A 51-Year-Old Woman with Advanced Peritoneal Mesothelioma and Stage 3b Chronic Kidney Disease Treated with Cytoreductive Surgery and Bidirectional Intraperitoneal Cisplatin and Ifosfamide Chemotherapy: A Case Report.

BACKGROUND Malignant mesotheliomas are rare, yet highly malignant tumors. Mesotheliomas are tumors that develop from mesothelial surfaces, with the pleura being the most common, followed by the peritoneum. The diagnosis of malignant peritoneal mesothelioma (MPM) is usually established when the disease is advanced, owing to the nonspecific clinical appearance and abdominal symptoms. Initially, MPM was treated with palliative systemic chemotherapy, with or without palliative surgery. However, cytoreductive surgery (CRS) combined with bidirectional intraoperative chemotherapy (BDIC) has recently emerged as a treatment option for MPM. BDIC creates a bidirectional chemotherapy gradient in the peritoneal tumor cells through the simultaneous use of intraperitoneal and intravenous chemotherapy. CRS, combined with BDIC (CRS-BDIC), allows the complete elimination of residual tiny tumor cells after complete removal of the visible tumor nodules. CASE REPORT Herein, we present a case of a 51-year-old woman with MPM and chronic kidney disease (CKD) stage 3b. Her treatment consisted of neoadjuvant chemotherapy and immunotherapy, followed by CRS-BDIC using intraperitoneal cisplatin and doxorubicin, and intravenous ifosfamide. The surgery was successful, with no immediate complications or decline in the patient's kidney function. On follow up 2 months later, the patient denies suffering any chemotherapy-related adverse effects, and her kidney profile remains stable. CONCLUSIONS In conclusion, nephrotoxicity, a known adverse effect of cisplatin and ifosfamide, might not be a contraindication for the use of these potentially nephrotoxic drugs in CRS-BDIC in patients with renal impairment.

Comprehensive Transcriptome Analysis Reveals the Distinct Gene Expression Patterns of Tumor Microenvironment in HPV-Associated and HPV-Non Associated Tonsillar Squamous Cell Carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy.

Intraoral angiosarcoma with unusual clinical presentation: A case report.

Introduction: Angiosarcoma is a rare and highly aggressive soft tissue malignancy originating from vascular and lymphatic endothelial cells. Epithelioid angiosarcoma is the rarest subtype of angiosarcoma, characterized by the proliferation of large polygonal cells with an epithelioid feature. The occurrence of these tumors in the oral cavity is highly uncommon, and immunohistochemistry staining is essential to differentiate epithelioid angiosarcoma from mimicking lesions. Aim: To present a case of intraoral angiosarcoma with an unusual clinical presentation and behavior and to report, to the best of our knowledge, a first primary appendix epithelioid angiosarcoma with metastasis foci in the oral cavity. Objectives: To discuss the clinical, histological, and immunochemical features of an unusual case of intraoral angiosarcoma. Case report: A 53-year-old Saudi female with an uncommon clinical presentation of intraoral angiosarcoma. The patient reported the lesion being painless, slowly growing, and of a six-month duration. The microscopic examination and immunohistochemical evaluation showed epithelioid angiosarcoma. The tumor cells were positive to ERG, FLI 1, and CD31 (focal) and negative to CK HMW, CD45, S100, HMB 45, D2-4, and CD 34. Discussion: Due to the extremely rare occurrence and non-characteristic presentation of angiosarcoma in the oral cavity, many lesions maybe included in the differential diagnosis. Thus, making the diagnosis of intraoral angiosarcoma difficult.

Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

ABSTRACT: Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC.

Massive congenital cervicofacial desmoid-type fibromatosis in a 5-month-old infant.

Desmoid-type fibromatosis (DF) is a borderline tumor of soft tissues that has low malignant potential but described as infiltrative, locally aggressive and rapidly growing. In the pediatric population, it occurs in the head and neck. Presentation varies based on tumor size and location. Despite the high recurrence rate, surgical excision remains the modality of choice with. Here, we report a case of a 5-month-old boy, with extensive head and neck DF that was managed twice with conservative debulking surgery through a combined transoral-transcervical approach. On 2-year follow-up, he was gaining weight with no developmental delay and had no clinical evidence tumor regrowth.

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma.

BACKGROUND: Locally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined. METHODS: Retrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared. RESULTS: There was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001). CONCLUSIONS: CD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

Unusual Recurrent Lateral Canthus Mass in a 16-Year-Old Male Patient: Neurothekeoma.

Neurothekeoma (NTK) is a specific benign soft tissue tumor, typically involving the skin of the head and neck area as well as the upper part of the body in young age with female predominance. It has a typical lobular pattern of growth but often displays atypical features such as myxoid stroma or fascicular pattern, which makes the diagnosis more difficult and may necessitate the use of immunohistochemical staining to differentiate NTK from nerve sheath tumor. Ocular NTK in general is very rare with only 11 cases previously reported. We are presenting a case of recurrent mixed cellular/myxoid NTK involving the lateral canthal area of a 16-year-old-boy and we demonstrate the diagnostic challenge in such cases to attract the attention of ophthalmologists and pathologist to the rare occurrence of NTK in the ocular region.

Prevalence of Human Papillomavirus (HPV) Infection and the Association with Survival in Saudi Patients with Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) shows wide disparities, association with human papillomavirus (HPV) infection, and prognosis. We aimed at determining HPV prevalence, and its prognostic association with overall survival (OS) in Saudi HNSCC patients. The study included 285 oropharyngeal and oral-cavity HNSCC patients. HPV was detected using HPV Linear-Array and RealLine HPV-HCR. In addition, p16INK4a (p16) protein overexpression was evaluated in 50 representative cases. Oropharyngeal cancers were infrequent (10%) compared to oral-cavity cancers (90%) with no gender differences. Overall, HPV-DNA was positive in 10 HNSCC cases (3.5%), mostly oropharyngeal (21%). However, p16 expression was positive in 21 cases of the 50 studied (42%) and showed significantly higher OS (p = 0.02). Kaplan-Meier univariate analysis showed significant associations between patients' OS and age (p < 0.001), smoking (p = 0.02), and tumor stage (p < 0.001). A Cox proportional hazard multivariate analysis confirmed the significant associations with age, tumor stage, and also treatment (p < 0.01). In conclusion, HPV-DNA prevalence was significantly lower in our HNSCC patients than worldwide 32-36% estimates (p ≤ 0.001). Although infrequent, oropharyngeal cancer increased over years and showed 21% HPV-DNA positivity, which is close to the worldwide 36-46% estimates (p = 0.16). Besides age, smoking, tumor stage, and treatment, HPV/p16 status was an important determinant of patients' survival. The HPV and/or p16 positivity patients had a better OS than HPV/p16 double-negative patients (p = 0.05). Thus, HPV/p16 status helps improve prognosis by distinguishing between the more favorable p16/HPV positive and the less favorable double-negative tumors.

Laryngeal carcinoma in a father and son. Possible familial risk?

[No Abstract Available].

Acral dermatofibrosarcoma protuberans with myoid differentiation: A report of 2 cases.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade mesenchymal neoplasm with a tendency for local recurrence; it is rarely metastatic. Dermatofibrosarcoma protuberans typically arises in the trunk and proximal extremities. However, it can arise in unusual sites such as the hands and feet. Several variants have been described, including DFSP with myoid differentiation, which is very uncommon. This variant tends to be observed more with the fibrosarcomatous variant, and it can be either in the form of myoid bundles and nodules with no vascular relationship or represent hyperplastic blood vessels within the tumor. Here, we report 2 cases of DFSP with myoid differentiation (ordinary and fibrosarcomatous) on the foot. To the best of our knowledge, these cases represent the first 2 cases of acral DFSP with myoid differentiation.

Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

BACKGROUND: Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. METHODS: Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. RESULTS: The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003). CONCLUSION: Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society.

Solid-type primary intraosseous squamous-cell carcinoma in the mandible: Report of a rare case.

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant neoplasm that has an exquisitely exclusive affection to the jawbone. It is defined as squamous cell carcinoma arising within the jaw and developing from residual odontogenic epithelium or from a preexisting odontogenic cyst or tumor. The solid-type of this tumor is a central jaw carcinoma arising de novo and has no initial connection with the oral mucosa. Herein, we report a case of solid-type PIOSCC involving the mandible in a 37-year-old male patient elucidating its histopathological and imaging findings. The patient underwent surgical resection followed by post-operative adjuvant radiotherapy. The close 2-year follow up of the patient revealed neither locoregional nor distant metastasis.

Sampling modality influences the predictive value of grading in adult soft tissue extremity sarcomas.

CONTEXT: Histologic grade is one of the best predictors of outcome in adult soft tissue sarcomas. Current grading systems were validated on resection specimens; however, there has been a trend toward the use of biopsies to diagnosis these tumors. OBJECTIVES: To determine whether the grade of an extremity soft tissue sarcoma determined on tissue obtained by either core needle biopsy or incisional biopsy is predictive of metastasis- or disease-free survival, and whether either sampling modality is superior. DESIGN: One hundred three core needle biopsies and 107 incisional biopsies of nonmetastatic spindle cell sarcomas of the extremities were retrieved from the archives. All cases had a minimum 2-year follow-up. Patient data and outcome and tumor characteristics were recorded. Tumors were reviewed and evaluated using the French Federation of Cancer Centers Sarcoma Group grading system. Kaplan-Meier survival curves were generated to correlate tumor grade with metastasis- and disease-free survival for both groups. RESULTS: Patient and tumor characteristics were similar between groups except that more tumors were grade 3 and superficial in the incisional biopsy group. Grade determined on core needle biopsy was not predictive of either metastasis-free survival (P = .59) or disease-free survival (P = .50). In contrast, grade determined on incisional biopsy was predictive of both metastasis-free survival (P < .001) and disease-free survival (P = .001). CONCLUSIONS: Biopsy, particularly core needle biopsy, represents a convenient diagnostic tool, particularly in the context of neoadjuvant therapy. However, based on these results incisional biopsy is recommended if grading is to be used to predict prognosis in spindle cell soft tissue sarcomas of the extremities.

Papillary thyroid carcinoma-like tumor of the kidney: a case report.

Thyroid carcinoma-like tumor of the kidney is an extremely rare variant of renal cell carcinoma. Most previously reported cases were incidental finding; and none of them showed papillary thyroid carcinoma (PTC) nuclear features. This study reports the first case of PTC (follicular variant)-like tumor of the kidney in which a female patient presented with hematuria, weight loss, and flank pain. Imaging studies revealed a left renal mass with enlarged hilar lymph nodes. Histologically, the renal tumor had a striking resemblance to follicular variant of PTC. However, no radiological abnormalities were found in the thyroid, mediastinum, or pelvis. Tumor cells were negative for thyroid markers (thyroglobulin and TTF1). According to the authors, this is the first case of PTC (follicular variant)-like tumor of the kidney.