Malignant transformation of nevus sebaceous to basal-cell carcinoma: Case series, literature review, and management algorithm.

Nevus sebaceous (NS) is a common congenital hamartoma of the skin composed predominantly of sebaceous glands. Although most NS are benign skin tumors, malignant transformations have been reported. There is still controversy about the lifetime risk of malignant degeneration and precise surgical criteria. This study reports cases of malignant degeneration and suggests a surgical treatment algorithm. The medical records of patients with basal-cell carcinoma (BCC) arising from NS between January 2001 and January 2021 were retrospectively reviewed. Patient demographics including lesion location, and tumor size were investigated. The symptoms, histological findings before and after excision, complications, and recurrence during 2-year follow-up periods were investigated. Ten patients were identified with BCC arising from NS lesions. All patients were female and the mean age was 52.11 years. All patients complained of sudden morphological changes, the most common type being rapid color changes. Two cases had histological findings that showed a miss-match between punch biopsy and excisional biopsy results. No recurrence was detected 2 years after surgeries in any patients. Cases after third stage, especially in over 40 years who report morphologic changes, should undergo total surgical excision as the first approach, with strong suspicion of malignant degeneration.

Metabolic profiling of human gliomas assessed with NMR.

Little is known about the underlying metabolic alterations of gliomas. The objective of this study was to analyze metabolomic profiles of gliomas diagnosed according to revised WHO classification to demonstrate metabolic signatures beyond isocitrate dehydrogenase (IDH) 1/2 mutation. 1H NMR spectroscopy of tumor extracts was performed to analyze brain tumor metabolism. We detected 46 metabolites including 2-hydroxyglutarate from human brain tumors. Metabolic profiles obtained were analyzed using multivariate analysis and MetaboAnalyst 3.0, a pathway analysis tool. We found that lactate, glutamate, alanine, glutamine, 2-hydroxglutarate, serine, O-phosphocholine, glycine, glycerol, myo-inositol, aspartate, leucine, threonine, creatine, and valine had top-ranked VIP scores in metabolic pathway analyses of glioma. Major metabolism pathways perturbed in glioma included alanine/aspartate/glutamate metabolism, glycine/serine/threonine metabolism, pyruvate metabolism, taurine/hypotaurine metabolism, and d-glutamine/d-glutamate metabolism. Altered metabolites were defined between low-grade and high-grade gliomas. We identified metabolomics signatures of gliomas associated with 2-hydroxglutarate and glioma grade. Metabolic approach may lead to metabolomic cluster-precision strategy and development of metabolic anti-glioma therapy in the future.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer.

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II-IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I-positive tumors than in HLA-I-negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Prognostic value of systemic inflammatory markers and development of a nomogram in breast cancer.

Systemic inflammatory markers derived from peripheral blood cell, such as the neutrophil-lymphocyte ratio (NLR), derived neutrophil-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), have been demonstrated as prognostic markers in several types of malignancy. Here, we investigated and compared the association between systemic inflammatory markers and survival and developed a prognostic nomogram in breast cancer patients. We reviewed the clinical and pathological records of 661 patients diagnosed with invasive breast carcinoma between 1993 and 2011. The NLR, dNLR, PLR and LMR in the immediate preoperative period were assessed. We analyzed the relationship between these inflammatory markers and clinicopathologic variables, disease-specific survival (DSS), and disease-free survival (DFS) in patients. A nomogram was developed to predict 3- and 5-year DSS for breast cancer. In the univariate analysis, high NLR, dNLR, PLR and low LMR were all significantly associated with poor DSS and DFS. In the multivariate analysis, only the PLR (HR 3.226, 95% CI 1.768-5.885 for DSS and HR 1.824, 95% CI 1.824-6.321 for DFS) was still identified as an independent predictor of outcomes. A subgroup analysis revealed that the PLR was the sole independent marker predicting poor DSS in patients with lymph node metastasis (HR 2.294, 95% CI 1.102-4.777) and with luminal subtype (HR 4.039, 95% CI 1.905-8.562). The proposed nomogram, which includes the PLR, shows good accuracy in predicting DSS with a concordance index of 0.82. PLR is an indicator of systemic inflammation as a part of the host immune response. As an independent prognostic factor, an elevated preoperative PLR is superior to the NLR, dNLR, and LMR in predicting clinical outcomes in patients with breast cancer. Moreover, the nomogram incorporating the PLR could accurately predict individualized survival probability in breast cancer.

Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts.

BACKGROUND: Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. PATIENTS AND METHODS: We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. RESULTS: A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. CONCLUSION: Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery.

Hemangioma of the Maxillary Sinus Presenting as a Mass: CT and MR Features.

Hemangiomas of the sinonasal tract are rare, and because these lesions lack the typical signs or symptoms, they can be confused with other malignant conditions. We report a case of cavernous hemangioma of the maxillary sinus in a 68-year-old man that was completely resected by endoscopic sinus surgery. Although computed tomography (CT) and magnetic resonance imaging (MRI) showed several enhancing areas within the tumor, the substantial bone erosion and remodeling made it difficult to differentiate this cavernous hemangioma from other expansile maxillary sinus lesions. We present the CT and MR findings of this lesion and discuss the differential diagnoses and potential therapeutic approaches.

A possible complementary tool for diagnosing tuberculosis: a feasibility test of immunohistochemical markers.

Differentiation of tuberculous granuloma (TG) from non-tuberculous granuloma (NG) is histopathologically difficult. We evaluated the usefulness of selected immunohistochemical markers to differentiate tuberculous granuloma (TG) and non-tuberculous granuloma (NG). We selected six biomarkers (FoxP3, TNF-beta, E-selectin [ESEL], indoleamine 2,3-dioxygenase [IDO], lactoferrin [LACT], and tartrate-resistant acid phosphatase [TRAP]) and immunohistochemically analyzed their expression in the presence of two types of granulomatous tissue samples, TG (n = 36) and NG (n = 31), using a microarray format. Three of those six biomarkers (LACT, IDO, and TNF-beta) were moderately accurate in discriminating TG from NG, individually and in combination, according to ROC analysis (AUC = 0.7-0.89, sensitivity = 55.6-77.8%, specificity = 71.0-100%). Our data indicate that selected immunohistochemical markers (LACT, IDO, and TNF-beta) can be used in ancillary tests to differentiate TG from NG in tissue samples. Further large-scale studies are required to validate our results.

NRP-1 expression is strongly associated with the progression of pituitary adenomas.

The purpose of the present study was to identify a predictive marker associated with tumor progression or recurrence. We investigated the expression of p53, Ki-67, Bax, Bcl-2, vascular endothelial growth factor (VEGF)-A, VEGFR-1, VEGFR-2 and neuropilin-1 (NRP-1) in pituitary adenomas (PAs) with/without tumor progression during follow-up periods. We compared the expression of these molecules in primary and recurrent specimens to identify a predictive marker associated with tumor progression. Nineteen patients had no progression for more than 5-years of follow-up. Nine patients had tumor progression within 5 years of their first transsphenoidal surgery (TSS) surgery and underwent re-TSS for treating progression of adenoma. Tumor size was larger and involvement of the cavernous sinus was more frequent in the progression group than these variables in the no progression group. A strong association was observed between NRP-1 expression and tumor progression. No significant risk for developing tumor progression was associated with Ki-67, p53, Bax, Bcl-2, VEGFR-1, VEGFR-2, or VEGF-A expression. Four of nine patients showed strong NRP-1 immunoreactivity in progression specimens. Negative NRP-1 immunoreactivity in the initial specimens was converted into strong positivity in the progression specimens of five patients. NRP-1 could be a relevant PA marker of progression and could be a potential target for medical therapy.

Immunohistochemical Expression of DCUN1D1 in Non-small Cell Lung Carcinoma: Its Relation to Brain Metastasis.

PURPOSE: Non-small cell lung carcinoma (NSCLC) comprises 75-85% of all lung cancers, and approximately 25% of all NSCLC patients develop brain metastasis. There are no reliable markers for predicting in which patients this metastasis will occur. DCUN1D1, also known as squamous cell carcinoma-related oncogene, is associated with tumor progression and poor outcomes in NSCLC. The objective of this study was to investigate the role of DCUN1D1 expression in cases of brain metastasis due to NSCLC. MATERIALS AND METHODS: Primary tumor samples from a total of 71 cases of NSCLC, either with (n=40) or without (n=31) brain metastasis, were evaluated for DCUN1D1 expression by immunohistochemistry analysis. RESULTS: DCUN1D1 expression was detected in 16 patients (23%) and tended to correlate with T classification (15% of T1-2 tumors vs. 30% of T3-4 tumors, p=0.083). DCUN1D1 expression was significantly associated with tumor stage. It was observed in none of the patients with stage I disease, 10% of those with stage II disease, and 29% with stage III disease (p=0.009). In addition, 14 of 16 DCUN1D1-positive patients resulted in brain metastasis (p=0.01). The odds ratio of brain metastasis for patients with DCUN1D1 expression was 3.112 (p=0.009). CONCLUSION: DCUN1D1 expression may play a role in tumor progression and development of brain metastasis in patients with NSCLC. Evaluation of DCUN1D1 expression may provide assistance in identifying those patients who are at higher risk for brain metastasis.