Asif Loya

Onsite cytopathology evaluation and ancillary studies beneficial in EUS-FNA of pancreatic, mediastinal, intra-abdominal, and submucosal lesions.

Endoscopic ultrasound‐guided fine needle aspiration cytology (EUS‐FNA) is considered to be a minimally invasive and safe technique, with low complication rates, for obtaining tissue samples from pancreatic lesions, and mediastinal and intra‐abdominal nodes. We retrospectively reviewed the diagnostic accuracy of this method at a tertiary care hospital in Pakistan.

Fine-Needle Aspiration Cytology in the Diagnosis of Pancreatic Neuroendocrine Tumors: A Single-Center Experience of 25 Cases

Objective: Pancreatic neuroendocrine tumors (Pan NETs) are rare but are being increasingly diagnosed. The objective of this retrospective study was to share our experience of fine-needle aspiration (FNA), including endoscopic ultrasound-guided FNA with rapid on-site evaluation (ROSE), with the use of immunohistochemical (IHC) markers in the diagnosis of Pan NET. Study Design: A total of 25 cases of Pan NET diagnosed on pancreatic FNA between 2008 and 2013 were identified from our hospital database. Clinical history, radiology, cytomorphological features, and IHC performed were reviewed. Results: The mean age of our patient group was 52 years; 15/25 were male. Most presented with abdominal pain and the majority of the lesions were in the pancreatic body, the largest being 14 cm in size. Based on the 2010 World Health Organization criteria, cases were further graded as follows: 21 cases were grade 1, 2 cases were grade 2 and 2 cases were grade 3. Proliferation marker Ki-67 was utilized in 6 cases for definitive grading. Of the 25 cases, 23 were diagnosed as nonfunctional while 2 were functional; 1 patient had MEN-1 syndrome and 1 had von Recklinghausens syndrome. Conclusions: Our data suggests that FNA, with ROSE and IHC markers, is highly sensitive and specific for diagnosing Pan NET.

Accuracy of diagnosis of solid pseudopapillary tumor of the pancreas on fine needle aspiration: A multi-institution experience of ten cases

Introduction: Solid pseudopapillary tumor of the pancreas (SPTP) is a neoplasm of uncertain origin and indolent biologic behavior with distinctive morphological features occurring predominantly in young women. This tumor has an excellent prognosis compared to neuroendocrine and acinar cell carcinoma, which are close differential diagnoses based on morphology, hence making it crucial to diagnose SPTP correctly. Objectives: To discuss the cytomorphological features of 10 cases of SPTP reported in two institutions and to evaluate the diagnostic accuracy of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) cytology in establishing the diagnosis of SPTP. Methods: Ten diagnosed cases of SPTP were retrieved from the computerized endoscopy and pathology databases of our two tertiary care institutions. Nine patients had subsequent histological follow-up available. Eight patients underwent EUS-FNA while one patient each had ultrasound and computed tomography-guided FNA. The rapid on-site evaluation was carried out in all 10 cases, and additional material was retained for cell block preparation. Immunohistochemical (IHC) stains ranging from synaptophysin, progesterone receptor, chromogranin, β-catenin, CD10, and NSE were applied on cell blocks. Histological sections of all resected specimens were reviewed, and findings were correlated with those obtained by FNA. Results: Adequate material was obtained in all ten cases. IHC stains helped to confirm the cytological impression of SPTP. Histological examination of resection specimens, available in 9/10 cases, confirmed the cytological diagnosis. Conclusions: FNA particularly that obtained with EUS guidance is an effective tool in the accurate diagnosis of SPTP.

Biliary Brush Cytology Revisited.

Purpose: To evaluate the diagnostic yield of biliary brush cytology and the factors affecting positive results in patients with biliary strictures. Patients and Methods: The medical records of all patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology at our institution from November 2004 to December 2013 were reviewed in this retrospective study. The yield of positive brush cytology and the factors affecting positive yield, such as stricture location, age, gender and preprocedure CA 19.9 level were assessed. The final histopathology, diagnosis obtained by other methods, such as endoscopic ultrasound-guided fine-needle aspiration cytology, CT scan, Tru-Cut biopsy and/or clinical/radiological follow-up were used to identify true- and false-positive/negative results. The brush cytology results were divided into 4 main categories: malignant, benign, atypical cells and inadequate. Results: A total of 1,168 patients underwent ERCP during this 9-year period. Out of these, 142 patients had ERCP and biliary brushings for diagnosis. The mean age of the patients at presentation was 58.7 years (range 23-84 years; 64.8% males). The indication for referral was obstructive jaundice in all patients. Of the 142 patients, 77 (54.2%) had a distal common bile duct (CBD) stricture and 65 (45.8%) had a proximal /complex hilar stricture. The strictures were classified as proximal or distal, based on their relationship with the cystic duct; those below the cystic duct insertion were classified as distal and those above it were considered proximal. The diagnostic yield of brush cytology was 58.5%. The diagnostic yield was higher for proximal than for distal CBD strictures (67 vs. 50%; p = 0.047). It was also higher for females (58 vs. 57.6%; p = 0.94), patients >50 years (60 vs. 50%; p = 0.29) and those with a CA 19.9 level >300 IU/ml (59.4 vs. 55.5%; p = 0.65) but did not reach statistical significance for any of these parameters. Complete follow-up data were available for 96 patients and 46 patients were lost to follow-up. The sensitivity, specificity, positive predictive value and negative predictive value were 65.3, 100, 100 and 27%, respectively. When patients with atypia were included in the group with positive results, the diagnostic yield increased to 65.5% with a diagnostic sensitivity of 68.6%. There were 27 false-negative diagnoses, 10 patients were true-negative and no patients had a false-positive diagnosis. Conclusion: Biliary brush cytology is a safe and simple initial diagnostic procedure in patients with biliary strictures and can be performed at the time of therapeutic ERCP. If performed correctly and then interpreted by a dedicated cytopathologist, it has a good diagnostic yield and sensitivity. We feel that the low rates of success with this technique reported in some earlier studies have led to a feeling that this is not a particularly useful technique. We recommend that this topic should be revisited, and that the technique should be used more often.

Patterns of pathologically confirmed metastasis to bone in Near East population

BACKGROUND Metastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly. METHODS A total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded. RESULTS Out of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations. CONCLUSION The patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis.

Contribution of BRCA1 large genomic rearrangements to early-onset and familial breast/ovarian cancer in Pakistan

BackgroundGermline mutations in BRCA1 and BRCA2 (BRCA1/2) account for the majority of hereditary breast and/or ovarian cancers. Pakistan has one of the highest rates of breast cancer incidence in Asia, where BRCA1/2 small-range mutations account for 17% of early-onset and familial breast/ovarian cancer patients. We report the first study from Pakistan evaluating the prevalence of BRCA1/2 large genomic rearrangements (LGRs) in breast and/or ovarian cancer patients who do not harbor small-range BRCA1/2 mutations.Materials and methodsBoth BRCA1/2 genes were comprehensively screened for LGRs using multiplex ligation-dependent probe amplification in 120 BRCA1/2 small-range mutations negative early-onset or familial breast/ovarian cancer patients from Pakistan (Group 1). The breakpoints were characterized by long-range PCR- and DNA-sequencing analyses. An additional cohort of 445 BRCA1/2 negative high-risk patients (Group 2) was analyzed for the presence of LGRs identified in Group 1.ResultsThree different BRCA1 LGRs were identified in Group 1 (4/120; 3.3%), two of these were novel. Exon 1–2 deletion was observed in two unrelated patients: an early-onset breast cancer patient and another bilateral breast cancer patient from a hereditary breast cancer (HBC) family. Novel exon 20–21 deletion was detected in a 29-year-old breast cancer patient from a HBC family. Another novel exon 21–24 deletion was identified in a breast-ovarian cancer patient from a hereditary breast and ovarian cancer family. The breakpoints of all deletions were characterized. Screening of the 445 patients in Group 2 for the three LGRs revealed ten additional patients harboring exon 1–2 deletion or exon 21–24 deletion (10/445; 2.2%). No BRCA2 LGRs were identified.ConclusionsLGRs in BRCA1 are found with a considerable frequency in Pakistani breast/ovarian cancer cases. Our findings suggest that BRCA1 exons 1–2 deletion and exons 21–24 deletion should be included in the recurrent BRCA1/2 mutations panel for genetic testing of high-risk Pakistani breast/ovarian cancer patients.

A novel deleterious c.2656G>T MSH2 germline mutation in a Pakistani family with a phenotypic overlap of hereditary breast and ovarian cancer and Lynch syndrome

BackgroundHereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS) account for a significant proportion of inherited gynecologic malignancies, mainly caused by pathogenic germline mutations in the BRCA1 and BRCA2 genes or in mismatch repair (MMR) genes, such as MLH1 and MSH2. Women harboring deleterious mutations in these genes have increased life-time risks of developing a number of malignancies including ovarian cancer. Since there is a phenotypic overlap of HBOC and LS, timely identification of individuals at-risk of a particular syndrome is crucial in order to optimize cancer risk management.Case presentationWe report a novel pathogenic MSH2 mutation, c.2656G > T, which was identified in a 67-year-old female patient with breast cancer, who had previously tested negative for a deleterious mutation in the breast cancer susceptibility genes BRCA1, BRCA2, CHEK2 or RAD51C. The patient reported a personal history of endometrial cancer diagnosed at age 48, and a strong family history of breast and ovarian cancer, as well as several other malignancies within the spectrum of LS. The novel mutation was also found in the index patient’s daughter and a niece, who were diagnosed with endometrial and ovarian cancer, respectively. Breast and endometrial tumors from c.2656G > T mutation carriers showed loss of MSH2 and MSH6 protein expression. The mutation was absent in the control population.ConclusionsOur finding suggests that testing for MMR genes may be of benefit to BRCA1/2 negative families with overlapping HBOC and LS phenotype in Pakistan. It is clinically significant to identify individuals harboring mutations in genes linked with a particular syndrome so that they can benefit from targeted life-saving cancer surveillance and preventive strategies.