Molecular and immunophenotypic characterization of anal squamous cell carcinoma reveals distinct clinicopathologic groups associated with HPV and TP53 mutation status.

Squamous cell carcinoma (SqCC) is the most common malignancy of the anal canal, where it is strongly associated with HPV infection. Characteristic genomic alterations have been identified in anal SqCC, but their clinical significance and correlation with HPV status, pathologic features, and immunohistochemical markers are not well established. We examined the molecular and clinicopathologic features of 96 HPV-positive and 20 HPV-negative anal SqCC. HPV types included 89 with HPV16, 2 combined HPV16/HPV18, and 5 HPV33. HPV-positive cases demonstrated frequent mutations or amplifications in PIK3CA (30%; p = 0.027) or FBXW7 mutations (10%). HPV-negativity was associated with frequent TP53 (53%; p = 0.00001) and CDKN2A (21%; p = 0.0045) mutations. P16 immunohistochemistry was positive in all HPV-positive cases and 3/20 HPV-negative cases (p < 0.0001; sensitivity: 100%; specificity: 85%) and was associated with basaloid morphology (p = 0.0031). Aberrant p53 immunohistochemical staining was 100% sensitive and specific for TP53 mutation (p < 0.0001). By the Kaplan-Meier method, HPV-negativity, aberrant p53 staining, and TP53 mutation were associated with inferior overall survival (OS) (p < 0.0001, p = 0.0103, p = 0.0103, respectively) and inferior recurrence-free survival (p = 0.133, p = 0.0064, and p = 0.0064, respectively). TP53/p53 status stratified survival probability by HPV status (p = 0.013), with HPV-negative/aberrant p53 staining associated with the worst OS, HPV-positive/wild-type p53 with best OS, and HPV-positive/aberrant p53 or HPV-negative/wild-type p53 with intermediate OS. On multivariate analysis HPV status (p = 0.0063), patient age (p = 0.0054), T stage (p = 0.039), and lymph node involvement (p = 0.044) were independently associated with OS. PD-L1 expression (CPS ≥ 1) was seen in 30% of HPV-positive and 40% of HPV-negative cases, and PD-L1 positivity was associated with a trend toward inferior OS within the HPV-negative group (p = 0.064). Our findings suggest that anal SqCC can be subclassified into clinically, pathologically, and molecularly distinct groups based on HPV and TP53 mutation status, and p16 and p53 immunohistochemistry represent a clinically useful method of predicting these prognostic groups.

Histopathological Characteristics and Prognosis of Malignant Acral Melanomas in Pakistani Patients.

Background Malignant melanoma is a common cancer in Scandanavian countries due to increased exposure to ultraviolet light. Very limited data is available on malignant melanomas in Pakistani population and further studies are needed to determine its incidence in our population. Objective The main objective of our study was to determine histopathological characteristics and prognosis of malignant foot melanomas in Pakistani patients. Material and methods After approval by the Institutional Review Board, we performed a retrospective study of 59 consecutive cases of malignant acral melanoma from the year 2016-2019. The follow-up of in-house cases was available in hospital archives. The follow-up of diagnostic patients was done through direct communication. The histological features were assessed, and the prognosis was determined in terms of recurrence, metastasis, and death. Results The main histological features assessed were Breslow thickness <1 (n=3), >1-2 (n=9), >2-4 (n=12), >4 (n=36), ulceration was present in 65% (n=39), and pathological stage 1 (n=3), stage 2 (n=9), stage 3 (n=12) and stage 4 (n=36). The margin was involved in 28.3% (n=17) cases. Recurrence was observed in 47.4% (n=28), metastasis in 55.9 % (n=33), and death was observed in 49.1% (n=29). The mean follow-up duration of 3.4 years ± 0.20 (Range 3 to 6 years). The recurrence-free survival was 2.9 ± 0.24 years, metastasis-free survival was 2.8 ± 0.237 years, and disease-specific survival was 3.4 ± 0.203 years.  Conclusion Malignant acral melanoma is fatal with high mortality rates. In our part of the world, acral melanoma has poor prognosis compared to non-acral melanomas. When compared with acral melanomas in other parts of the world prognosis is even worst. Early diagnosis and treatment are crucial in terms of patient management.

Hepatic Epithelioid Angiomyolipoma Treated with Laparoscopic Resection: Case Report and Review of the Literature.

Hepatic angiomyolipoma is a rare primary liver tumor, with a radiographic appearance very similar to hepatocellular carcinoma. We present the case of a noncirrhotic patient with a liver tumor suspicious for HCC by imaging features. Liver biopsy demonstrated angiomyolipoma, and the patient successfully underwent a laparoscopic liver resection.

The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors.

BACKGROUND: There has been much controversy regarding the accuracy of grading pancreatic neuroendocrine tumors (PNETs) on fine-needle aspiration (FNA) biopsy. The objectives of this study were to evaluate whether grading according to the fraction of Ki-67-positive tumor cells (the Ki-67 proliferation index) on material from endoscopic ultrasound-guided FNA biopsies correlated with grading on surgical resection specimens and to evaluate the minimum amount of FNA material needed. METHODS: A case series of 27 PNETs with FNA biopsies and corresponding surgical resection specimens at the authors' institution were evaluated. Tumors were graded on FNA and surgical specimens with an evaluation of Ki-67 index according to 2010 World Health Organization criteria. Chart reviews were conducted to evaluate recurrence or clinical progression in patients who were being managed conservatively with observation. RESULTS: The evaluation of grading between FNA and tumor resection specimens revealed that 22 of 26 FNA specimens (84.6%) had Ki-67 results comparable to those in the corresponding surgical resection specimens, thus allowing for accurate grading. Correct FNA diagnosis with the ability to distinguish between grade 1 and 2 tumors had a positive predictive value of 88.9%, with 72.7% sensitivity, 93.3% specificity, and a P value of .00081. In addition, 24 of 26 cases contained less than 2000 cells, of which 20 were correctly graded on FNA material. Seven of 26 FNA samples had less than 1000 cells, of which 6 were correctly graded, including 2 that had only 50 cells. CONCLUSIONS: The current results exhibit good correlation between FNA grade and final grade on surgical resection specimens using Ki-67 index, even in samples with less than the recommended total cell count. Therefore, grading of PNETs on FNA with the Ki-67 proliferation index should be assessed and is a practical parameter to report to clinicians. Cancer Cytopathol 2018;126:170-8. © 2017 American Cancer Society.

An Intact Dissecting Baker's Cyst Mimicking Recurrent Deep Vein Thrombosis.

We report a case of a 75-year-old female with a history of acute deep vein thrombosis (DVT) 6 years ago who presented with unilateral calf swelling and pain. D-dimer was normal, and compression ultrasound revealed findings typical of DVT, including an incompressible dilated and hypoechoic peroneal vein. Despite 4 months of anticoagulation for supposed recurrent DVT, pain symptoms persisted and repeat D-dimer and compression ultrasound were unchanged. A magnetic resonance imaging scan to investigate the leg demonstrated a 6-cm dissecting Baker's cyst extending posterolaterally resulting in venous compression and distal dilation, which appeared to have been confused with a DVT. Ultrasound-guided aspiration of the cyst provided immediate and sustained relief. Herein we provide a review of the literature for the management of this rare scenario.

Metastatic Renal Cell Carcinoma in a Hepatic Hemangioma: A Case Report and Review of the Literature.

We report the case of 55-year-old female with biopsy-proven clear cell renal cell carcinoma with a suspicious lesion found in the liver who presented for right radical nephrectomy and partial hepatectomy. Histologic evaluation of the hepatic specimen demonstrated metastatic renal cell carcinoma within a hepatic hemangioma. Herein we provide a review of the literature for this uncommon scenario.

Temporal trends in outcome of oral squamous cell cancer in a resource-limited setting.

AIMS AND BACKGROUND: Improving survival has been documented for oral squamous cell carcinoma in recent years. It is a common malignancy in Pakistan but survival outcomes have not been reported. The objective of this study was to determine survival and identify independent predictors in patients with oral squamous cell cancer in 2 different time periods. METHODS: A retrospective review of patients who received treatment between 2003 and 2012 was performed. Patients were divided into two 5 year groups: group 1 (2003-2007) (n = 628) and group 2 (2008-2012) (n = 920). Demographics, risk factors, treatment approaches, and outcomes were compared. Disease-free and overall survival were calculated. Cox proportional hazard model was used to determine independent predictors of survival. RESULTS: A significant difference was present for ethnicity and grade and clinical T and N stage of tumors, with earlier presentation in group 2. More patients underwent surgery (p = 0.001) and had radical treatment intent (p<0.0001) in recent years. Induction chemotherapy (p<0.0001) and palliative chemotherapy (p<0.0001) were used more frequently. No significant difference in disease-free survival was observed but overall 5-year survival improved significantly (23% vs 42%) (p<0.0001). Use of palliative chemotherapy reduced risk of death significantly (hazard ratio [HR] 0.1, confidence interval [CI] 0.02-0.4, p = 0.003), while pathologic nodal positivity significantly increased the risk (HR 2.5, CI 1-5.9, p = 0.03). CONCLUSIONS: These results from a single cancer hospital demonstrate improvement in overall survival secondary to early detection, better patient selection, and use of palliative chemotherapy in the later period.

Five-year follow-up of concomitant accelerated hypofractionated radiation in advanced squamous cell carcinoma of the buccal mucosa: a retrospective cohort study.

In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC) are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC) regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m(2)). Five-year overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were determined. Based on AJCC staging, 7 (11%) patients were stage III, 31 (49%) stage IV a, and 25 (40%) stage IVb at presentation. After IC, 8 (18%) patients had complete radiological response, 33 (73%) had partial response, and 4 (9%) had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62%) patients were complete responders and 24 (38%) had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.