Search

Hepatocellular carcinoma (HCC) is the most common primary liver malignant neoplasm. Multiple risk factors have been identified for several decades for this overly aggressive tumor. HCC is an overly aggressive malignancy with frequent intrahepatic and extrahepatic metastasis. In our practice, we have observed that HCC has the propensity to metastasize to very unusual sites and can sometimes show variable patterns leading to diagnostic difficulty. In this study of 257 patients, we aim to discuss the unusual sites of HCC metastasis, the various patterns of metastasis, clinicopathological features, and the most common cause of HCC in our population. In the course of our research study, we systematically extracted a comprehensive dataset comprising 257 instances of metastatic HCCs from the hospital database spanning the period from 2016 to February 2022. The assessment of metastatic sites uncovered a wide range of locations, reflecting significant diversity. The most common location was bone, with 135 cases (52.5%). The vertebral column was the most common location among bony metastasis, with 63 cases (24.7%). Morphologically, the most common histological pattern observed was pure trabecular in 192 patients (74.7%). All cases were diagnosed with the help of immunohistochemical stains. Out of 257 cases, 29.18% were diagnosed using glypican-3 and HepPar1, while 26.1% relied solely on HepPar1 positivity. HepPar1 was performed in a total of 240 cases, and positivity was seen in 205 cases (85.5%). In summary, our study represents the most comprehensive investigation of clinicopathological characteristics in metastatic HCC conducted within the past 20 years. It helps understand the histological and immunohistochemical features useful for diagnosis at metastatic sites for tumors with an unknown primary., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Institutional Review Board (IRB) of Shaukat Khanum Memorial Cancer Hospital and Research Centre issued approval EX-07-02-22-01. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Zamil et al.)

Background Round cell sarcomas pose diagnostic challenges due to overlapping histopathological features, necessitating precise immunohistochemical markers for accurate categorization. NKX2.2 has emerged as a sensitive diagnostic tool, particularly in Ewing sarcoma. This study extends this understanding to various round-cell sarcomas, shedding light on the potential diagnostic utility of NKX2.2 beyond its established role. The nuanced exploration of NKX2.2 expression aims to enhance diagnostic strategies, prognostic assessments, and therapeutic developments in the landscape of sarcoma research. Methodology Cases were retrieved from the surgical pathology and consultation files of Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. Representative hematoxylin and eosin-stained slides of six different types of already confirmed tumors, including lymphoblastic lymphoma, neuroblastoma, rhabdomyosarcoma, synovial sarcoma, Wilms tumor, and Ewing sarcoma, were reviewed by a panel of pathologists. Immunohistochemistry, utilizing a rabbit anti-NKX2.2 monoclonal antibody, was performed on formalin-fixed paraffin-embedded tissue sections. The presence of NKX2.2 was defined as moderate or high nuclear immunoreactivity in at least 5% of cells. Results The histopathological examination revealed characteristic features in each sarcoma subtype, aligning with established diagnostic criteria. In Lymphoblastic lymphoma, T-cell lineage was confirmed through TdT expression, while the atypical finding of focal NKX 2.2 expression hinted at genetic diversity. Neuroblastoma exhibited the expected salt and pepper chromatin pattern, with NKX 2.2 expression raising questions about its prognostic significance. Rhabdomyosarcoma presented primitive cells expressing desmin, and NKX 2.2 focal expression echoed previous subtype-associated studies. Synovial sarcoma displayed both monophasic and biphasic growth patterns and TLE1 expression, with NKX 2.2 variation suggesting tumor heterogeneity. In Wilms tumor, the characteristic WT1 expression was observed, while NKX2.2's absence reaffirmed its irrelevance in this context. Ewing sarcoma displayed the anticipated homogenous cell population, strong NKX2.2 expression, and CD99 positivity across various sites. Furthermore, age and gender impact on this range of sarcomas found no significant relation with an expression of NKX2.2. Conclusion In conclusion, the diverse expression profiles of diagnostic markers discovered in this study, particularly the atypical expression of NKX2.2 beyond its established role in Ewing sarcoma, signify a significant advancement. This unique finding accentuates the potential diagnostic importance of NKX2.2 in various sarcomas, presenting a novel dimension to our understanding of these malignancies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Saeed et al.)

Background Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are two rare but aggressive soft tissue sarcomas that can be difficult to distinguish due to histopathological similarities. The present study examines the diagnostic capacities of mucin-4 (MUC4), a transmembrane mucin, in identifying different types of sarcomas and broadens its evaluation to include a wide range of sarcomas. Methods Immunohistochemical (IHC) examination of tissue samples from various sarcomas was performed using a mouse anti-MUC4 monoclonal antibody. IHC was conducted on 4-mm thick formalin-fixed paraffin-embedded tissue sections after pressure cooker antigen retrieval with a mouse anti-MUC4 monoclonal antibody. Results MUC4 was shown to be highly expressed in SEF (n=13) and LGFMS (n=10), while focal positivity in synovial sarcoma (n=1). Other sarcomas, such as malignant peripheral nerve sheath tumors, fibrosarcoma, leiomyosarcoma, liposarcoma, and myxofibrosarcoma, exhibited no expression (n=0). These findings are consistent with previous research and support MUC4 specificity as a SEF and LGFMS marker. This study provides information on the diagnostic efficacy of MUC4, particularly in the context of certain subtypes. It not only helps our understanding of these unique instances, but it also provides context for histopathological and IHC findings in soft tissue sarcoma. Furthermore, this study investigates the influence of age and gender on MUC4 expression in a range of sarcomas, which was typically understudied in the literature and found no relation with expression of MUC4. Conclusion In conclusion, this study adds to our understanding of soft tissue sarcomas by emphasizing the crucial role of MUC4 in certain sarcoma subtypes while acknowledging the complex variety of the sarcoma landscape. Further research is needed to understand the molecular mechanism that governs marker expression patterns, as well as the therapeutic implications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hassan et al.)

Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The non-invasive form includes fungal ball and allergic FRS, and invasive form includes acute invasive FRS, chronic invasive FRS, and granulomatous FRS. Invasive fungal infections are associated with high morbidity and mortality, hence requiring urgent medical and surgical intervention. The histomorphology can help identify certain fungal organisms that cannot be cultured or are rarely visible in exudates. The morphologic diagnosis of tissue invasive and non-invasive fungal infection is essential for appropriate treatment. We analyzed cases of rhinosinusitis from 2017 to 2019 in Pathology Department at a tertiary care cancer hospital, Lahore, Pakistan. All clinical information was retrieved from patient records. Paraffin-embedded tissue blocks were stained with hematoxylin and eosin (H&E), special Grocott methenamine silver stain (GMS), and periodic acid Schiff stain (PAS) according to standard protocol. They were reviewed by two pathologists blinded by fungus status. A total of 169 cases of rhinosinusitis were reviewed. FRS comprised 146 (86.4%) of them. The mean age of patients with FRS was 32.8±14 years. The male:female ratio was 1.4:1. Maxillary sinus was the main site of involvement in 39 (27%) FRS cases. Aspergillus was identified in 117 (80.1%) cases of FRS. The culture reports were available in 44/146 (30.14%) FRS cases. They were negative in 22/44 (50.0%), and Aspergillus species were isolated in 18/44 (40.9%) cases of FRS. There were 84 (57.5%) cases of non-invasive FRS and 59 (40.4%) cases of invasive FRS. Among invasive FRS, there were 56 (38.4%) chronic granulomatous FRS cases including mixed patterns. Majority cases, 54 (96.4%), of chronic granulomatous FRS showed a unique crowded giant cell pattern comprising of foreign body and Langhans type giant cells. These giant cells were arranged closely forming irregular non-caseating granulomas surrounded by lymphocytes and fibrosis. Interestingly, the giant cells were scattered haphazardly without forming a granuloma as well. Fungal organisms were identified in all 56 cases of chronic granulomatous FRS. Histologically, predominant organism was Aspergillus in 48 (85.7%) on GMS and PAS stain. Our study observed a unique crowded giant cell pattern, which is a hallmark of invasive fungal infection. If pathologists are familiar with this unique pattern, they can make a quick and accurate diagnosis on histology. The physician can start antifungal treatment timely for better prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Maruf et al.)

Gemistocytic differentiation is a rare histological feature seen in IDH mutant Astrocytomas. The 2021 World Health Organization (WHO) retains the diagnosis of IDH mutant Astrocytoma with its classical histology and tumors with the rare histological pattern of g emistocytic  differentiation.  Gemistocytic  differentiation has historically been associated with a worse prognosis and shorter survival, and this prognostic difference has not been investigated in detail in our population. A population-based retrospective study included 56 patients with IDH mutant Astrocytoma with Gemistocytic differentiation and IDH mutant Astrocytoma diagnosed between 2010 and 2018 in our hospital. Demographic, histopathological, and clinical parameters were compared between the two groups. Gemistocyte percentage, perivascular lymphoid infiltrates, and Ki-67 proliferation index were also analyzed. A Kaplan-Meier analysis was done to analyze any prognostic difference in the overall survival time between the two groups. Patients with an IDH mutant Astrocytoma having g emistocytic  differentiation had an average survival period of 2 years, while patients diagnosed with an IDH mutant Astrocytoma had an average survival time of approximately 6 years. There was a statistically significant decrease in survival time (p = 0.005) for patients with tumors with g emistocytic  differentiation. The percentage of gemistocytes and the presence of perivascular lymphoid aggregates did not correlate with survival time (p = 0.303 and 0.602, respectively). Tumors with g emistocytic  morphology had a higher mean Ki-67 proliferation index (4.4%) than IDH mutant Astrocytoma (2.0%, p = 0.005). Our data suggest that IDH mutant Astrocytoma with Gemistocytic differentiation is an aggressive variant of IDH mutant Astrocytoma associated with a shorter survival time and an overall worse prognosis. This data might be helpful to clinicians in the future management of IDH mutant Astrocytoma with Gesmistocytic differentiation as an aggressive tumor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hassan et al.)

Background Malignant melanoma is a common cancer in Scandanavian countries due to increased exposure to ultraviolet light. Very limited data is available on malignant melanomas in Pakistani population and further studies are needed to determine its incidence in our population. Objective The main objective of our study was to determine histopathological characteristics and prognosis of malignant foot melanomas in Pakistani patients. Material and methods After approval by the Institutional Review Board, we performed a retrospective study of 59 consecutive cases of malignant acral melanoma from the year 2016-2019. The follow-up of in-house cases was available in hospital archives. The follow-up of diagnostic patients was done through direct communication. The histological features were assessed, and the prognosis was determined in terms of recurrence, metastasis, and death. Results The main histological features assessed were Breslow thickness <1 (n=3), >1-2 (n=9), >2-4 (n=12), >4 (n=36), ulceration was present in 65% (n=39), and pathological stage 1 (n=3), stage 2 (n=9), stage 3 (n=12) and stage 4 (n=36). The margin was involved in 28.3% (n=17) cases. Recurrence was observed in 47.4% (n=28), metastasis in 55.9 % (n=33), and death was observed in 49.1% (n=29). The mean follow-up duration of 3.4 years ± 0.20 (Range 3 to 6 years). The recurrence-free survival was 2.9 ± 0.24 years, metastasis-free survival was 2.8 ± 0.237 years, and disease-specific survival was 3.4 ± 0.203 years.  Conclusion Malignant acral melanoma is fatal with high mortality rates. In our part of the world, acral melanoma has poor prognosis compared to non-acral melanomas. When compared with acral melanomas in other parts of the world prognosis is even worst. Early diagnosis and treatment are crucial in terms of patient management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shahid et al.)

Background Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of uncertain differentiation, which has various clinical and morphological presentations. Although it behaves in a benign manner, it has malignant potential. Aim To share various histological patterns and survival data in our population of this rare entity. Materials and methods We studied 25 patients who reported AFH from January 2011 to December 2021. Clinical information, gross and histological features, immunohistochemical results, and survival data were compiled and analyzed. Results Among 25 cases reported as AFH, the majority (68%) were males with a mean age of 31.8 years at the time of diagnosis. The most common location was the lower extremity, especially the thigh (56%), and the mean size of the lesion was 55 mm. Most of the lesions were superficial (84%). Grossly, the majority of lesions (76%) had a solid appearance. Microscopically, classic spindle cell morphology was the most common (76%) with a lymphoid cuff and intralesional hemorrhage. Mild cellular atypia was seen in most (92%) of the cases, while some biopsies (8%) had a high-grade morphology. The majority of patients were alive, while one patient died of the disease. Conclusion AFH is an under-recognized entity with various clinical and histological presentations and a low malignant potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Maqbool et al.)

Introduction: Fibroadenomas (FAs) and phyllodes tumors (PTs) are less prevalent but allied to have malignant transformation in many instances. It is a challenge to diagnose the phyllodes by conventional trucut biopsy technique., Objective: To evaluate the histological characteristics of tumors labeled as fibroepithelial lesions of breast tissues on trucut biopsy and compare with a diagnosis on excision biopsy., Methods and Materials: It was a descriptive cross-sectional study that was carried out in Shaukat Khanum Memorial Hospital and Research Centre within six years from January 2015 to January 2021. In trucut samples, stromal cellularity, stromal cell nuclear atypia, mitotic count, stromal overgrowth, the enhancement of stromal cellularity adjacent to epithelium were scrutinized. In each category, the activity was seen as absent, mild, moderate, or severe. Mitotic activity was graded as 0-1, 0-5, 5-10, >10., Results: A total of 125 patients were registered for the study. The mean age of patients in our study was 33.86 ± 9.95 years. The mean size was 41.02 ± 27.38 mm with a mean lump duration of 7.52 ± 5.34 months. In the FA group, the trucut sampling report showed the stromal cellularity as mild in 62 (69.7%) and stromal cell nuclear atypia as absent in 68 (76.4%) cases. But in the phyllodes tumor group, the stromal cellularity was severe in 10 (27.8%) patients and stromal cell nuclear atypia was severe in five (13.9%). The ultimate outcome showed that 89 (71.2%) patients had FA and 36 (28.8%) had PT at excision., Conclusion: Assessment of tumor size, stromal cellularity, mitoses, and enhancement of stromal cellularity adjacent to epithelium are useful markers for diagnosing the PT in trucut needle biopsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Latif et al.)

Background Diffuse midline gliomas with the H3K27M mutation are now recognized as separate entities due to their unique molecular signature, clinical features, and adverse outcome. Objective To determine the morphological spectrum and survival rate of diffuse midline gliomas with H3K27M mutation. Material and methods This retrospective study was conducted between January 2015 and January 2021 at Shaukat Khanum Memorial Cancer Hospital and Research Centre. Medical records of 28 cases of H3K27M-mutated midline gliomas were retrieved. Case slides were reviewed and the pertinent histological spectrum was evaluated. Results The mean age of patients was 24.36 ± 14.06 years. There were 21 (75%) males and 7 (25%) females. Biopsy was performed in 22 (78.6%), total resection in 1 (3.6%) while subtotal resection was done in 5 (17.9%) cases. Histologically, a spectrum of morphologies was noted with pilocytic astrocytoma (WHO grade 1) at one end and glioblastoma (WHO grade IV) at the other end. Immunohistochemically, all 28 cases were positive for Histone 3 immunohistochemistry. ATRX was performed in 7 (25.0%) cases with loss of ATRX expression in 3 (10.7%) and retained expression in 4 (14.3%) cases. Ki67 was <5% in 6 (21.4%), 5-10% in 1 (3.6%), 11-15% in 1 (3.6%), 16-20% in 3 (10.7%), 21-25% in 4 (14.3%), and 26-30% in 2 (7.1%) cases. The mean survival was 8.00 ± 9.39 months. Out of 28 patients, 15 (62.5%) patients died of disease. Conclusion Diffuse midline gliomas with H3K27M mutation is an aggressive entity with a broad morphological spectrum., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Hassan et al.)

Adrenocortical carcinoma (ACC) is a rare and highly aggressive tumor with a poor prognosis. The literature on prognosis from low-income or low-middle-income countries is limited and scarce. This study aimed to determine the clinical and histopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and the factors affecting ACC's prognosis. This was a retrospective study of patients that presented with ACC to the Shaukat Khanum Memorial Cancer & Research Center, Lahore, Pakistan, between January 2011 and May 2018. Information regarding demographics and clinical and histopathological variables were extracted and analyzed. Of the 25 subjects, 16 (64%) were female. The median age of the sample was 35 years (range; 21 - 72 years). Statistically significant associations were found between RFS and functional status of the tumor (p = 0.014), cortisol overproduction (p = 0.02), androgen excess (testosterone [p = 0.03] and dehydroepiandrosterone sulfate [DHEA SO4] [p = 0.004]), Ki-67 score (p = 0.03), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.01), and composite variable of disease (p = 0.004). The OS was found to have statistical associations with cortisol hypersecretion (p = 0.02), DHEA SO4 excess (p = 0.01), Modified Weis Score (p < 0.001), mitotic rate (p = 0.02), stratified mitotic rate (p = 0.003), and composite variable of disease (p = 0.001). Linear regression (forward-type) analysis suggested that the functional status of the tumor and the disease recurrence index statistically predicted the variance in RFS and OS, respectively. Multiple clinical and histopathological variables appear to affect the prognosis of ACC. However, based on multivariable analysis, it appears that the functional status of the tumor and the composite variable of disease recurrence are predictors of RFS and OS, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sohail et al.)

Introduction Breast phyllodes tumor's (PT) clinical behavior is difficult to predict on histology. There is limited amount of data available on the role of biological markers. The objective of this study was to assess the expression of CD117 (c-KIT) in PT of the breast and its relationship with morphology and clinical outcome. Methods A total of 78 patients having available clinical records between 2004 and 2014 with breast PT were retrieved from the cancer registry at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore and were followed up. Immunohistochemical studies were performed on all the cases using mono-clonal antibody CD117 (DAKO A4502) using Leica Bond-Max automated biosystem (Leica Biosystems, Melbourne, Australia). Staining proportion and intensity of both epithelial and stromal elements were analyzed. Evaluation of the protein expression was determined and scored. Results Patients' mean age was 45.13 ± 11.4 years. Thirty-nine (50.0%) patients had tumor on right side, 38 (48.7%) had on left and only one (1.3%) was bilateral. Thirty-two (41.0%) patients had benign PT, 21 (26.9%) had borderline and 25 (32.1%) had malignant PT. Negative CD117 expression was observed in 20 (62.5%), eight (38.0%) and 12 (48.0%) of benign, borderline and malignant PTs, respectively. Positive CD117 expression was observed in 12 (37.5%) benign, 13 (61.9%) borderline and 13 (52.0%) malignant PTs. There was insignificant association between CD117 expression with respect to tumor sub-type, patient's age and clinical behavior (p-value > 0.05). Conclusion CD117 expression was not found to be associated with tumor type and was not associated with increased risk of recurrence in this sample of patients. Further work is needed to better understand the prognostic value of CD117 expression in breast PTs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Jahangir et al.)

Background and objective Müllerian adenosarcomas (MA) are rare biphasic tumors with benign epithelial and sarcomatous stromal components. There is very limited cohort study data on MA in the South Asian countries and no such study has been attempted in Pakistan. Our aim was to evaluate the clinicopathological characteristics of MA and to review the published literature on the condition. Additionally, we also analyzed the impact of various prognostic factors on the overall survival (OS) of patients with MA. Materials and methods This was a retrospective observational study performed at the Shaukat Khanum Memorial Hospital and Research Centre, Lahore from 2003 to 2020. A total of 59 histologically confirmed cases of MA were included in the study and critically reviewed. Results The mean age of the patients was 54 ±16 years, and the most common tumor location was the uterine corpus (48, 81.4%), followed by the cervix (eight, 13.6%), ovary (two, 3.4%), and vagina (one, 1.7%). Sarcomatous overgrowth (SO) was seen in 22 (37.3%) patients, and high-grade cytology was observed in 18 (30.5%) patients. Furthermore, lymphovascular invasion (LVI) was present in six (10.2%) patients, and myometrial invasion was noted in 25 (42.4%) patients. The follow-up details of 29 patients were available, and death was recorded in 13 (44.8%) patients with a median OS of three years. Conclusion MA is a rare and diagnostically challenging entity due to its wide differential diagnosis. It is essential to take note of different morphological features such as SO, cytological features, LVI, and heterologous differentiation because of their significant prognostic impact., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Rana et al.)

Introduction: Melanoma ranks 19th among malignancies overall and second among cutaneous types. The incidence worldwide has been on the rise over the last seven decades. Various prognostic factors have been assessed and found to have a profound impact on patient outcome. However, no such studies have been attempted in our population. Our study aimed to have an insight into the behavior of malignant melanoma in our population., Materials and Methods: Cases of cutaneous malignant melanoma treated and followed up at our institute were included in this study. Cases of mucosal and choroidal melanoma were excluded. The parameters noted were age, gender, tumor thickness, Clark level, and presence of ulceration. These parameters were individually correlated with development of distant metastasis, two-year survival, survival duration, and primary tumor and lymph node stage. Appropriate statistical analyses were done., Results: Thirty patients of cutaneous malignant melanomas were treated and followed up at our institution. There was male predilection of 1:1.5. Mean age at diagnosis was 50.1 years. Two-year survival was significantly better in females. Sun-exposed areas of the skin were most commonly involved followed by anal canal that has an unusually high incidence in our society. Majority of our cases were pT4(25) on tumor, nodal status, metastasis (TNM) staging at time of diagnosis. Increasing tumor thickness in terms of primary tumor staging was not found to have any significant impact on two-year survival, distant metastasis, lymph node stage, or survival duration. Sixty percent of cases had ulceration. There was no statistically significant effect on two-year survival (78% in ulcerated group vs 75% in nonulcerated group) and distant metastasis (61% vs 58.3%). In terms of Clark level, 20 cases were level V, seven cases were level IV, two were level III, and one was level I. There was no statistically significant difference between the Clark levels in terms of two years survival, development of distant metastasis, and lymph node stages., Conclusion: Melanoma is an aggressive malignancy that causes high morbidity and morality. It commonly presents at an advanced stage at time of diagnosis in our population. Broader studies are required with early-stage melanomas to compare the various prognostic factors and their impact on prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Atique et al.)