Role of SOX10 Immunohistochemical Expression in Diagnosing Triple Negative Breast Cancer and Its Correlation With Clinicopathological Features.

BACKGROUND: Triple-negative breast cancer (TNBC) poses a diagnostic challenge for histopathologists due to the reduced frequency of breast-specific markers. SOX10 has emerged as a useful diagnostic marker for TNBC. The aim of our study was to determine the frequency of SOX-10 immunohistochemical (IHC) expression in our cohort and assess its correlation with clinicopathological and histological features. MATERIALS AND METHODS: We included 72 primary TNBC cases. Specimens included tru-cut biopsies and excision specimens. We stained whole slide sections of these specimens with SOX10 antibody and calculated its frequency (%) of expression and H-score. We applied the chi-square test to assess the correlation between SOX10 expression and clinicopathological and histological features such as the patient's age, specimen type, tumor size, histological type, histological grade, nuclear pleomorphism, mitotic count, tumor-infiltrating lymphocytes (TILs), necrosis, calcification, lymphovascular invasion (LVI), lymph node involvement, T stage, and N stage. RESULTS: SOX10 expression was observed in 42 (58.3%) cases with a median H-score of 57.5. The expression was significantly higher in tru-cut biopsy specimens as compared to excision specimens (73.5 vs 41.7%) and TILs negative tumors as compared to TILs positive tumors (64.3% vs 27.3). Metaplastic carcinoma showed reduced expression when compared with non-metaplastic tumors (35.7% vs 63.8%), but statistical significance was not achieved. No correlation was observed with the patient's age, tumor size, histological type, histological grade, nuclear pleomorphism, mitotic count, necrosis, calcification, LVI, lymph node involvement, T stage, and N stage. CONCLUSION: SOX10 was expressed in more than half of the TNBC cases of our study which not only highlights its diagnostic utility but advocated its application in combination with other breast-specific markers. The expression didn't correlate with the majority of clinicopathological and histological features, but correlation with tru-cut biopsy specimens and absence of TILs draws attention towards possible roles of proper fixation and host immunity, respectively.

Reflection of mentors and mentees at initiation of Faculty Mentorship Program at Aga Khan University: A perspective.

Objectives: To explore perception of mentors and mentees about 'Mentorship Program at Aga Khan University Medical College (AKU-MC) from a structured feedback form. Methods: A retrospective study was conducted for evaluation of mentorship program at AKU-MC during the period from Jan 2019 to March, 2021. Responses on validated "Pre-intervention Probe Forms", from forty-seven mentors and fourteen mentees inducted in the program were reviewed. Confidentiality and anonymity of data were deliberated. All replies to each question were entered in a separate worksheet to determine the frequency and percentage of answers. Responses conveying same message, but worded differently were then grouped. Results: All the mentees (n=14) responded positively to the question on the "understanding of the mentoring program. The mentees (n=12, 86%) recognized the potential of the program to transfer knowledge and skills, (n=11, 79%) supported its role for achievement of goals, (n=7, 50%), acknowledged its role in faculty relationships. The mentors expressed their enthusiasm to help the mentee's in their professional development. They (n=20, 43%) offered support to set career goals, (n=29, 62%) proposed transfer of knowledge, skills, and experiences to achieve goals, (n=15, 32%) decided to be "role models". Some (n=10, 21%) forecasted improved communication skills, (n=14, 30%) boosted leadership capabilities, (n=13, 28%) expected improved work performance, (n=15, 32%) opinioned that networking and leadership qualities will impact the growth of the mentee to meet the university's expectations. Conclusion: Both mentors and mentees recognized the importance of the faculty mentorship program at AKU-MC for professional guidance, development and improvement in work performance.

Primary Follicular Dendritic Cell Sarcoma of Breast: 2 Further Cases with Review of the Literature.

Follicular dendritic cell sarcoma (FDCS) is a tumor derived from antigen-presenting cells and can occur within lymphoid tissue or at extranodal sites. FDCS of the breast is remarkably rare, with only 4 cases previously reported in literature. FDCS appears grossly as a well-circumscribed, firm mass with a grey-yellow surface, areas of necrosis, and histologically comprises of spindled, oval, or epithelioid cells with intensely eosinophilic cytoplasm. Immunohistochemistry plays a key role in its diagnosis. Here we describe 2 cases of FDCS of breast in 2 women aged 70 and 35 years old, who presented with a palpable lump in the breast. One patient had concomitant invasive ductal carcinoma as well. We highlight the key histopathological and immunohistochemical features of the tumor.

Thyroid cytology in Pakistan: An institutional audit of the atypia of undetermined significance/follicular lesion of undetermined significance category.

INTRODUCTION: Fine needle aspiration cytology (FNAC), along with thyroid ultrasound, is an important tool in evaluation of thyroid nodules that helps in further management of these patients in making a decision of surgical intervention vs follow-up. The Bethesda System for Reporting Thyroid Cytopathology category III of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) has risk of malignancy (ROM) ranging from 5% to 15%. The aim of the present study was to describe the frequency of AUS/FLUS in thyroid gland FNACs and the surgical outcomes of these cases. METHODS: The integrated laboratory management system retrieved the thyroid FNACs from 2010 to 2018 and subsequent surgical pathology specimens. For the AUS/FLUS cases, data regarding patient demographics, cytology and histological diagnoses were recorded. The results were tabulated as the overall frequency of AUS/FLUS in thyroid FNACs, cytohistological correlation (benign and malignant) and ROM. RESULTS: Over a period of 9 years, 256 (10.9%) cases out of 2342 thyroid FNACs were reported as AUS/FLUS at our institution. Mean age was 43.5 years. The majority (70.3%) of patients were female. Seventy-two of 104 resection specimens (69.2%) were reported as benign and 32 cases (30.7%) had malignant diagnosis. Upper-bound ROM was 30.7% (32 cases with malignant diagnosis out of 104 resection specimens). Lower-bound ROM was calculated as 12.5% (32 cases with malignant diagnosis out of 256 total AUS diagnosis). CONCLUSION: The AUS/FLUS category of thyroid cytology and associated ROM remain an evolving area. Individual institutions should monitor the frequency and include ROM in the dashboard indicators to remain within the recommended range.

Encapsulated papillary carcinoma of breast; a clinicopathological study of 25 cases and literature review with emphasis on high grade variant.

Encapsulated Papillary Carcinoma (EPC) is a rare breast tumor with excellent prognosis. Treatment and stage of EPC is influenced by invasion and high nuclear grade. Our aim was to study the clinicopathological features of EPC, especially high grade tumors and to compare the features of invasive and non-invasive tumors. We reviewed clinicopathological features of 25 cases of EPC diagnosed at our institution from 2006 till 2020. Patients' age ranged from 21 to 75 years (median 55 years). Tumor size ranged from 1 to 9 cm (median 3.5 cm). Overall, invasion was present in 44% cases. High nuclear grade was observed in 24% cases. Majority of these high grade tumors were below 40 years. All of these tumors were 4 cm or larger in size. Two third of these tumors were invasive. Hormone receptor negativity and lymph node involvement was observed in 1 out of 3 cases, when performed. Clinicopathological and histological features of invasive and non-invasive tumors were compared and only lymph node involvement was found to be significantly more frequent in invasive tumors (p = 0.049). Median follow up duration was 18 months. All patients were alive and disease free except for a single patient who died of cerebrovascular accident. EPC has excellent clinical course. Invasion and high nuclear grade should be carefully searched for as these features determine tumor stage and treatment.

Invasive Breast Carcinoma Arising in a Nipple Adenoma After 15 Years: Report of a Rare Case and Literature Review.

Nipple adenoma (NA) is a rare benign breast neoplasm that seldom co-exists with breast carcinoma (BC). Majority of these BC are separate from NA, and their origin from NA is an extremely rare event. We herein describe a case of 65-year-old female who had a painless lump for 15 years which increased in size and ulcerated for last six months. Microscopic examination of the wedge biopsy of nipple showed features of NA at superficial aspect and invasive carcinoma from it at the deeper aspect. The patient underwent mastectomy and axillary clearance, which revealed a 4-cm invasive breast carcinoma, no special type with axillary lymph node involvement. The patient received adjuvant chemotherapy, radiotherapy and adjuvant hormonal therapy. The patient is alive and disease-free after 36 months. NA should be carefully evaluated for co-existent BC because it completely changes the treatment plan and prognosis.

Dedifferentiated Liposarcoma With Meningothelial-Like Whorls: Five Additional Cases and Review of the Literature.

Background. Diagnosis of dedifferentiated liposarcoma (DDL) can sometimes be challenging due to a wide variety of histological features. "Meningothelial-like" whorl is an uncommon histological feature of DDL, which is also observed in neural tumors and follicular dendritic cell sarcoma. This feature is frequently associated with metaplastic bone formation. We conducted this study to describe the clinicopathological features of DDL with meningothelial-like whorls that would aid in establishing accurate diagnosis. Material and Methods. Microscopic glass slides of 5 cases of DDL with meningothelial-like whorls, diagnosed between January 2010 and December 2019, were reviewed. Results. Paratesticular region was the most common site. Whorls occupied 10% to 75% of tumor area and ranged in size from <0.1 cm to >2 cm. In 1 case, these whorls coalesced to form large areas of dedifferentiation. The cells forming whorls were spindle to epithelioid shaped and lacked significant nuclear pleomorphism and increased mitoses. Metaplastic bone formation was observed in 4 cases and cartilage formation in 3 cases. p16 and α-smooth muscle actin (α-SMA) immunohistochemical stains were positive in 2 cases, when performed. MDM2 gene amplification was observed in all cases by fluorescence in situ hybridization technique. These tumors showed aggressive behavior, similar to that of DDL without meningothelial-like whorls. Two patients died, 1 developed recurrence, 1 presented as recurrent tumor, and 1 developed metastasis. Conclusion. Meningothelial-like whorls in DDL most likely represent an early stage of dedifferentiation. Presence of well-differentiated liposarcoma areas, metaplastic bone formation, positive expressions for p16 and α-SMA immunohistochemical stains, and MDM2 gene amplification are useful diagnostic clues. These tumors have the potential to behave aggressively.

Solid papillary carcinoma of breast; a detailed clinicopathological study of 65 cases of an uncommon breast neoplasm with literature review.

Solid papillary carcinoma (SPC) is an uncommon breast tumor whose prognosis depends on invasive component. We studied clinicopathological features of SPC by reviewing 65 cases. Invasive component was seen in 75.4% cases. Almost all tumors with grade III nuclei had invasive component. Mean patients' age of invasive tumors was significantly higher than that of non-invasive tumors (P = .036). All patients were alive and disease free except for a single patient who developed distant metastasis and died of disease. SPC have excellent clinical course. Careful search for invasive component is mandatory, especially in tumors with older patient's age and higher nuclear grade.

Synchronous Well-differentiated Endometrioid Adenocarcinoma and Leiomyosarcoma of the Uterus With Pulmonary Metastasis in a 50-Yr-Old Woman: A Case Report and Review of Literature.

The most common synchronous gynecologic malignancies are endometrial and ovarian cancers. However, synchronous endometrial adenocarcinoma and uterine leiomyosarcoma are extremely rare. We report the case of a 50-yr-old woman who was diagnosed with concomitant endometrial adenocarcinoma and uterine leiomyosarcoma. The sarcomatous neoplasm was positive for anti-smooth muscle actin and CD10, and focally positive for Cytokeratin AE1/AE3 and Cytokeratin Cam 5.2. She underwent total abdominal hysterectomy with bilateral salpingoopherectomy followed by radiation, brachytherapy, and chemotherapy. Three years later, she presented with cough and dyspnea and was found to have pulmonary metastasis. These tumor cells were positive for anti-smooth muscle actin, Cytokeratin AE1/AE3, Cytokeratin Cam 5.2, and epithelial membrane antigen, and therefore a diagnosis of lung metastasis from myometrial leiomyosarcoma was made. She received chemotherapy postoperatively. Currently, the patient has multiple lung metastases, is on Megestrol Acetate and is clinically well. This is the first reported case of concomitant uterine malignancies with pulmonary metastases and a long follow-up of 9 yr. It is important to rule out carcinosarcoma as a differential diagnosis in such patients.

High Grade Encapsulated Papillary Carcinoma of Breast in a Young Female.

Encapsulated papillary carcinoma (EPC) is a special type of papillary breast lesion known to be of low and intermediate grade. But recent data suggests existence of such tumors with high nuclear grade and mitotic index rendering them aggressive with chances of recurrence and lymph node metastasis which may alter the management of this tumor. Here, we present a case of a high grade encapsulated papillary carcinoma in a 22-year female who had a history of painful swelling in the upper outer quadrant of right breast with tender lymph nodes in the lower axilla. The subsequent radiologic findings showed a solid mass with cystic component and the patient underwent wide local excision along with excision of lymph nodes. Microscopy revealed a high-grade encapsulated tumor with papillary features; and a diagnosis of high grade encapsulated papillary carcinoma was given.

Expression of PAX-5 in B Cell Hodgkin and Non Hodgkin Lymphoma

Background: B-cell malignancies including Precursor B-cell lymphoblastic lymphoma/leukemia and Hodgkin Lymphoma show a wide spectrum of B-cell differentiation from early stage B-cell precursors to mature B-cells ending in terminal differentiation to plasma cells. Pan-B-cell antigens routinely used for the diagnosis of B-cell lymphoma, include CD19, CD20, CD22 and CD79a.PAX-5 protein, also known as B-cell-specific activation protein is a B-cell-specific transcription factor; essential for commitment and functional maintenance used in the diagnosis of B cell Hodgkin and non-Hodgkin lymphoma. PAX-5 show nuclear positivity in B cell lymphomas and moderate (dim) positivity in Hodgkinlymphoma Reed Sternberg cells make this marker ideal for diagnosing B cell malignances. Objective: To determine the expression of PAX-5 in B cell Hodgkin and non-Hodgkin Lymphoma in order to improve the diagnosis of B-cell lymphomas. Methods: In this Prospective study, all the cases of B cell lymphoma diagnosed at The Aga Khan University Hospital, Karachi from July 2010 to July 2011were included. A panel of Immunohistochemical stain was performed in all cases along with additional PAX- 5 stain with appropriate controls. Results: Total 125 cases were included. Hodgkin Lymphoma (Mixed cellularity) was the commonest B-cell lymphoma subtype, 32 (25%) cases. Other common subtypes included Hodgkin lymphoma (Nodular sclerosis subtype), diffuse large B-cell lymphoma and B lymphoblastic lymphoma. Conclusion: This study demonstrates that PAX-5 is the most sensitive and reliable immuhohistochemicalmarker in the diagnosis of B cell Hodgkin and non-Hodgkin lymphoma.

Lipoblastoma: a clinicopathologic review of 23 cases from a major tertiary care center plus detailed review of literature.

OBJECTIVE: Lipoblastoma is a rare neoplasm that occurs mostly in infants and children. Although benign, it has a tendency for local recurrence. RESULTS: Clinical and pathological features of 23 cases of lipoblastoma described. Patients' age ranged from 8 months to 18 years with mean and median age 4.1 and 2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4 cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed and multi nodular. All cases showed lobules composed of adipocytes and lipoblasts with intervening fibrous septa and fine vascular network. Myxoid change, capsule formation and septation were seen in all cases. Zonation was seen in 2 cases. Follow-up was available in 14 out of 23 patients. Of these, 13 were alive and free of disease with no evidence of any recurrent lesion. One patient with a mediastinal infiltrating lipoblastoma experienced 4 recurrences. Lipoblastoma is a benign adipocytic neoplasm of infants and young children. Correlation of clinical and histological features helps in reaching a correct diagnosis. Owing to a high recurrence rate following incomplete resection, a complete resection is essential. Prognosis is excellent after complete resection.

Anaplastic lymphoma kinase protein positive diffuse large B cell lymphoma; A developing world experience.

Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (ALK+DLBCL) is a rare, distinct and aggressive subtype of non-Hodgkin's lymphoma (NHL). These tumors are considered to be derived from post-germinal center B cells but peculiarly their distinction is based on the fact that they are ALK-positive neoplastic B cells but lack expression of B cell markers (CD19,CD20, CD79a), T cell markers (CD3, CD5) and CD30. Its broad differential diagnosis and similarities to plasmablastic lymphoma, immunoblastic DLBCL, Anaplastic large-cell lymphoma (ALCL) of T-null cell lineage, and poorly differentiated/anaplastic carcinoma pose a grave challenge to physicians with conventional costly treatment for DLBCL failing to yield any clinical or prognostic significance in ALK+DLBCL. In this article we present 7 cases which were reported at Aga Khan University Hospital, Department of Pathology and Laboratory Medicine from 2009 to 2015 and a review of literature on ALK+ DLBCL, which according to the best of our knowledge is the second largest reported series and the first from South Asian subcontinent.

Perception of pathology as a future career choice among medical Students from Karachi, Pakistan: Experience from a private medical school.

To determine the perception of pathology as a future career choice among medical students of a private medical school from Karachi, Pakistan. A descriptive cross-sectional study was conducted at the Aga Khan University, Karachi, Pakistan. A total of 201 students participated in this study. All Students were approached randomly to participate. A total of 201 students participant survey forms were evaluated in this study. The overall satisfaction level with pathology was observed in 61.8% of the students. Majority of the students understood subspecialties which were a part of clinical medicine. Over half of the students thought pathology as a specialty should be highlighted in a more integrated manner (59.2%) with a minority favouring a separate pathology rotation (11.9%). In conclusion, this study indicates that majority of students have a positive approach towards the field of pathology and favour incorporating it in an integrative way into the medical school curriculum.

Secretory paraspinal paraganglioma of thoracolumar spine: Case report and review of literature.

BACKGROUND: Pheochromocytomas are catecholamine secreting tumors of the adrenal medulla chromaffin cells, however, when present extra-adrenally they are called paragangliomas. Paragangliomas rarely produce catecholamine in excess, which is evident by clinical symptoms, urine, and blood biochemistry. Total resection of these tumors can lead to complete clinical and biochemical resolution. This case report presents the clinical features, radiological findings, and neurological outcome in a middle-aged female with a secretory paraganglioma. CASE DESCRIPTION: We present the case of a 34-year-old female who presented with a 2-year history of dizziness, flushing, headache, palpitations, and hypertension. Her blood workup showed raised urinary catecholamine levels. Magnetic resonance imaging (MRI) and iodine-123-meta-iodobenzylguanidine (MIBG) scans demonstrated a retroperitoneal mass located anterolateral to T11-T12 vertebral bodies reaching up to T12-L1 intervertebral disc. The patient was otherwise neurologically intact. She underwent resection of the tumor after alpha-adrenergic and beta-adrenergic blockade. En bloc resection was achieved without neurological complications. Postoperatively, the patient was initially hypotensive and subsequently became normotensive, and on follow-up, the patient had resolution of her symptoms and was stable. CONCLUSION: Secretory paraganglioma of the dorsal spine are rare and difficult to excise, needs preoperative preparation with pharmacological intervention, good operative technique, and postoperative care.

Malignant phyllodes tumor in an 11-year-old girl with fatal clinical outcome. A case report.

BACKGROUND: Phyllodes tumors are rare biphasic tumors occur predominantly in middle aged women. Malignant phyllodes tumor in children is very rare. OBJECTIVE: To report a case of malignant phyllodes tumor in a pre-menarchal girl. METHODS: H&E slides of the case were reviewed and follow up was obtained. RESULTS: The patient was 11-year-old girl who noticed a lump in her right breast 1 year back which grew rapidly in size. Wide local excision of the mass was done and histopathology revealed a malignant phyllodes tumor. Patient underwent mastectomy one month later due to recurrence. Two years later, she presented with dyspnea and chest pain. CT showed lung metastasis. The patient died of disease 1 year later due to widespread metastasis in liver and bone. CONCLUSION: We report a case of malignant phyllodes tumor in an 11-year-old girl, which behaved aggressively and patient died of disease due to widespread metastases 3 years after diagnosis.

Adenoid Cystic Carcinoma of Breast: Clinicopathologic Study of Seven Cases.

Adenoid cystic carcinoma (ACC) of the breast is a rare type of tumor. Our objective was to determine the clinicopathologic features of breast ACC. We reviewed slides of breast ACC reported during 12 years. Seven cases were identified. Age ranged from 38 to 59 years (mean = 47 years). Mean tumor size was 2.3 cm (range 1.2 to 4 cm). Histologically, dominant cribriform pattern was seen in 4 cases, solid in 2 and tubular in one case. Mitotic figures ranged from 2 to 22/10 HPFs. Grades I and II were seen in 3 cases each while 1 was grade III. Post-surgical tamoxifen given in 3 cases, chemotherapy and radiotherapy in 2 and 1 case, respectively. Follow-up ranged from 12.5 - 138.5 months (mean = 61. 25 months). One patient developed vertebral metastasis. Consistent with published data, this series indicated that ACC-breast has a good prognosis.

Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic study of 11 cases.

Mammary analogue secretory carcinoma (MASC) is a recently described tumor sharing the histologic, immunohistochemical, and molecular profile of secretory carcinoma of breast. We aimed to evaluate the morphologic and histochemical features needed/required for the diagnosis of MASC without adjunct of molecular analysis. Six retrospective cases suspicious for MASC and 5 prospective cases reported as MASC were included in the study. Molecular analysis of ETV6 by fluorescence in situ hybridization was performed at the University of Pittsburg, USA. The ages of the patients ranged from 9 to 60 years (mean, 27.5 years). Histologically, all tumors showed mixed growth patterns including microcystic, macrocystic, papillary, tubular, and solid, papillary the being most common pattern. The tumor cells showed round to oval vesicular nuclei with small nucleoli, and eosinophilic to vacuolated cytoplasm. All cases demonstrated luminal and cytoplasmic mucin on periodic acid-Schiff with and without diastase digestion and alcian blue stain. ETV6 fusion gene rearrangement by fluorescence in situ hybridization was detected in 10 of 11 tumors. Recurrences occurred in 3 patients, and 1 patient died of disease 5 years after surgery. In conclusion, MASC is a relatively rare salivary gland malignancy exhibiting distinct histologic and histochemical features which can help to differentiate it from other mimics. Histologically, papillary-cystic and microcystic patterns are the main clues to diagnosis. The follicular pattern of acinic cell carcinoma might represent MASC, as 4 cases in our series had this pattern. Two patients in our series were 9 and 9½ years old respectively, which are the youngest ages ever recorded for MASC.