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.

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.

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.

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.

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.

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.

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.

Ovarian steroid cell tumor, not otherwise specified: a clinicopathological and immunohistochemical experience of 12 cases.

AIM: Ovarian steroid cell tumors, not otherwise specified (SCT-NOS) are very rare neoplasms. No large study has been performed in Pakistan to establish the clinicopathological spectrum and immunohistochemical behavior in our region. The purpose of our study was to determine the various clinicopathological and immunohistochemical features of ovarian SCT-NOS along with follow-up in our institution. METHODS: This was a retrospective observational study. The study was conducted in the Section of Histopathology, Aga Khan University Hospital, Karachi, Pakistan. All reported cases of ovarian SCT-NOS occurring during January 1992 to August 2013 were retrieved. The slides were reviewed and patient demographics, and clinical and pathological features were noted with proforma software. SPSS version 19 was used for all analyses. Data is expressed as absolute values and percentages. RESULTS: A total of 12 SCT-NOS (2.3%) out of 528 ovarian sex cord stromal tumors were retrieved. The age range was 3-70 years, with mean of 40.75 years. The tumors ranged 2.5-13 cm in size, with a mean size of 6.1 cm. One patient had bilateral tumors. All of the tumors were positive for inhibin and calretinin. Four tumors were negative for Mic-2 (CD99). In two patients, the tumor recurred. Only one patient who had worse pathological features received adjuvant chemotherapy. CONCLUSION: Steroid cell tumors are very rare ovarian tumors in the Pakistani population, mostly presenting in adulthood. Diverse histological differentials exist so special stains and immunohistochemical stains are needed to distinguish these from other tumors.

Recurrence of adult granulosa cell tumor of the ovary: experience at a tertiary care center.

Adult granulosa cell tumor (AGCT) is the most common ovarian sex cord stromal tumor with a favorable prognosis. However, a subset of patients develop recurrence. We retrieved and reviewed 156 cases of AGCT reported between 1992 and 2012. The ages ranged from 20 to 84 years (mean, 48 years). The size of the tumor ranged from 0.8 to 25 cm (mean, 10 cm). Histologically, all tumors were composed of round or polygonal cells with indented or grooved nuclei, eosinophilic cytoplasm, and well defined cell borders. A diffuse pattern was seen in the majority followed by microfollicular, trabecular and macrofollicular. The mitotic figures ranged from 2 to a maximum of 21/10 HPFs. Focal necrosis were seen in 17 cases. Associated simple hyperplasia of endometrium was seen in 9 cases, complex hyperplasia in 2, and endometrioid adenocarcinoma of the endometrium in 3 cases. Recurrence was seen in 8 cases with a follow-up of 2 to 19 years (mean, 6 years). The recurrent tumors were mostly >5 cm and sites included the same adnexal site and contralateral ovary, omentum, mesentery of small bowel, abdominal wall, uterine and fallopian tube serosa, lymph nodes, pelvis, and appendix. Histologically, recurrent tumors exhibited a diffuse histologic pattern and a mitotic count of 6.8 as compared to 3.3 in primary tumors. In conclusion, a tumor size of >5 cm and a diffuse histologic pattern were associated with increased recurrence risk. The recurrent tumors hadz increased mitotic figures compared with primary tumors. Appendix, a very rare site of recurrence was seen in one of our cases.

Cementum-like matrix in solitary bone cysts: a unique and characteristic but yet underrecognized feature of promising diagnostic utility.

Solitary bone cysts (SBCs) are benign, intraosseus, cystic lesions, which generally involve metaphysis of long bones during the period of skeletal immaturity. Histologic features are nonspecific, but identification of amorphous cementum-like material provides a significant diagnostic clue. This material is unique to SBC with reported frequency of 10% to 70% and has been described as an immature form of bone. We retrieved and reviewed 41 cases of SBC reported in the last 10 years. The ages of patients ranged from 4 to 64 years (mean, 16 years), with a male-to-female ratio of 3:1. Humerus and femur were the most common sites. Cementum-like matrix was observed in 26 cases (63.4%). This material was seen in different phases of deposition and progression, ultimately transforming into mature bone as seen in 4 cases. Cyst wall lining was observed in 70.7% of cases along with several other nonspecific histologic features including reactive bone formation, hemosiderin macrophages, hemorrhage, multinucleated giant cells, foamy macrophages, fibrin, cholesterol clefts, and granulation tissue. Cementum-like material in the wall of SBCs is a specific and fairly consistent finding of diagnostic significance in cases where cyst wall lining is deficient. We also histologically demonstrate, for the first time, transformation of cementum-like material into reactive and mature bone, which further validates the immature osteoid nature and finding of other authors.

Non-Hodgkin's thyroid lymphoma associated with Hashimoto's thyroiditis.

We report two cases of thyroid lymphoma. First was of a 54-year-old lady who presented with a 10 year history of goiter. Examination revealed an enlarged thyroid gland extending sub-sternally, with no palpable lymph nodes. She had been on thyroxine for 4 months, due to a high TSH with positive antibodies. Fine needle aspiration cytology of thyroid showed Hashimoto thyroiditis (HT). A total thyroidectomy was done because of pressure symptoms. Histopathology revealed HT in right lobe and Diffuse Large B-cell Non-Hodgkin's lymphoma (DLBCL) in left lobe. Second case was of a 30 year-old man who presented with dyspnoea secondary to rapidly enlarging thyroid. On examination, thyroid was diffusely enlarged together with palpable lymph nodes. His TSH was elevated & Anti-TPO antibodies were positive suggesting an autoimmune etiology. Ultrasound showed, an ill-defined heterogeneous mass in the left lobe of thyroid gland with multiple enlarged lymph nodes. Ultrasound guided thyroid core biopsy revealed DLBCL.

Chondromyxoid fibroma; experience of 36 cases of an intriguing entity.

OBJECTIVE: To evaluate the clinico-pathological features and treatment options of chondromyxoid fibroma patients. METHODS: The retrospective study was conducted at the Aga Khan University Hospital (AKUH), Karachi, and comprised data of all cases of chondromyxoid fibroma of bone diagnosed between 1996 and 2013.The diagnosis had been made mostly histopathologically, but also included patients in whom preoperative incisional biopsies had been used. Histopathological and radiological findings along with various treatment options and follow-up was recorded on a proforma. RESULTS: Of the total 36 patients,14(39%) were females and 22(61%) were males, with an overall mean age ± of standard deviation 20.9 years ± 9.8 (range: 6-51 years). Diagnosis was made histopathologically in 27(75%) patients and biopsy was used in 9(25%) cases. The most common site of involvement was tibia in 16(44.4%). The main presenting symptom was pain in 30(83.3%) and/or swelling in 6(16.6%). Radiological examination revealed no foci of soft tissue involvement. Bizarre large atypical cells were seen in 14(39%) cases and osteoid formation in 2(5.5%), leading to extreme difficulty in diagnosis. Treatment options included wide resection and marginal excisionin 22(61%) cases, intra-lesional curettage in 14(39%). The mean ± standard deviation follow-up was 48.8 ± 40.2 months (range: 8-152 months). Follow-up details were available only for 19(53%) patients. Among them, recurrence occurred in 7(36.8%) patients. No functional loss developed after surgical treatment, but 3(16%) patients developed wound-site infection. CONCLUSIONS: Chondromyxoid fibroma is clinically and histopathologically rare and difficult to diagnose because of the absence of typical diagnostic features in every case.

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.

Secretory carcinoma of breast: clinicopathologic study of 8 cases.

Our aim was to describe clinicopathologic features of secretory carcinoma on a cohort of cases. We retrieved reported cases of secretory carcinoma of breast (SCB) in the Section of Histopathology, Department of Pathology & Microbiology, Aga Khan University Hospital Karachi, from May 2004 to December 2011. The slides were reviewed, and clinicopathologic features were noted. A total of 8 cases of SCB were found. The age ranged from 17 to 60 years (median, 41 years) with a female to male ratio of 7:1. Lumpectomy was done in 6 cases, and mastectomy, in 2 cases. The tumor size ranged from 2.5 to 10 cm (mean, 5.5 cm). Histologically, abundant extra- and intracellular secretory material was seen in all cases. Most of the tumors showed mixtures of patterns with dominant microcystic and papillary patterns. In situ component was seen in only 1 case. Lymph node metastases were seen in both cases with lymph node sampling. In conclusion, SCB is a rare type of ductal breast carcinoma. The papillary pattern of SCB is rare according to published data but was seen in most of our cases. In situ secretory carcinoma is even rarer, and to date, we have seen a single case only. Although most occur in women, these can be seen in men as well.

Serous carcinoma arising in endometrial polyps: clinicopathologic study of 4 cases.

Uterine serous carcinoma (USC) is a rare variant of endometrial cancer that is not related to increased estrogen level; rather, it arises in a background of atrophic endometrium. Our aim was to describe clinicopathologic features of 4 cases of USC arising in endometrial polyps (EPs). The mean age of the patients at presentation was 53 years (range, 50-61 years). All patients presented with postmenopausal bleeding. In 3 patients, endometrial curretings were done before surgery, which was reported as EP with superficial foci of USC, EP with few clusters of atypical cells, and high-grade serous carcinoma, respectively. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and omental sampling. The uterine cavity showed an EP in all cases ranging in size from 2 to 3.5 cm (mean, 3 cm). The hysterectomy specimens revealed USC in EP as well as the adjacent endometrium in 3 patients. The nonneoplastic endometrium was atrophic in all cases. Residual tumor was not found in the endometrium in 1 case. Omental metastatic deposits were found in all cases. Tumor deposits were also seen in the serosa of uterus, fallopian tubes, and parametrium in 1 case. Two patients died of disease 2 years after diagnosis. The remaining 2 patients are alive after a follow-up of 3 years, respectively. In conclusion, USC is a rare aggressive tumor, and to establish the diagnosis, it is important to look for the small foci of the tumor in the atrophic endometrium and on the surface of the polyps as these patients are likely to harbor additional disease in the uterus or extrauterine sites. The postmenopausal group is at high risk for developing these tumors; therefore, all the endometrial biopsies/curettings and the EPs in this age group should be thoroughly sampled.

Malignant vascular tumours associatedwith the breast: a study of 7 cases.

Angiosarcomas account for less than 0.05% of the malignant neoplasms of the breast. We present here 7 cases of malignant vascular neoplasms of the breast, including 2 cases of postmastectomy Stewart-Treves syndrome. In this case series, most of the patients were young. Tumour was bilateral at presentation in one case. The size of the tumours ranged from 1.6 cm to 11 cm. Although breast angiosarcomas are rare neoplasms, with the increasing use of radiation therapy for breast cancer patients, post-radiation skin lesions should not be ignored.

Invasive micropapillary carcinoma of breast: an under-recognized entity. a series of eight cases.

Invasive micropapillary carcinoma (IMPC) of breast is a morphologically distinct and relatively uncommon variant of invasive ductal carcinoma. It is characterized by small clusters of tumor cells with surrounding clear stromal spaces; a tendency for vascular permeation and therefore, an aggressive clinical course. This morphologic pattern can be easily missed especially in a small biopsy specimen because pathologists may disregard the clear spaces as artifactual. With a tendency of presenting at a higher stage, this morphological pattern needs to be mentioned in the histopathology report whenever it is encountered, either in its pure form or admixed with conventional ductal carcinoma. We describe eight cases of IMPC of breast along with their variable clinical presentations.

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.