Infiltrative Growth Pattern Research Articles

The Immunopeptidomic Landscape of Ependymomas Provides Actionable Antigens for T Cell-Based Immunotherapy

Abstract Background Ependymoma are primary tumors of the nervous system. Due to their growth pattern, many ependymomas can be managed with neurosurgical resection alone. A substantial proportion of these tumors recurs or displays infiltrative growth patterns. Further established therapeutic options include radiation therapy. Systemic treatment options include platinum-based therapeutic regimes or a combination of lapatinib and temozolomide. Peptide-based immunotherapy represents a promising therapeutic strategy relying on the induction of tumor-specific T cells targeting human leukocyte antigens (HLA)-presented peptides. Our work aimed to analyze the landscape of naturally presented HLA class I and II ligands of primary ependymomas (EPN) to delineate EPN-associated antigens. Methods We investigated 22 EPN tissue samples using a comparative mass spectrometry-based immunopeptidomic approach. Additionally, EPN-specific antigens were functionally characterized in T cell-based immunogenicity assays. Results We discovered a subset of EPN-exclusive peptides including HLA-A*02 and HLA-A*25/HLA-A*26–restricted HLA ligands and identified a small panel of cancer/testis antigens (CTAs)-derived HLA ligands. Furthermore, we outlined immunopeptidomic alterations in different ependymoma subgroups and progressive ependymoma. Subsequently, we performed functional characterization of the previously identified HLA-A*02:01 restricted peptide FLDS to demonstrate immunogenicity in vitro. Conclusion The immunopeptidome landscape of EPNs provides actionable targets that could further be explored as a T-cell-based immunotherapeutic strategy in this tumor entity.

Cerebral Intricacies: Deciphering the Mystique of Primary Central Nervous System Angiosarcoma

AbstractAngiosarcoma of the central nervous system (CNS) is an exceptionally rare and aggressive vascular malignancy presenting significant diagnostic and therapeutic challenges. We report the case of a 22-year-old female with CNS angiosarcoma, highlighting diagnostic intricacies, therapeutic approaches, and management outcomes. Initial symptoms included headache and dizziness, with magnetic resonance imaging revealing a space-occupying lesion in the right parietal lobe, initially misinterpreted as cavernoma. Subsequent surgical resection confirmed angiosarcoma histologically, supported by immunohistochemical analysis showing endothelial markers. Treatment comprised local irradiation postoperatively, resulting in no recurrence or metastasis. Histopathological examination revealed an infiltrative growth pattern with atypical endothelial cells forming irregular vascular spaces. Challenges in diagnosis arise due to overlapping features with other intracranial lesions. Multimodal treatment approaches involving surgery, radiation, and chemotherapy were employed, although their efficacy remains uncertain. Prognosis remains poor, underscoring the imperative for collaborative efforts to enhance understanding and management of this rare malignancy. Our case contributes valuable insights to the limited literature on CNS angiosarcoma, emphasizing the need for comprehensive case studies to refine diagnostic and therapeutic strategies.

Incidentally Diagnosed Endolymphatic Sac Tumor on 68Ga-DOTA-TATE PET/CT in a Suspected Case of Pheochromocytoma.

Endolymphatic sac tumors (ELSTs) are rare, slow-growing, and locally aggressive neoplasms that originate from the epithelial lining of the endolymphatic duct and sac. These are characterized by their infiltrative growth pattern and the potential for local destruction of surrounding structures, including the inner ear and temporal bone. We report a case of an incidentally diagnosed sporadic ELST. The article provides an overview of the relevant literature on this topic and discusses the clinical, radiological, and surgical findings pertaining to this particular ELST case. Given their indolent growth pattern and lack of significant changes on interval imaging, surgical intervention is often deferred for these lesions.

Quantifying Tumor Budding: Implications for Prognosis in Gastric Adenocarcinoma.

The mechanism of tumor budding (TB) in gastric adenocarcinoma (GAC) and its relationship with biological indicators and prognostic significance, remains unclear. In this study, we conducted a comprehensive analysis using whole-slide imaging to evaluate TB in 75 cases of GAC. Our findings revealed the risk factors associated with TB in GAC and their impact on patient prognosis. The results indicate that the majority of cases exhibited a TB grade exceeding 10 (n=41), followed by 6-10 (n=15). Histologic grade (R=0.26, P=0.06), pT stage (R=0.56, P=0.00), neural invasion (R=0.29, P=0.01), marginal zone growth pattern (R=0.25, P=0.02), and basal zone growth pattern (R=0.38, P=0.001) are associated with TB in GAC. Logistic regression analysis revealed that the infiltrative growth pattern in both the marginal zone (odds ratio=5.90, 95% CI: 1.04-33.44, P=0.05) and basal zone (odds ratio=12.80, 95% CI: 2.03-80.68, P=0.01) were identified as risk factors for TB in GAC. Univariate analysis demonstrated a negative correlation between TB and TB grade with overall survival and progression-free survival in GAC patients. Furthermore, the multivariate COX analysis revealed that TB and TB grade, along with American Joint Committee on Cancer stage, lymph node metastasis, and pT stage, independently influenced the prognosis of GAC patients. In conclusion, a comprehensive evaluation of TB could serve as a significant histologic marker for risk stratification in GAC.

Invasive Lobular Carcinoma in the Screening Setting.

Invasive lobular carcinoma (ILC) is the second-most common histologic subtype of breast cancer, constituting 5% to 15% of all breast cancers. It is characterized by an infiltrating growth pattern that may decrease detectability on mammography and US. The use of digital breast tomosynthesis (DBT) improves conspicuity of ILC, and sensitivity is 80% to 88% for ILC. Sensitivity of mammography is lower in dense breasts, and breast tomosynthesis has better sensitivity for ILC in dense breasts compared with digital mammography (DM). Screening US identifies additional ILCs even after DBT, with a supplemental cancer detection rate of 0 to 1.2 ILC per 1000 examinations. Thirteen percent of incremental cancers found by screening US are ILCs. Breast MRI has a sensitivity of 93% for ILC. Abbreviated breast MRI also has high sensitivity but may be limited due to delayed enhancement in ILC. Contrast-enhanced mammography has improved sensitivity for ILC compared with DM, with higher specificity than breast MRI. In summary, supplemental screening modalities increase detection of ILC, with MRI demonstrating the highest sensitivity.

UDA-GS: A cross-center multimodal unsupervised domain adaptation framework for Glioma segmentation

Gliomas are the most common and malignant form of primary brain tumors. Accurate segmentation and measurement from MRI are crucial for diagnosis and treatment. Due to the infiltrative growth pattern of gliomas, their labeling is very difficult. In turn, the already available annotated datasets, such as well-known BraTS, are difficult to generalize to multicenter unannotated datasets due to the variations in imaging machines and parameters. To address this challenge, a novel unsupervised domain adaptation framework for glioma segmentation (UDA-GS) is proposed. UDA-GS uses GliomaMix to mix labeled tumors with unlabeled images and aligns the features of the same tumor, allowing the network to adapt to different backgrounds across different centers. Additionally, the framework leverages tumor information generated by GliomaMix as prior knowledge for self-supervised regression tasks to enhance feature encoding for tumors in different domains. Using Mean-Teacher as the basic framework, UDA-GS also incorporates weighted consistency regularization and mask combining strategy to achieve efficient unsupervised domain adaptation. Quantitative and qualitative evaluations were conducted on 1179 cases across 27 centers, without requiring any local annotations. The results demonstrate that UDA-GS outperforms the second-best method in terms of Dice coefficient segmentation metrics by 18.2 %, 6.9 %, and 4.6 % for the whole tumor, tumor core, and enhanced tumor, respectively, on the internal testing set. Additionally, the evaluations reveal that doctors express greater satisfaction with the segmentation outcomes achieved by UDA-GS in comparison to other methods including the segment anything model (SAM).

Comprehensive pathological evaluation of risk factors for metastasis after endoscopic resection of superficial esophageal squamous cell carcinoma.

Esophageal cancer is a major cause of cancer mortality worldwide. Endoscopic resection (ER) is a curative treatment for esophageal squamous cell carcinoma (ESCC). Predicting risk of metastasis is crucial for post-ER management. In this study, we aimed to identify predictors of metastasis by examining endoscopically resected specimens. The cohort of this retrospective multicenter study comprised 422 patients who had undergone ER for ESCC from 1994 to 2017. Inclusion required a histological diagnosis of pT1a-muscularis mucosa or pT1b-submucosa (SM) cancer. Central pathological review comprehensively evaluated depth of invasion, lymphovascular invasion (LVI), droplet infiltration (DI), infiltrative growth pattern, histological differentiation, intraductal and intraglandular involvement, solitary nest, resected margin, and other factors. Logistic regression was used to identify predictors of metastasis. Metastases were identified in 103 patients. Univariate analysis identified LVI, depth of invasion, and DI as significant predictive factors. Multivariate analysis identified LVI, depth of invasion pT1b-SM2 (odds ratio 2.72) and indeterminate (positive vertical margin) (odds ratio 3.63) compared with the reference category of pT1b-SM1 as independent predictors of metastasis. Conversely, there were no significant associations between metastasis and lesion size, differentiation, cytological atypia, or infiltration pattern. Subgroup analysis showed that both the number and layer of LVI were associated with metastasis risk. In addition, four or more foci of DI was an independent predictor of LVI. LVI and depth of invasion were significant predictors of metastasis in ESCC. Detailed pathological evaluation and standardized criteria are essential for accurately assessing risk of metastasis and guiding post-ER treatment strategies.

SURG-37. ADVANCING GLIOBLASTOMA RESEARCH THROUGH RESECTION MODELS

Abstract Regardless of its cellular and molecular heterogeneity, glioblastoma (GBM) tumors share a common hallmark: an infiltrative growth pattern that poses challenges to surgical resection and leads to incomplete tumor removal. As part of the current standard-of care treatment, patients undergo surgery in addition to temozolomide and radiation therapy. In GBM research, mice are often used to replicate tumor development and test treatments, but this approach typically omits the crucial aspects of surgical intervention, and thus fails to recapitulate important aspects of human GBM disease progression at the surgical margin. Here we address this challenge by developing a technique for tumor resection in mice. First, we implant the infiltrative patient derived GBM cell line Akaluc G16302 in the frontal cortex, specifically at anteroposterior 2mm, mediolateral 0.5mm, dorsoventral 1mm starting from bregma. After 6 weeks, we anesthetize the mouse and do a craniotomy at the injection site, approximately 3-4mm in diameter. We perform a circumferential cut using a curved Fukushima scissor at the edges of the craniotomy area and scoop the tumor core, mimicking surgical resection. Mice survive the surgery and are alive up to 37 days post-resection. Histology confirms resection of tumor cells and a surgical tumor margin remaining in the xenograft animal. In our pilot study, mice undergoing resection displayed significantly increased overall survival compared to mice without surgery (log-rank p-value = 0.0448; n=6; survival range of 91-100 days for control and 97-107 days for resected mice), recapitulating survival benefit also seen in humans. This preliminary data demonstrates the feasibility of the technique and resection-associated survival benefit. Such advancements enable researchers to more accurately replicate the biology of GBM progression and treatment response observed in human patients, bringing us closer to modeling the clinical scenario in mice. Key words: Glioblastoma, resection, biopsy

A rare clinical manifestation of plexiform neurofibroma in the absence of neurofibromatosis-1: a case report

Plexiform neurofibroma is a benign tumor of peripheral nerves that occurs in up to 30% of patients with neurofibromatosis type-1 (NF-1). We present a case of a 15-year-old male patient without NF-1, with an 11-year history of a slow growing, painless mass on the left side of the back extending to the gluteal region, with no constitutional symptoms but with some scoliosis. Histology of the mass was compatible with a plexiform neurofibroma. Plexiform neurofibromas commonly occur in, but are not limited to the craniofacial region. The mainstay of treatment is surgical resection, but complete resectability is challenging due to their locally infiltrative growth pattern. This highlights the need for patient-specific management strategies, even when established guidelines are in place.

Metastatic glioblastoma multiforme on skin and subcutaneous tissue

Glioblastoma multiforme (GBM) is characterized by its infiltrative growth pattern and high recurrence rate despite treatment. While local progression within the central nervous system (CNS) is the rule, manifestations outside the CNS, particularly skin and subcutaneous metastases, are very infrequent and seldom reported in the literature. The authors reviewed the current understanding of this rare condition, with the main purpose of giving visibility to its clinical presentation and prognostic implications, thus improving clinical management and encouraging research in this area. A PubMed, Cochrane Library, and EMBASE search from database inception through March 2024 was conducted. In this way, we compiled a total of thirty-five cases in our review. As far as we know, our work gathers the largest number of patients with this condition. Remarkably, we observed that the typical presentation of soft-tissue high-grade glioma metastases is the finding of subcutaneous erythematous nodules in patients previously operated on for a primary CNS tumor, within the craniotomy site and nearby, mostly in the first year after the initial surgery. It was also noted that there is a trend of developing a concomitant CNS recurrence and/or other metastases in different locations, either simultaneously or subsequently. From here, we propose some possible mechanisms that explain the extracranial spread of GBM. We concluded that a poor outcome is expected from the diagnosis of skin and subcutaneous metastases: the mean overall survival was 4.38 months. Yet, assessing individual characteristics is always mandatory; a palliative approach seems to be the best option for the majority of cases.

Sneaky DCIS-looking Invasive Ductal Carcinoma of the Breast in the Extensive DCIS Background

Abstract Introduction/Objective In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much more easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Methods/Case Report Retrospective analysis of the histologic and immunohistochemical findings of pure DCIS and DCIS-looking invasive ductal carcinoma. Results (if a Case Study enter NA) Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas. Immunohistochemical (IHC) staining showed that myoepithelial markers, p63 and smooth muscle myosin heavy chain (SMMHC), were retained at the periphery of all the expanded acini in one area. Unexpectedly and surprisingly, p63 and SMMHC were completely lost at the periphery of part of the DCIS-looking acini in another area, immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Conclusion Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize sneaky DCIS-looking invasive ductal carcinoma in the extensive DCIS background. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Clinicopathological and molecular characteristics of microsecretory adenocarcinoma in salivary gland

Objective: To investigate the clinicopathological, immunohistochemical, and molecular genetic characteristics of microsecretory adenocarcinoma (MSA) of the salivary gland, and to improve the understanding of this rare tumor. Methods: Cases originally diagnosed as MSA at the Department of Oral Pathology, the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine were retrospectively collected. The cases of polymorphous adenocarcinoma and adenocarcinoma, not otherwise specified from January 2000 to January 2020 were reviewed to identify potential misdiagnosed MSA cases. Clinicopathological analysis and follow-up of all confirmed MSA cases were performed, and relevant literature was reviewed. Results: A total of 4 MSA cases were identified, including 2 screened from the polymorphous adenocarcinoma cohort. Of the 4 MSA patients, 3 were male and 1 was female, with an average age of 53 years (range, 37-67 years). Three cases occurred in the palate, and one in the buccal region. The clinical manifestation was usually a slow-growing painless mass. Tumors were generally small, with a maximum diameter ranging from 0.7 to 1.8 cm (average, 1.2 cm). Microscopically, the tumor was unencapsulated and showed an infiltrative growth pattern. The tumor cells appeared small in size and showed bland, cubic and flattened cytological features, forming microcystic lumens and glandular tubes. Significant basophilic secretions were seen in the lumens. Between the tumor nests there was fibro-myxoid stroma. Immunohistochemistry showed diffusely or partially positive staining for cytokeratin 7, S-100, SOX-10, p63 and vimentin and negative staining for p40, mammaglobin, and calponin. The proliferation index of Ki-67 was relatively low (1%-3%). Four MSA cases all harbored SS18 gene rearrangement as shown by fluorescence in situ hybridization (FISH), including 2 cases with MEF2C::SS18 fusion gene through RNA-targeted next generation sequencing. All 4 patients underwent surgical resection without any adjuvant treatments. Three patients were followed up for a period of 2 to 203 months. No tumor recurrence, metastasis, or disease-related death was found. Conclusions: Salivary gland MSA is a novel and rare low-grade carcinoma with unique and consistent histological morphology, immunophenotype, and molecular changes. Immunohistochemical staining and SS18 break apart FISH are useful for the diagnosis of the tumor with atypical morphology and high-grade transformation.

N-Acetyl-L-Cysteine (NAC) Blunts Axitinib-Related Adverse Effects in Preclinical Models of Glioblastoma.

Axitinib is a tyrosine kinase inhibitor characterized by a strong affinity for Vascular Endothelial Growth Factor Receptors (VEGFRs). It was approved in 2012 by Food and Drug Administration and European Medicines Agency as a second line treatment for advanced renal cell carcinoma and is currently under evaluation in clinical trial for the treatment of other cancers. Glioblastoma IDH-wild type (GBM) is a highly malignant brain tumor characterized by diffusely infiltrative growth pattern and by a prominent neo-angiogenesis. In GBM, axitinib has demonstrated a limited effectiveness as a monotherapy, while it was recently shown to significantly improve its efficacy in combination treatments. In preclinical models, axitinib has been reported to trigger cellular senescence both in tumor as well as in normal cells, through a mechanism involving intracellular reactive oxygen species (ROS) accumulation and activation of Ataxia Telangiectasia Mutated kinase (ATM). Limiting axitinib-dependent ROS increase by antioxidants prevents senescence specifically in normal cells, without affecting tumor cells. We used brain tumor xenografts obtained by engrafting Glioma Stem Cells (GSCs) into the brain of immunocompromised mice, to investigate the hypothesis that the antioxidant molecule N-Acetyl-L-Cysteine (NAC) might be used to reduce senescence-associated adverse effects of axitinib treatment without altering its anti-tumor activity. We demonstrate that the use of the antioxidant molecule N-Acetyl-Cysteine (NAC) in combination with axitinib stabilizes tumor microvessels in GBM tumor orthotopic xenografts, eventually resulting in vessel normalization, and protects liver vasculature from axitinib-dependent toxicity. Overall, we found that NAC co-treatment allows vessel normalization in brain tumor vessels and exerts a protective effect on liver vasculature, therefore minimizing axitinib-dependent toxicity.

A Rapidly Growing Nodule on the Eyebrow of a Pediatric Patient

A 11-year-old Caucasian girl presented to our Dermatology Unit with a 2-month history of an erythematous nodule, localized to the medial portion of her left eyebrow, rapidly growing in the two weeks before presentation. The histopathological examination revealed a dermal multi-nodular epithelial neoplasm composed of clear cells, squamous cells, and glandular cells, characterized by cytologic atypia, high mitotic activity, and an infiltrative deep growth pattern. The immunohistochemical profile of the lesion was as follows: CKAE1/AE3+, EMA+, CK8/18+, CK7+, CK19+, AR negative, p63 focally +, Ki67 25%, rare cells GCDFP15+, p53+.

The prognostic significance of growth pattern, tumor budding, poorly differentiated clusters, desmoplastic reaction pattern and tumor-stroma ratio in colorectal cancer and an evaluation of their relationship with KRAS, NRAS, BRAF mutations

Growth pattern (GP), tumor budding (TB), poorly differentiated clusters (PDC), desmoplastic reaction pattern (DRP) and tumor-stroma ratio (TSR) are prognostic histomorphological parameters in colorectal cancer (CRC). Correlations between these parameters, their individual prognostic values, and their relationship with KRAS/NRAS/BRAF mutations have not been comprehensively examined. We aimed to investigate these associations, which have not been previously explored in this combination. 126 CRC cases were included. GP, TB, PDC, DRP and TSR were evaluated by two experienced pathologists. KRAS/NRAS/BRAF mutation profile were determined using qPCR. Demographic, clinicopathological and survival data were recorded. Interrelations were investigated by statistical analysis. Infiltrative GP was more frequent in high-score TB, PDC-G3, and stroma-high tumors (p < 0.05). High-score TB was more common in PDC-G3 and stroma-high tumors (p < 0.05). Immature DRP was more frequent in stroma-high tumors (p = 0.014). Among histomorphological parameters, a significant relationship was found only between infiltrative GP and the presence of KRAS mutation (p = 0.023). Moreover, GP was significantly associated with pT, lymphatic invasion, perineural invasion (p < 0.05). Effects on survival were assessed using Kaplan-Meier method and Cox proportional hazards model. TB and PDC were identified as independent predictors of overall survival. Higher TB score (p = 0.008) and higher PDC grade (p = 0.013) lead to worse survival. Interestingly, GP, DRP, TSR or KRAS/NRAS/BRAF mutations were not associated with overall survival. Our results highlight the prognostic significance of TB and PDC. We suggest incorporating TB and PDC into routine CRC reports. The association of KRAS mutation with infiltrative GP supports its role in the acquisition of invasive behavior.

247. INVESTIGATION ON THE RECURRENCE AND PROGNOSIS WITH MM/SM1 OESOPHAGEAL SUPERFICIAL CANCER AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION

Abstract Background The therapeutic strategy for MM/SM1 oesophageal superficial cancer (OSC) after endoscopic submucosal dissection (ESD) still remains controversial, but there are some opinions that cut-end positive, vascular invasion positive, infiltrative growth pattern (INF) c, and poorly differentiated carcinoma are the risk factors for the recurrence of lymph-node (LN) or distal metastases. Methods This study aimed to investigate the recurrence and prognosis after ESD in patients with MM/SM1 OSC who do not have the risk factors. We performed ESD in 167 patients with OSC, and among these, we enrolled 15 patients with MM/SM1 OSC who did not have cut-end positive, vascular invasion positive, INF c, or poorly differentiated carcinoma in this study. The clinical background characteristics, endoscopic findings, additional therapy after ESD, recurrence, and prognosis of these patients were investigated. Results The median age of the patients, including 11 males and 4 females, was 69 years (range: 59–84). The mean follow-up duration was 75 months (range: 17-137). Of these, 3 patients had chronic obstructive pulmonary disease, 1 had cerebrovascular disease, and 1 had chronic heart failure. Regarding the lesion location, 2 patients had the lesion at Ut, 11 had at Mt, and 2 had at Lt. In 3 patients, the lesion occupied more than 3/4 of the lumen. We found 2 patients with elevated-type lesions, 10 with flat-type lesions, and 3 with depressed-type lesions. The mean long diameter of the lesions was 29 mm (range: 11-47). Regarding the lesion depth, there were 12 lesions in MM and 3 lesions in SM1. A total of 4 patients received additional radiation therapy, and the remaining 11 patients were followed up without additional therapy. The patients who received additional therapy did not have recurrences; however, 4 among the 11 patients without additional therapy manifested LN and lung metastases. Furthermore, 3 patients died because of the progression of oesophageal cancer, and another patient received chemotherapy. Conclusion In this study we showed that follow-up without additional therapy after ESD in patients with MM/SM1 OSC is unlikely to be acceptable despite not having risk factors. Therefore, we should urgently develop a treatment strategy for patients with MM/SM1 OSC after ESD.

Tumor budding and complete epithelial mesenchymal transition correlate with late nodal metastasis in early-stage tongue squamous cell carcinoma

BackgroundLate nodal metastasis is a poor prognostic factor for early-stage tongue squamous cell carcinoma. However, for most early-stage patients, there is a low risk for late nodal metastasis, which currently lacks a diagnostic marker. Tumor budding is a nodal metastasis risk factor in other human cancers. Here, we evaluated tumor budding by partial or complete epithelial-mesenchymal transition and Ovol2 expression, a transcription factor that directly suppresses epithelial-mesenchymal transition. MethodsSixty-six T1–2N0 patients were enrolled in this retrospective study. Tumor expressions of E-cadherin and vimentin (epithelial-mesenchymal transition markers) and Ovol2 were assessed by immunohistochemistry. Tumor histopathological and immunohistochemical features, mode of invasion, and tumor budding were assessed. Correlations between these potential predictive factors and late nodal metastasis were determined statistically. ResultsUnivariate analysis demonstrated lymphoid infiltrate, perineural invasion, infiltrative growth pattern, tumor budding, vimentin positive, and complete epithelial-mesenchymal transition were significant factors of late nodal metastasis (all P < 0.05), observed in 25.8 % of patients. Multivariate analysis identified tumor budding and vimentin positive were independent prognostic factors (both P < 0.025). Ovol2 expression was significantly decreased in partial and complete epithelial-mesenchymal transition cells (both P < 0.01) compared with normal epithelia. Univariate analysis, but not multivariate analysis, showed Ovol2 correlated with depth of invasion and tumor budding (both P < 0.05). ConclusionTumor budding and vimentin expression are risk factors for late nodal metastasis in T1–2N0 tongue squamous cell carcinoma. Ovol2 might be involved in the early stages of epithelial-mesenchymal transition. Evaluation of these factors might identify patients susceptible to late nodal metastasis who require elective neck dissection.

Notochordal cell derived lesions: a 55-year casuistic analysis of 50 cases with radiologic-pathologic correlation in a tertiary referral hospital, and literature review.

Distinct lesions are derived from notochordal cells (NCDL), ranging from benign to malignant ones. This study presents fifty NCDL cases diagnosed in a tertiary hospital of reference from the past 55 years: forty-two conventional chordomas, including one chondroid chordoma subtype, four benign notochordal cell tumors (BNCT), two conventional chordomas with BNCT foci, and two dedifferentiated chordomas. All patients were adults. Three BNCT were incidentally diagnosed, and one case presented local pain. Chordomas began with local pain and/or neurological symptoms. BNCT were well-defined intraosseous lesions, hypointense on T1-weighted images (WI) and hyperintense on T2-WI, without enhancement in the contrast. Conventional chordomas, including its chondroid subtype, were lobulated masses with cortical disruption and soft tissue extension, hypointense on T1-WI and hyperintense on T2-WI, with variable contrast enhancement. BNCT were histologically composed of solid sheets of vacuolated cells with clear cytoplasm and round and central nuclei. No atypia, lobular growth pattern, myxoid matrix, or bone infiltration were seen. Conventional chordomas were histologically composed of physaliphorous cells in a myxoid stroma with lobulated and infiltrating growth patterns. Observational follow-up using radiological controls was decided on for the BNCT cases. None of these cases presented local recurrence or metastasis. En-bloc resection and adjuvant radiotherapy were selected for sacral and vertebral chordoma cases. Sixteen patients died due to tumor-related factors; twenty-eight presented local recurrence, and four developed distant metastases. New therapeutic options are being studied for chordoma cases. Clinical, radiological, and histopathological data are necessary to properly diagnose and follow up of NCDL.

Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N=23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Carcinoma Cuniculatum Masquerading as Eumycetoma: An Unacquainted Entity Posing a Diagnostic Dilemma.

Carcinoma cuniculatum (CC) is a rare and distinct clinicopathological variant of well-differentiated squamous cell carcinoma. It is a rare and slow-growing tumor with a peculiar infiltrative growth pattern resembling rabbit burrows (cuniculi). It usually occurs over the plantar aspect of the foot but can also occur at other sites like the oral cavity and genitals. The pathogenesis is unknown, with various hypotheses of trauma as proposed by different authors. It is essential to be aware of this entity as it commonly mimics benign and other low-grade squamous cell carcinoma (SCC). Diagnosis of CC can be challenging and requires repeated histological evaluation and clinical correlation. Herein, we present a case report of CC of the plantar and dorsal aspect of the foot in a 60-year-old male with a history of multiple chronic non-healing ulcers, which was clinically suspected as eumycetoma and remained inconclusive on numerous biopsies.