Plasmablastic Lymphoma in a Human Immunodeficiency Virus-positive Child With a Suspicion of Concomitant Primary Immunodeficiency Disorder.

Plasmablastic lymphoma (PBL) occurs in the setting of immunodeficiency, in association with human immunodeficiency virus (HIV) infection, in elderly patients, and in the posttransplantation state. It is exceptionally rare in children. PBL is an aggressive lymphoma with a poor prognosis. We present a case of pediatric PBL in an HIV-positive child with suspicion of a concomitant underlying immune deficiency state other than HIV. A 7-year-old girl presented to the pediatric emergency department with complaints of fever and painful swelling on the left side of her face for 15 days, associated with headache, snoring, and difficulty in breathing. She had a history of watery diarrhea, oral thrush, recurrent fever, and hospitalizations for skin infections since the age of 1 year. Histopathological findings were consistent with PBL. Her HIV RNA polymerase chain reaction was positive. She was offered chemotherapy based on the FAB/LMB 96 protocol. This case demonstrates an aggressive presentation of a rare entity, HIV-associated PBL, in a child, with underlying immunodeficiency and highlights the issues which caused a significant challenge in making the diagnosis. The presence of HIV infection and contradicting other immunologic investigations posed a dilemma in establishing an association of PBL in this child. The outcome of patients with this tumor is associated with high mortality.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

Rare association of epidermoid cyst of ovary with mucinous cystadenoma- A Case Report.

Epidermoid cyst is a rare benign neoplasm of the ovary, lined by stratified squamous epithelium, lacking skin, adnexal structures, and other teratomatous elements. On the other hand, mucinous cystadenoma is one of the most common benign ovarian neoplasm that microscopically shows cystic areas lined by tall columnar mucinous epithelium. Although its coexistence with other tumours, such as mature cystic teratoma, squamous cell carcinoma, clear cell adenocarcinoma, Brenner's tumour, serous cystadenoma, etc., have been reported, a combination of benign epidermoid cyst and mucinous cystadenoma has rarely been documented in literature. We report a case of coexistence of epidermoid cyst and mucinous cystadenoma in an ovarian cyst.

Pilomatrix Carcinoma In A 4-Year-Old Child With An Unusual Presentation.

Pilomatrix carcinoma is a rare, locally aggressive variant of pilomatrixoma with a high rate of recurrence and risk of distant metastasis. We report an unusual presentation of a pilomatrix carcinoma in a 4-year-old male child who presented with recurrent lesions on his left cheek. At the age of 1 month of life, he presented with a soft tissue swelling on his left cheek. The lesion showed a circumscribed proliferation of basaloid cells with central areas of eosinophilic ghost shadow cells and intermediate cells. Basaloid nests showed round to oval, hyperchromatic nuclei with open nuclear chromatin, prominent nucleoli and frequent mitoses but no marked nuclear pleomorphism or infiltration was identified. The lesion recurred twice at the same site. Both recurrences showed similar morphology as the primary tumour however there were extensive areas of stromal necrosis, infiltrating edges, frequent mitoses with atypical forms, and lymphovascular invasion. There was no marked nuclear pleomorphism. Morphological features favoured a diagnosis of pilomatrix carcinoma. The child is still on follow-up and no recurrence has been identified to date. Pilomatric carcinoma is rarely reported in infants. Due to its rarity, aggressive histological features may be missed.

Cystic Neutrophilic Granulomatous Mastitis.

Granulomatous lobular mastitis (GLM) is an infrequent inflammatory breast disease, which can simulate malignancy on the basis of clinical and imaging features. It is typically found in parous or lactating women. The differential diagnosis of granulomatous mastitis includes infections caused by bacterial, fungal or mycobacterial agents, and autoimmune disorders like rheumatoid arthritis, sarcoidosis, giant cell vasculitis, and granulomatosis with polyangiitis. Cystic neutrophilic granulomatous mastitis (CNGM) is a sporadic sub-type of GLM that can be linked with infection with Gram-positive bacilli, specifically, Corynebacterium. It is characterised by lipogranulomas that comprise of "cystic" spaces lined by neutrophils which may contain Gram-positive rod-shaped bacteria. The majority of cases of GLM are still "idiopathic" as this pattern of inflammation still remains a mystery. We herein report three cases of CNGM and review the relevant literature. Key Words: Granulomatous mastitis, Corynebacterium, Gram-positive rods, Inflammatory breast disease, Cystic neutrophilic granulomatous mastitis.

Extramedullary hematopoiesis in an inguinal lymph node: an unusual presentation of primary myelofibrosis.

BACKGROUND: Extramedullary hematopoiesis (EMH) is a proliferation of hematopoietic tissue outside of the bone marrow medullary space. It is a pathophysiologic response, more often associated with either a benign reactive hematological disease or a myeloproliferative neoplasm (MPN). Identification of EMH in adults is always pathologic. It is highly unlikely for a myeloproliferative neoplasm to present with inguinal lymphadenopathy. An unusual and complex case can be precisely diagnosed via a multidisciplinary approach involving experts from various modalities of laboratory. In this regard, the present case highlights the importance of an integrated approach in establishing the diagnosis. CASE PRESENTATION: We report a case of a 61-year-old male patient of primary myelofibrosis who presented with extramedullary hematopoiesis in an inguinal lymph node. The patient initially presented with generalized symptoms including anemia, fatigue, abdominal pain, and weight loss. On examination, massive splenomegaly. Chest X-ray revealed consolidation which was secondary to right-sided pleural effusion. Therefore, he was suspected to have a lung carcinoma. However, lymph node biopsy revealed extensive fibrosis, consequently effacing the nodal architecture. An abnormal blood picture raised the possibility of bone marrow infiltration. Extensive panel of markers is tested on lymph node and bone trephine. Cytogenetic studies with G-banding analysis and fluorescence in situ hybridization (FISH) played a significant role in deriving clinical decision. Translocations identified in conventional cytogenetic workup led to the diagnosis of primary myelofibrosis. The case is being reported due to unusual presentation of PMF. CONCLUSION: In conclusion, it is a distinctive case of myeloproliferative disorder initially presented with extramedullary hematopoiesis and through multidisciplinary workup successfully diagnosed as primary myelofibrosis. Awareness of unique clinical presentations and integrated approach towards diagnosis is the key to such challenging cases.

Fibrolipoma of Tongue: A Rare Entity.

Lipomas are benign mesenchymal tumors that comprise almost one-half of all soft tissue tumors. Lipomas can occur at any site where fat cells are present but are rare in the oral cavity, especially the tongue, which is a very rare site. Lipoma has several variants. Fibrolipoma is a rare variant and accounts for 25-40% of lipomas of the tongue. In only 14 cases, the diagnosis of fibrolipoma has been made histologically. Most cases of lipomas occur above 40 years of age. Herein, we report a case of fibrolipoma of the tongue in a young female of 18 years. The patient presented with complaint of swelling on the dorsum of the tongue for 8 years. The swelling was surgically excised and microscopically a diagnosis of fibrolipoma was made. In conclusion, oral lipomas especially lingual lipomas are a rare entity. Although oral lipomas mostly occur above 40 years of age, they can occur at a younger age. Key Words: Fibrolipoma, Tongue, Histopathology.

Frequency, Distribution Of Subtypes And Immunohistochemical Profile Of Non-Hodgkin Lymphoma In Paediatric And Adolescent Patients.

BACKGROUND: Non-Hodgkin lymphoma is a common malignant disorder in paediatric and adolescent age group. There is a need of large-scale studies to understand the disease pattern in Pakistan as no official registry exist in most of the developing countries. This study comprised a large cohort of 223 patients, spanned over a decade from January 2008-December 2019 and aimed to report the prevalence of subtypes, demographics and immunohistochemical profile from this region. METHODS: Retrospective study, conducted at Indus hospital and health network and Ziauddin university hospital, Karachi, Pakistan. Sequential data analysis was carried out on all consecutive samples including both needle and excisional biopsies of patients below 18 years of age. Morphological examination of H&E stained sections along with immunohistochemistry is performed in order to identify subtypes and immunophenotypic patterns using an extensive panel of markers. RESULTS: Our results demonstrate 66% B-cell lymphomas while 34% T-cell lymphomas. Overall male to female ratio was 3.3:1 with median age 8 years (1.1-17 years). Among B-cell lymphoma, Burkitt lymphoma is most common while in T-cell, T-lymphoblastic lymphoma is the most common subtype. In anaplastic large cell lymphoma category, null cell phenotype was predominant, i.e., 65%. T-NHL frequency is found to be higher in our population. However, results of immunohistochemistry are similar to published literature. CONCLUSIONS: The study will help to identify disease patterns in terms of subtypes of NHL and its immunohistochemical profile that plays a vital role in diagnostic, prognostic and therapeutic implications.

Histopathological Features Of Denosumab Treated Giant Cell Tumours Of Bone "A Single Institutional Experience" At A Tertiary Care Center, Karachi.

BACKGROUND: Giant cell tumour (GCT) is a primary benign, locally aggressive bone tumour. Treatment is surgical however, denosumab has been increasingly used as a treatment in recurrent or unresectable locally advanced GCT because of its effect in reducing tumour size. Denosumab treated GCT can exhibit a wide array of histopathological features resulting in diagnostic problems for pathologists. Our study aimed at identifying these histopathological features to aid pathologists in reaching a correct diagnosis. METHODS: Our study included 20 patients of biopsy-proven GCT cases treated with denosumab. We received specimens for histopathological examination in our institution from January 2018 to March 2020. The demographic and clinical data of these patients were retrieved from the Health Management Information System (HMIS). The slides were retrieved and studied for histopathological changes. RESULTS: The mean age of patients in our study was 29.5 years. There were 11 males and 9 females. Distal radius was most commonly involved bone. On histopathological examination, ovoid to spindle mononuclear stromal cells were seen. Total absence of osteoclast like giant cells was seen in 10 (50%) cases, whereas 3 (15%) cases showed a marked reduction in osteoclast like giant cells. CONCLUSIONS: Denosumab treated GCT of bone can exhibit a wide spectrum of histopathological features. Pathologists need to be mindful of these features. Correlation of histopathological findings with clinical history and radiological features is important to prevent erroneous diagnosis. Treatment history of patients with denosumab is essential as incorrect diagnosis can be made if the history of denosumab treatment is not provided.

High risk histopathological factors in retinoblastoma in upfront enucleated eyes: An experience from a tertiary care centre of Pakistan.

Background & Objectives: The assessment of histopathological risk factors (HRFs) in retinoblastoma in upfront enucleated eyes is important in deciding treatment protocols. Limited data is available from the developing countries as very few studies were conducted on retinoblastoma. The study aims to report this data from Pakistan. Methods: This cross-sectional study included treatment naïve retinoblastoma patients who underwent upfront enucleation between 2017 to 2021. Various tumor characteristics i.e. laterality, size, histologic grade, anaplasia grade, growth pattern, extent and length of optic nerve invasion, pathologic staging, tumor involvement of ocular structures were assessed. High-risk factors such as involvement of anterior chamber, choroidal, scleral, extrascleral, and optic nerve were also noted. Results: A total number of 54 patients were enrolled, out of which 53.7% were females while remaining were males. Median age at presentation was 24 months. Unilateral tumor was seen in 92.6% cases. Most frequent histologic grade was G2 (64.7%) and moderate anaplasia was observed in 59.2% cases. Vitreous involvement was seen in (86.5%). Pathologic staging of most of the tumors was pT1 (39.2%). Assessment of high-risk factors revealed that optic nerve involvement (35.1%) was the most common finding with retrolaminar tumor invasion seen in 75% cases. Choroidal invasion (≤3mm) was seen in 55.6% of patients. Limited involvement of anterior chamber (3.8%), sclera (7.4%), and extrascleral (3.8%) tissue was also observed. Conclusion: The presence of high risk histopathological factors in enucleated eyes diagnosed with retinoblastoma are known to have a profound impact on the risk stratification as well as decision of future treatment plan.

Chemotherapy induced histopathological changes in retinoblastoma, assessment of high risk predictive factors & its correlation with comorbid conditions.

Background & Objectives: Retinoblastoma is a malignant intraocular tumor and its treatment requires a multidisciplinary approach. Chemotherapy is an important modality in treatment of retinoblastoma. The purpose of this study was to assess the histopathological changes in retinoblastomas treated with chemotherapy along with correlation of comorbid conditions with high risk histopathological factors (HRF). Methods: All post-chemotherapy enucleated eye specimens received in the pathology department between 2017 to 2021 were included in the study. Slides were retrieved and reviewed for chemotherapeutic effects, tumor regression, and for assessment of HRF. Patient demographic data, information regarding chemotherapy and co-morbid conditions were retrieved through the hospital database. Chi-square was used to analyze the relation between comorbid conditions and HRF. Results: Chemotherapeutic effects were seen in all eyes with varying degrees of responses. Necrosis, calcification, and gliosis were the most common findings. The majority of eyes showed tumor occupying less than 50% of the eye whereas complete regression was noted in one eye only. Retinal detachment, glaucoma, and buphthalmos were the most common comorbid conditions at the time of diagnosis. Patients with glaucoma were more likely to have ciliary body invasion. Kaplan Meier analysis showed that patients with more than two HRF had decreased survival rates in comparison to those with one or no HRF. Conclusion: Histopathological evaluation of chemotherapy-treated eyes shows varying degrees of response to chemotherapy. Post enucleation histopathological evaluation of the globe plays an important role in assessing disease activity and guiding further treatment to prevent metastasis.

Correlation of clinical and radiological predictors of retinoblastoma with high-risk histopathological features.

INTRODUCTION: Retinoblastoma (RB) tumors having high-risk histopathologic features (HRFs) have an increased risk of metastasis and disease relapse. However, RB has not been studied widely in Pakistan. Therefore, we evaluated the association of clinical, histopathologic, and radiological findings with HRFs in patients with RB who were treated at the Indus Health & Hospital Network in Karachi, Pakistan. METHODS: We enrolled treatment-naïve patients with RB who received upfront enucleation from September 2017 to February 2021. We evaluated enucleated eyes with the Intraocular Classification of Retinoblastoma system and classified HRFs as invasion of the anterior chamber, including the iris and ciliary body, or massive invasion of the choroid, sclera, or optic nerve (postlaminar and/or up to the transection line). RESULTS: Of 117 patients with RB treated at our institution during the study period, 54 received upfront enucleation. Unilateral disease was present in 92.6% of cases. The most frequent disease signs and symptoms included the presence of vitreous seeds (30.6%) and leukocoria (100%), respectively. The most frequent HRFs and radiological findings comprised massive choroidal invasion (15.1%) and anterior chamber enhancement (66.7%), respectively. The majority (62.9%) of patients did not exhibit any HRFs. Female sex, pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma had significant predictive ability for HRF occurrence. CONCLUSION: Pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma are important clinical factors that should be taken into consideration before the management of RB. Early recognition of high-risk histopathological and radiological features is essential for appropriate treatment of RB.

Myoepithelial Carcinoma arising in a background of pleomorphic adenoma.

Carcinoma ex pleomorphic adenoma is a neoplasm of the salivary gland that causes 3.6% of salivary gland tumours and 12% of salivary gland malignancies. It is a myoepithelial or epithelial neoplasm that arises from pleomorphic adenoma, whether primary or recurrent. Historically carcinoma ex pleomorphic adenoma is considered a high-grade malignancy. Salivary duct carcinoma and high-grade adenocarcinoma are the histologic types that most commonly arise in the background of Pleomorphic adenoma. However, 15% of tumours arising in Pleomorphic adenoma are considered low grade and have sluggish growth. Low-grade carcinoma ex pleomorphic adenoma can be difficult to differentiate from cellular pleomorphic adenoma. The case of a 56-year-old female patient who had neck swelling is being presented. The biopsy showed spindle cell component with mild atypia, invasion into surrounding tissue, and increased mitotic activity on the basis of which a diagnosis of Low-grade carcinoma ex pleomorphic adenoma developing in a background of pleomorphic adenoma was made. The morphological and immunohistochemical features confirmed the carcinoma component to be myoepithelial.

Cytological features of a complete hydatidiform mole in a cervicovaginal smear: A case report.

Exfoliated trophoblastic cells can be seen in a cervicovaginal smear in cases of normal pregnancy or gestational trophoblastic disease (GTD) and can mimic high-grade squamous intraepithelial lesion (HSIL) or malignancy. Although they appear highly anaplastic, cytological features such as high nuclear to cytoplasmic ratio, irregular nuclear contours and scanty basophilic cytoplasm admixed with cytologically benign squamoid and endocervical cells can aid in differentiating them from malignant cells. We present a case of a 37-year-old woman with abnormal uterine bleeding for 3-months. There was no history of recent pregnancy or previous GTD. Her cervicovaginal smear showed a hypercellular smear exhibiting cytologically benign superficial and intermediate squamous cells along with clusters of benign endocervical cells with interspersed mononucleate cells. These mononucleate cells were large, with a hyperchromatic, pleomorphic nuclei, and scant basophilic cytoplasm. Cytological features were suggestive of trophoblastic cells and workup for pregnancy and GTD was advised. Her laboratory investigations showed markedly raised levels of ß human chorionic gonadotropins (ß-HCG) and ultrasound showed a uterine mass with snowstorm appearance. A uterine evacuation was performed after which histopathological examination showed microscopic features consistent with a complete hydatidiform mole. The rare presence of trophoblastic cells in a cervicovaginal smear can easily be confused with malignant cells and can be misleading to the pathologist. Trophoblastic cells should always be kept in mind when evaluating a cytology smear of a young patient irrespective of gestational status.

Burkitt Lymphoma With Aberrant Immunophenotype Imposing Diagnostic Challenge.

BACKGROUND: Burkitt lymphoma (BL) exhibits a characteristic immunophenotype that is positive for pan-B-cell antigens and germinal center markers while negative for immature markers. A deviation from classic immunophenotype can cause diagnostic confusion and might result in false exclusion of BL. In some cases, overlapping clinical, morphological and immunophenotypic features of BL and B lymphoblastic lymphoma (B-LL) can be of diagnostic challenge. However, definitive delineation is of paramount importance due to difference in treatment. We describe a case of BL in a child with atypical features including absence of L3 morphology in diagnostic tissue and aberrant expression of CD34, CD99 and BCL2 on immunohistochemistry. These findings led to the interpretation of B-LL which was later on excluded by detection of t (8;14). This unorthodox case not only highlights the importance of cytogenetic testing but also emphasizes the correlation of all the diagnostic tools before making a definitive diagnosis. Therefore, reporting this case will help in eliciting the high index of suspicion among pathologists for this exceptionally unusual immunophenotype.

Abdominal actinomycosis in an elderly diabetic.

Actinomycosis is a rare infectious disease that presents as three entities, cervico-facial, abdominal and genital, with cervico-facial being the commonest. Due to its subacute presentation and indolent course, abdominal actinomycosis is difficult to diagnose and is often confused with malignancy. We present a case of an elderly diabetic with no known other risk factors of the disease with complaints of right sided abdominal swelling and presence of abdominal mass on imaging, diagnosed post operatively as a case of abdominal actinomycosis, on histopathology. Abdominal actinomycosis should be considered in differentials in cases with abdominal masses. Diabetes Mellitus is not an established risk factor for development of abdominal actinomycosis. Studies are required to link its association with the disease.

Ovarian angiosarcoma: a case report and review of the literature.

INTRODUCTION: Sarcomas of the ovary can either be histologically pure or can represent components of a more complex tumor. Ovarian angiosarcomas are rare, and probably arise from carcinosarcomas, teratomas or the rich ovarian vasculature. To date, only two small case series have been published, one with four cases and the other with seven. CASE PRESENTATION: A 41-year-old Saudi woman presented to our gynecological clinic with abnormal vaginal bleeding. The initial clinical diagnosis was left ovarian cyst. The results of the remainder of her abdominopelvic examination were normal. Peri-operatively, the left ovarian mass resembled a hemorrhagic solid tumor. It was sent for frozen sectioning, which revealed it was an undifferentiated neoplasm. The final histopathological examination showed a vascular neoplasm showing vasoformative arborizing channels of variable sizes and shapes lined by atypical endothelial cells with intact capsule. Areas of necrosis were seen, along with fused anastomosing solid vascular area. She was diagnosed as having an angiosarcoma of intermediate grade, International Federation of Gynecology and Obstetrics stage IA. CONCLUSIONS: Patients with ovarian angiosarcomas most commonly present with abdominal pain, however some patients present with distant metastases, often in the lungs. Spread beyond the ovary is present at the time of diagnosis in most reported cases, with disease progression within less than a year after diagnosis. Cases of advanced stage disease behave aggressively and demonstrate poor response to surgery and chemotherapy, with an overall poor prognosis. They have a tendency for local recurrence and metastases, and prognosis is hence poor; the reported five-year survival rate is 10 percent to 35 percent, however, cases confined to the ovary have survived up to nine years.