaneous regression-like program, from which SLIT3 mediates intratumoral crosstalk and promotes neuroblastoma differentiation via PLCβ/PKC signaling. These findings provide new insights into the mechanism of spontaneous regression in neuroblastoma and offer novel therapeutic targets for differentiation-based treatment strategies.

The natural history of sporadic vestibular schwannoma is unpredictable, with tumors growing, non-growing and even showing spontaneous regression in some rare cases. This retrospective study aims to describe the radiologic signs characterizing and identifying the shrinking vestibular schwannoma. Involution was considered to have occurred if tumor size had decreased by 2 mm or more on its largest diameter. All magnetic resonance imaging scans were reviewed for tumor size, internal auditory meatus size, and tumor characteristics. Volumetric measurements were performed on the first and last scan. Audiometric data were collected at the first and last visit. Fourteen patients with a confirmed spontaneous regression were included, with a mean follow-up of 5 ± 2.6 years. The mean shrinkage rate was 0.9 ± 0.59 mm/year on 2D measurements, and 0.2 ± 0.17 cm3/year on volumetric measurements, with a relative shrinkage of 40 ± 16.9%. Two remarkable radiologic features were observed: First, a festooned aspect, defined by multiple curves in the tumor outline, noticed in 12 cases (86%); second, the appearance of cerebrospinal fluid filling the internal auditory meatus, associated with an enlargement of the internal auditory meatus compared to the contralateral side, and observed in 10 out of 13 cases with internal auditory meatus invasion (77%). Those two aspects were associated in 64% of cases. These two newly reported radiologic features could help neurosurgeons, oto-neurosurgeons and neuroradiologists to identify a spontaneous vestibular schwannoma involution at first visit. This could allow any treatment to be postponed, monitoring to be more widely spaced, and patients to be reassured.

A 90-year-old man underwent a colonoscopy due to abdominal distension, revealing half-circumferential Type 2 advanced cancers in the ascending and transverse colon. No distant metastasis was detected, and 3 months later, laparoscopic extended right hemicolectomy was performed for both lesions. Pathological examination revealed ulcers and mucus retention in the ascending colon lesion without tumor components. A small number of signet ring cell-like tumor cells were found in the regional lymph node of the ascending colon, while well-to-moderately differentiated tubular adenocarcinoma was observed on the serosal surface in the transverse colon. Tumor regression was observed in the ascending colon cancer and lymph-node metastasis. Mismatch repair (MMR) protein immunostaining was conducted on biopsy tissues from both lesions. The ascending colon lesion showed weak positivity for MLH1, positivity for MSH2 and MSH6, and negativity for PMS2, indicating MMR deficiency, whereas the transverse colon lesion showed positivity for all of them, indicating MMR-proficient tumor. This is the first case report of multiple advanced colon cancers, where only one lesion exhibited spontaneous regression after biopsy, suggesting a potential link between MMR deficiency and the spontaneous regression of colorectal cancer.

Purpose The purpose of this paper is to provide novel insight into the rare pediatric meningiomas. Methods We retrospectively analyzed pediatric surgical cases of meningioma during 2002 to 2017 in our institution. The preoperative, intraoperative, and the postoperative status were collected to find any unique features that has not reported in the past. Results Nine surgeries out of 5 patients were identified. The mean age was 7 years old (range 1–14 years old). Four patients were females. The mean tumor diameter was 52 mm (range 23–81 mm). The tumor locations were optic nerve sheath, Sylvian fissure, parasagittal, trigone of the lateral ventricle, and cerebellopontine angle. The Sylvian fissure meningioma without dural attachment (MWODA) was found in a 15-month-old female. A relapsed parasagittal meningioma showed regression in histological grade and residual tumor demonstrated spontaneous regression. In the initial surgeries, Simpson grade 1 resection was achieved in 2 cases. The pathological diagnoses were 1 meningothelial, 1 metaplastic, 2 atypical, and 1 clear cell meningiomas. The mean postoperative follow-up period was 71 months. Three patients experienced recurrence of the tumor. At the latest follow-up, all patients were free of radiological tumor recurrence or regrowth with a mean follow-up of 4 years (range 1–6.9 years). All patients were in the modified Rankin scale of 0–1. Conclusions MWODA is not considered to be rare in pediatric meningioma and should be included in the differential diagnosis. We presented a histologically regressed relapsed meningioma, which spontaneously regressed after subtotal resection. In the case of recurrent meningioma, surgical resection and adjuvant radiation therapy could be effective for long-term control of the tumor.

The exact mechanisms of spontaneous tumor remission or complete response to treatment are phenomena in oncology that are not completely understood. We use a concept from ecology, the Allee effect, to help explain tumor extinction in a model of tumor growth that incorporates feedback regulation of stem cell dynamics, which occurs in many tumor types where certain signaling molecules, such as Wnts, are upregulated. Due to feedback and the Allee effect, a tumor may become extinct spontaneously or after therapy even when the entire tumor has not been eradicated by the end of therapy. We quantify the Allee effect using an ‘Allee index’ that approximates the area of the basin of attraction for tumor extinction. We show that effectiveness of combination therapy in cancer treatment may occur due to the increased probability that the system will be in the Allee region after combination treatment versus monotherapy. We identify therapies that can attenuate stem cell self-renewal, alter the Allee region and increase its size. We also show that decreased response of tumor cells to growth inhibitors can reduce the size of the Allee region and increase stem cell densities, which may help to explain why this phenomenon is a hallmark of cancer.

Radiotherapy has been shown to potentially induce systemic anti-tumor immunity, a phenomenon that may be further enhanced by immune checkpoint inhibitor (ICI) therapy. However, whether this phenomenon occurs following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs) and its potential clinical implications remain poorly understood. We retrospectively analyzed 36 non-small-cell lung cancer (NSCLC) patients with multiple BMs treated with multi-session GKRS. Spontaneous tumor regression (STR) was defined as ≥ 30% volume reduction in non-irradiated tumors. Competing risks analysis and Cox regression were used to evaluate local progression, distant brain failure (DBF), and survival outcomes. In this study, 44% (16/36) of patients received ICI therapy. STR was observed in 38.9% (14/36) of the cohort. Comparative analysis revealed that patients received ICI therapy did not exhibited an improved overall survival (OS) ( p =  0.46), but demonstrated a trend toward a higher incidence of STR compared to those without ICI therapy (56.3% vs. 25.0%, p =  0.056). Multivariable regression analysis identified the absence of STR as an independent risk factor for mortality (Hazard Ratio [HR], 7.69; 95% CI: 1.61–33.33; p =  0.009) and local tumor progression (HR, 5.05; 95% CI: 1.71–14.93; p =  0.003). A systemic anti-tumor immunity could be induced by GKRS and cause STR of non-irradiated tumors. Patients exhibiting this phenomenon demonstrate significantly improved survival rates and local tumor control compared to those without this response. These findings underscore the potential immunomodulatory role of GKRS and its clinical implications in the management of BMs.