Clinical, Histopathologic Features and Outcome of Breast Cancer in UK Women of Ethnic Origin.

OBJECTIVE: Breast cancer (BC) in non-Caucasian females is understudied and its management is based on Caucasian data. 30 % of the West Midlands females are non-Caucasian. We aimed to elucidate the pathologic features, molecular profile, and outcome of non-Caucasian breast cancer. METHODS: Breast cancers (BCs) of different ethnic origins diagnosed at a large Birmingham tertiary referral hospital between 2000 and 2016 were identified. Detailed clinical and histological data were collected and statistically analyzed. RESULTS: Out of 7554 BC cases, 749 were of ethnic ancestry and median age of 51 years. These comprised 47 in-situ and 702 invasive carcinomas of presenting symptomatically in 86.2% of patients. 53.4% of the invasive carcinomas measured >20 mm. Cancers were predominantly of grade 3 (45%), and grade 2 (42.4%). Median NPI was 4.35. 65.1% of the ethnic carcinomas were of luminal subtype, 18.6% were Her2 positive and 16.2% triple-negative. Median overall survival was 62 months. Five and ten-year survival was 81.7% & 68.4% respectively. Ethnicity correlated with higher NPI (p <0.001), larger tumour size (p= 0.001) and larger number of positive axillary nodes (p=0.007). Negative correlations were found between age at diagnosis and both invasive tumour size & grade (p< 0.001) and between tumour grade and overall survival (p= 0.006). CONCLUSION: Compared with Caucasian breast cancer, non-Caucasian tumours presented predominantly symptomatically at younger age, were of larger size, higher grade with more unfavorable phenotypes and shorter survival. This is important in counselling, planning management and follow up of non-Caucasian patients.

Inter-observer reproducibility of the Royal College system for reporting thyroid cytology: Experience of the Egyptian National Cancer Institute.

PURPOSE: To assess the inter-observer agreement between 3 cytopathologists of thyroid FNAC using Royal College of Pathology reporting system. PATIENTS AND METHODS: The study is a retrospective one conducted on 204 cases retrieved from the archives of the Cytology Unit, Pathology Department, National Cancer Institute, Cairo University during the time period from January 2016 to December 2016. Cases were diagnosed separately by 3 cytopathologists using the Royal College of Pathology classification system (RCPath), where Thy1, nondiagnostic; Thy2, nonneoplastic; Thy3a, atypical, Thy3f, follicular lesion; Thy4, suspicious of malignancy; and Thy5, malignant. Kappa statistics were used where combination of the agreement between the 3 observers simultaneously was done. RESULTS: There was a good overall agreement between the three observers regarding all categories (kappa statistics was 0.679). Perfect agreement was reported for Thy5 category (κ = 0.874), good agreement was observed for Thy1 and Thy2 (κ = 0.784 and 0.719, respectively). For Thy3a, Thy 3f and Thy 4, a moderate agreement was reported (κ = 0.407, 0.446 and 0.453 respectively). Combination of surgical categories (Thy3f, Thy4, and Thy5) achieved a good agreement (κ = 0.701) as well as for non-surgical categories (Thy1, Thy2, and Thy3a) (κ = 0.712). CONCLUSION: RCPath reporting system for thyroid FNAC is clinically applicable and can be used for differentiation between benign cases needing observation and follow up on one hand, and malignant cases requiring surgical intervention on the other. The least inter-observer agreement (moderate agreement) was detected for Thy3a, Thy3f and Thy4 categories, necessitating multidisciplinary team meeting before any clinical decision.

The role of S100P and IMP3 in the cytologic diagnosis of pancreatic adenocarcinoma.

PURPOSE: The aim of this study was to assess the role of the two markers, S100P and IMP3, in differentiating between pancreatic ductal adenocarcinoma (PDA) and non-neoplastic pancreatic tissue in (fine needle aspiration cytology) FNAC. PATIENTS AND METHODS: This is a retrospective study that included 72 cases presented with pancreatic mass, where endoscopic guided FNAC was taken from pancreatic lesions. The final histopathologic diagnosis was considered the gold standard. Cell blocks were stained with anti S100P, and IMP3. Nuclear immunoreactivity with or without cytoplasmic staining for the first marker, and cytoplasmic staining for the second marker was considered specific. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and total accuracy of the two markers, as well as the combined accuracy of both markers were calculated. RESULTS: S100P achieved 96.4% sensitivity, 93.3% specificity, 98.2% PPV, 87.5% NPV and 95.8% total accuracy, while IMP3 achieved 91.2% sensitivity, 86.7% specificity, 96.2% PPV, 72.2% NPV and 90.3% total accuracy for PDA. Both markers showed a total combined accuracy of 89%. S100P showed strong and diffuse staining pattern in most of cases, while the staining pattern for IMP3 was moderate and focal in most of cases. CONCLUSION: Both markers were sensitive and specific for diagnosis of PDA. The staining pattern for S100P was easier to evaluate than IMP3.

The role of Napsin-A and Desmocollin-3 in classifying poorly differentiating non-small cell lung carcinoma.

UNLABELLED: There is increased need for classification of non-small cell lung cancer (NSCLC) into its major subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). Such a classification is enabled in poorly differentiated tumours based on routine morphology due to overlapping morphologic features. In such cases, the use of immunohistochemistry (IHC) can differentiate between the two subtypes. PURPOSE: To test the ability of the two markers; Napsin-A and Desmocollin-3, in differentiating poorly differentiated (AC) from poorly differentiated SCC in small biopsies. PATIENTS AND METHODS: This is a retrospective study including 60 patients who presented with pulmonary nodules. Cases with biopsy specimens diagnosed as poorly differentiated non-small cell lung cancer, and had corresponding resection specimens were included. Cell blocks were stained with anti Napsin-A, and anti Desmocollin-3. Cytoplasmic immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, total accuracy and combined accuracy of both markers were calculated. RESULTS: Napsin A showed a sensitivity of 89.3%, a specificity of 96.9%, PPV of 96.2%, NPV of 91.2%, and a total accuracy of 93.3% for AC, while Desmocollin-3 achieved 90.6% sensitivity, 96.4% specificity, 96.7% PPV, 90% NPV, and 93.3% total accuracy. Both markers achieved a total accuracy of 90%. CONCLUSION: Napsin-A, and Desmocollin-3 were sensitive and specific markers for the diagnosis of AC and SCC, respectively. Both markers allowed classification of 54/60 cases into either AC or SCC.

Role of thyroid transcription factor-1 and P63 immunocytochemistry in cytologic typing of non-small cell lung carcinomas.

PURPOSE: Evaluation of the value of thyroid transcription factor (TTF-1) and P63 in subtyping of non-small cell lung cancer in cytologic material. PATIENTS AND METHODS: This is a retrospective study including 40 cases of primary lung lesions who underwent image guided FNAC from pulmonary nodules. The final histopathologic diagnosis was the gold standard. Cell blocks were stained with anti-TTF-1, and P63. Nuclear immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, of the cytologic diagnosis and of the two markers, as well as the accuracy of the combined markers were calculated. RESULTS: Cytomorphology achieved a sensitivity of 83.3%, specificity of 91%, PPV of 91%, and NPV of 83.3%, for the diagnosis of AC, and 91% sensitivity, 83.3% specificity, 83.3% PPV, and 91% NPV, for the diagnosis of SCC. The concordance between cytologic and histopathologic diagnoses of AC and SCC was 87%. TTF-1 achieved 87.5% sensitivity, 94.7% specificity, 95.5% PPV, and 85.7% NPV for AC, while P63 achieved 94.7% sensitivity, 95.8% specificity, 94.7% PPV, and 95.8% NPV for SCC. TTF-1 enhanced the sensitivity of cytomorphology for AC from 83.3% to 87.5%, and specificity from 91% to 94.7%. Similarly P63 enhanced the sensitivity for SCC from 91% to 94.7%, and specificity from 83.3% to 95.8%. CONCLUSION: TTF-1 achieved moderate sensitivity, and high specificity in the diagnosis of AC, while P63 was highly sensitive and specific for the diagnosis of SCC. Immunocytochemistry raised the sensitivity and specificity of FNAC in diagnosing AC and SCC using TTF-1 and P63, respectively.

The validity of immunocytochemical expression of cyclin D1 in fine needle aspiration cytology of breast carcinoma.

PURPOSE: The aim of this work is to study the validity of cyclin D1 expression, a cell cycle regulatory protein, on (fine needle aspiration cytology) FNAC samples in patients with breast carcinoma using immunostaining technique. PATIENT AND METHODS: This is a study done on 70 patients with primary breast carcinoma, presented to Cytology Unit, Pathology Department, National Cancer Institute, Cairo University. They underwent preoperative FNAC and diagnosed as breast carcinoma. The cytologic and tissue section slides were subjected to cyclin D1 immunocytochemical staining. Only the nuclear immunoreactivity for cyclin D1 was considered specific. The rate of concordance, and discordance, and kappa value were calculated. Relation between cytologic expression of cyclin D1 and different clinicopathologic parameters was evaluated. RESULTS: Cyclin D1 immunocytochemical expression was observed in 53/70 cases (75.7%) in cytologic smears. In histologic sections of the corresponding cases, cyclin D1was detected in 48/70 cases (68.6%). The concordance rate of cyclin D1 expression in the FNA and histologic sections was 87.1% while the discordance rate was 12.9%. Kappa showed a value of 0.65. A statistically significant relation was found between cyclin D1 immunocytochemical expression and hormonal status as well as nuclear grade. CONCLUSION: Cyclin D1 immunocytochemical expression can be performed successfully on cytologic samples with a high concordance rate and agreement with histologic results. This can help in determining tumor biology, and plan for patients' treatment. The marker showed a significant relation with hormone receptor status and nuclear grade.

Diagnostic accuracy and pitfalls of preoperative fine needle aspiration cytology in salivary gland lesions.

PURPOSE: Evaluation of diagnostic accuracy of preoperative fine needle aspiration cytology (FNAC) in salivary gland lesions. PATIENTS AND METHODS: This is a retrospective study of 82 patients presented at NCI, Cairo University with salivary gland lesion who underwent preoperative FNAC diagnosis with subsequent excision and histopathologic assessment. Cytology results were classified as negative, positive, suspicious for cancer and inadequate. The definitive histopathologic report according to WHO Histological typing was the gold standard diagnosis against which FNAC was compared. RESULTS: Our study included 82 patients who underwent preoperative FNAC of major salivary glands with subsequent surgical excision. Male to female ratio was 1.4: 1. The median age was 42 years. Parotid gland was involved in (68.3%), submandibular in (28%) and submental gland in (3.7%). Forty cases (48.8%) were cytologically diagnosed as benign lesions, 26 (31.7%) were malignant and 10 (12.2%) were suspicious. Cytological findings were nondiagnostic in 6 (7.3%). The most common benign cytologic diagnosis was pleomorphic adenoma; 16 out of 40 cases (40%), while the most common malignant tumor was carcinoma; 22 out of 26 cases (84.6%). Cytologic diagnoses were compared with histopathologic ones and were true-negative in 37 (92.5%), true-positive in 33 (91.6%), false-negative in 3 (8.3%) and false-positive in 3 (7.5%) cases regarding detection of malignant tumors. The cytologic diagnosis achieved a sensitivity of 91.7%; a specificity of 92.5%, PPV 91.6%, NPV 92.5% and diagnostic accuracy 92%. The rates of agreement of histopathologic type for benign and malignant tumors were 89.2% and 91%, respectively. CONCLUSION: The sensitivity, specificity and diagnostic accuracy of FNAC were 91.7%, 92.5% and 92%, respectively. Attention to subtle morphologic changes, pitfalls and limitations are important to increase diagnostic accuracy. Multidirectional aspiration is preferred to avoid selective sampling. Re-aspiration of solid portion after cyst fluid aspiration is necessary to decrease the rate of inadequacy. KEY WORDS: FNAC - Salivary gland lesions - Accuracy - Pitfalls.