Triple-Negative Metaplastic Breast Carcinoma: Association of Epidermal Growth Factor Receptor Expression With Prognostic Parameters and Clinical Outcome.

Introduction Metaplastic breast carcinoma (MBC) is one of the rare special subtypes of breast carcinoma associated with poor prognostic features compared with invasive ductal carcinoma. Moreover, therapeutic options are limited in MBC owing to frequent triple-negative profiles of these tumors. Epidermal growth factor receptor (EGFR) is a proto-oncogene that is overexpressed in many human cancers, and is a potential therapeutic target. Therefore, in this study, we evaluated the expression of EGFR in MBC by immunohistochemistry, and its association with clinicopathological and prognostic parameters. Methods We conducted a retrospective observational study in the Department of Histopathology at Liaquat National Hospital and Medical College, Pakistan, over a period of seven years. A total of 61 cases with a histopathological diagnosis of MBC were included in the study. All slides were reviewed by histopathologists for diagnostic confirmation. Histopathological parameters, such as tumor size, grade, and nodal metastasis, were recorded. The representative tissue blocks were also retrieved and immunohistochemical studies were performed for cytokeratin 5/6 (CK5/6), Ki67, and EGFR. Results The mean age of the patients was 44.48 ± 13.01 years. The mean tumor size was 5.72 ± 2.72 cm, with most of the cases belonging to tumor (T)-stage T3. Axillary metastasis was present in 57.4% cases, and the perinodal extension was present in 11.5% cases. Most tumors were grade III (85.2%), with a mean Ki67 index of 39.67% ± 20.38%. Most of the cases were nonbasal (83.6%), owing to the absent CK5/6 expression. Tumor recurrence was noted in 14.8% cases, with a median follow-up of 43 (13-83) months and median disease-free survival of 36 (12-60) months. Positive EGFR expression was noted in 52.5% cases. A significant association of EGFR expression was noted with tumor grade, mean Ki67 index, axillary metastasis, and nodal (N)-stage. Cases with positive EGFR expression were found to have higher grade (grade III), with higher Ki67 index, higher frequency of axillary metastasis, and higher N-stage. Moreover, cases with positive EGFR expression had lower disease-free survival compared to cases with negative EGFR expression. Conclusion We found that a significant proportion of triple-negative MBC expressed EGFR. Moreover, EGFR overexpression was associated with poor pathological parameters and lower disease-free survival. Therefore, EGFR can be considered a potential prognostic biomarker and therapeutic target in triple-negative MBC; however, the correlation between gene amplification and protein overexpression is required to better uncover the role of EGFR as a therapeutic target.

CD30-Positive Anaplastic Variant of Diffuse Large B-cell Lymphoma: Frequency and Association With Clinicopathological Parameters.

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma and is the most common type of non-Hodgkin's lymphoma (NHL) worldwide. The World Health Organization (WHO) classification of hematopoietic tumors has recognized three morphological variants of DLBCL: centroblastic, immunoblastic, and anaplastic. Some studies have shown that the anaplastic variant of DLBCL is associated with aggressive clinicopathological features. Anaplastic DLBCL is rare, and the clinicopathological characteristics of this subtype of DLBCL are not widely studied in our population. Therefore, in this study, we evaluated the frequency of the anaplastic variant of DLBCL and its association with other clinicopathological parameters. Methods A retrospective study was conducted in the Department of Histopathology at the Liaquat National Hospital and Medical College over a period of six years, from January 2015 to December 2020. All cases diagnosed as DLBCL based on morphology and immunohistochemical (IHC) profile were included in the study. The diagnosis of anaplastic DLBCL was rendered based on morphology (large bizarre pleomorphic cells in a cohesive or sheet-like growth pattern), combined with CD30 IHC expression. Results The mean age of the patients was 52.90 ±16.42 years, and the mean Ki67 index was 73.18 ±16.52%. Of the 220 cases of DLBCL, 47.3% cases were germinal center B-cell (GCB) subtype, and 59.1% cases were nodal. BCL-2, BCL-6, MUM1, c-MYC, and CD10 positivity were noted in 60%, 45.5%, 40.9%, 44.1, and 38.6% cases, respectively. Only 14 cases (6.4%) were recognized as anaplastic variants of DLBCL according to the previously defined criterion. The only significant association of anaplastic-variant DLBCL was noted with a lack of BCL-2 expression. No significant association of anaplastic-variant DLBCL was noted with age, gender, Ki67 index, DLBCL subtype, or any other IHC marker expression. Conclusion We found a low frequency of the anaplastic variant of DLBCL in our study. No significant association of this DLBCL variant was noted with any of the clinicopathological parameters, except for the lack of BCL-2 expression. Alternatively, from a pathological perspective, it is important to recognize this variant of DLBCL as it often mimics other CD30-positive lymphoma and undifferentiated carcinoma.

Recurrence and Disease-Free Survival in Head and Neck Squamous Cell Carcinoma After Margin-Free Resection on Frozen Section: An Institutional Perspective.

Introduction The most important factor determining survival in patients with head and neck squamous cell carcinoma (HNSCC) is a disease recurrence. A high rate of recurrence was noted in previous studies conducted in Pakistan; however, these studies did not consider margin status as inadequate margin clearance leads to disease recurrence. In this study, we determined cancer recurrence in patients with HNSCC after nullifying this factor. Methods This cross-sectional observational study was conducted in Liaquat National Hospital (LNH) for a duration of three years. Data collection period was from January 2015 to December 2017. A total of 150 patients that underwent surgery at LNH for HNSCC with margin-free frozen sections were included in the study. Pathological tumor characteristics such as tumor type, size, depth of invasion and nodal status were determined. Results The mean age of the patients was 50.31±12.90 with mean tumor size of 3.38±1.76. Nodal metastases were present in 45.3% cases with 17.3% showing extranodal extension. Recurrence was observed in 66% of cases with median disease-free survival of 12 months and perineural invasion was noted in 12% cases. We found a significant association of disease recurrence with larger tumor size, depth of invasion and extranodal extension. Moreover, younger age (<30 years) and older age (>50 years) groups showed higher rates of recurrence than the middle age group (30-50 years). Similarly, univariate and multivariate analyses revealed that tumors with ≥1 cm depth of invasion and the presence of extranodal extension were more likely to have disease recurrence than tumors with <1 cm depth of invasion and without extranodal extension. Survival analysis using the Kaplan-Meier method for HNSCC revealed a significant difference in disease-free survival in patients with more than 2 cm tumor size and ≥1 cm depth of invasion than cases with ≤ 2cm tumor size and <1 cm depth of invasion. Conclusion A high rate of disease recurrence for HNSSC was noted in our study, despite margin-free primary tumor resection. Apart from tumor size and depth of invasion, extranodal extension was significantly associated with disease recurrence in HNSCC. This signifies a need for margin evaluation of neck dissection specimen in cases with extranodal extension.

Solid Papillary Carcinoma of Breast: Clinicopathologic Comparison With Conventional Ductal Carcinoma of Breast.

Introduction Solid papillary carcinoma (SPC) is a distinct rare subtype of breast tumour that often exhibits a neuroendocrine differentiation. Due to the rarity of these tumours, few studies have assessed the clinicopathological features of these tumours. Therefore, in this study, we evaluated the clinical and pathological profiles of SPC and compared the pathologic features with conventional invasive ductal carcinoma (IDC) in our population. Methods It was a retrospective cross-sectional study conducted at Liaquat National Hospital and Medical College from January 2013 until December 2019 over seven years. Cases with histological diagnosis of SPC and IDC were included in the study, and clinicopathological characteristics were compared. Results We included 39 cases of SPC in our study diagnosed during the study period. During the same timeline, 634 cases of IDC were reported and therefore included in the study for comparison. The mean age of the patients with SPC was 53.97 ± 12.15 years, and the mean tumour size was 3.42 ± 1.87 cm. Axillary metastasis was noted in 15.4% of cases. 94.9% of cases of SPC were invasive. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2/neu) and synaptophysin positivity was seen in 84.6%, 87.2%, 10.3%, and 59% respectively. Recurrence was noted in 10.3% of cases with 94.9% survival rate. Cases of SPC had significantly lower grade (grade I + II), tumour (T) and nodal (N) stage than IDC. Moreover, the frequency of hormonal receptor expression (ER and PR) was higher, and the frequency of human epidermal growth factor receptor 2 (HER2/neu) expression was lower compared to IDC. Conclusion SPC is a distinct variant of malignant papillary breast tumours with overall better prognostic parameters than IDC. Therefore, it is essential to recognize the histological features of this rare breast tumour.

Prognostic Implications of Deep Muscle Invasion and High Grade for Bladder Urothelial Carcinoma.

Introduction Urothelial carcinoma (UC) is the most common bladder cancer. The most censorious pathological aspect of UC is deep muscle invasion and tumor grade. In this study, we assessed the prognostic implications of tumor grade and deep muscle invasion in UC. Methods It was a retrospective cross-sectional study conducted at the Department of Histopathology, Liaquat National Hospital, from July to December 2019. The data were collected over five years from January 2014 till December 2018. Records from archives of the anatomic pathology were searched, clinical characteristics were recorded, and histopathological slides were reviewed. Histological parameters, including tumor grade and muscle invasion, were evaluated. Records of patient follow-up were assessed by reviewing clinical records. Recurrence of UC and overall survival was also recorded. Multivariate binary logistic regression was applied for variables that were significant on univariate logistic regression. Survival analysis was performed using the Kaplan-Meier method. Results The mean age of the patients was 63.39 ± 14.1 years. More than half (53%) cases were of low-grade papillary UC. Disease recurrence was observed in 53 (39.1%) patients, whereas the mortality rate was 16.6%. In our study, 49 (32.5%) patients were found to have deep muscle invasion. By multivariate analysis, we found that the deep muscle invasion was significantly associated with male gender and grade. In addition, a significant association of high-tumor grade with survival status of the patients was noted. Conclusions A high proportion of UC cases in our study were found to have deep muscle invasion and high-tumor grade. Moreover, a significant association of deep muscle invasion with tumor grade and an association of tumor grade with survival signify the prognostic value of these factors in UC.

Myoepithelial Carcinoma of the Floor of the Mouth: A Rare Salivary Gland Tumor in an Unusual Location.

Myoepithelial carcinomas are rare malignant salivary gland tumours encountered most commonly in the parotid gland and are amenable to surgical resection. However, when they occur at complex anatomical locations, complete resection becomes difficult due to their locally aggressive nature. Here we describe a case of a large myoepithelial carcinoma arising in the floor of the mouth and involving major structures at the skull base. A 30-year-old female presented with a slow-growing mass in the oral cavity. Computed tomography (CT) scan showed a heterogeneous appearing lesion in the mouth floor measuring 6.7 x 5.8 x 7.3 cm. Superiorly, the lesion was extending up to the skull base, laterally extending up to the parotid gland and inferiorly up to the submandibular gland. This lesion was also encasing the internal carotid artery. Incisional biopsy under local anaesthesia was performed, and the specimen was sent for histopathological analysis. Microscopic examination showed a neoplastic lesion composed of sheets of cells with oval nuclei and clear cytoplasm with a myxoid background. Immunohistochemical expression of pan-cytokeratin (CKAE1/AE3), p63, anti-smooth muscle actin (ASMA) and glial fibrillary acidic protein (GFAP) supported the diagnosis of myoepithelial neoplasm. The patient then underwent excision of the mass followed by histological analysis, which further showed microscopic evidence of infiltration into the surrounding tissue along with areas of atypia and significant mitoses. These morphological findings supported the diagnosis of myoepithelial carcinoma. The excised tumour was reaching up to the excision margin. Myoepithelial carcinomas are rare malignant tumours with diverse histomorphological patterns frequently present as a diagnostic challenge. The mainstay of treatment is complete surgical excision with disease-free margins, which can be challenging due to local aggressiveness and large size of these tumours. When these tumours occur in complex anatomical locations, complete excision becomes difficult, resulting in a dismal prognosis.

Rheumatoid arthritis clinical features and management strategies at an urban tertiary facility in Pakistan.

OBJECTIVE: To determine the presentation patterns, biologically vulnerable patient groups and treatment strategies of rheumatoid arthritis. METHODS: The retrospective study was conducted at the Rheumatology Clinic of Liaquat National Hospital and Medical College, Karachi, and comprised data of rheumatology patients who presented between September 2006 and September 2012. After screening all the files, rheumatoid arthritis cases were identified. Data collection was done using a questionnaire that included patient demographics, co-morbidities, clinical manifestations and drug therapy. SPSS 13 was used for statistical analysis. RESULTS: Of the 2300 files screened, 500(21.7%) related to patients of rheumatoid arthritis. The mean age at presentation of these 500 patients was 41±15 years. There were 367(73.4%) women and they presented at an earlier age compared to men (p<0.024). Erosions were present in 198(40%) patients on X-rays and 22(4.4%) had joint deformities. Seropositive rheumatoid arthritis was associated with higher erythrocyte sedimentation rate levels (p<0.014), but did not differ from seronegative rheumatoid arthritis in terms of Disease Activity Score-28 levels (p<0.21). CONCLUSIONS: The skewed gender distribution was likely an effect of rheumatoid arthritis biology rather than due to issues of healthcare accessibility. Seronegative RA is likely to present late though it is as destructive as the seropositive disease.