Case of embryonal tumor multilayered rosettes in a patient with neurofibromatosis type 1.

BACKGROUND: ETMR is a unique and highly malignant brain tumor mostly occurring in infants. This report provides a comprehensive overview of the clinical presentation, histological aspects, radiological features, and therapeutic options of ETMR. Being the first report on the co-occurrence of NF1 with ETMR, it highlight the challenges of managing a patient with complex medical conditions. CASE REPORT: We present a case of a 3 and 1/2-year-old girl with neurofibromatosis type 1 (NF1), later diagnosed with a supratentorial brain tumor reported as an embryonal tumor with multilayered rosettes (ETMR), along with possible co-occurrence of constitutional mismatch repair deficiency (CMMRD) on immunohistochemistry (IHC); however, germline testing was not performed. Even though NF1 can be associated with tumors such as gliomas, the literature has no previous case reports of ETMR coexisting with NF1. CONCLUSION: Exploring the link between NF1 and ETMR with CMMRD is crucial to improving and establishing more treatment protocols. Therefore, reporting each case's unique features would be essential in developing appropriate treatment protocols.

Paediatric choroid plexus carcinoma: a retrospective case series from Karachi.

The objective of this study is to report clinical, radiological, and histopathological characteristics of three paediatric patients diagnosed as Choroid plexus carcinoma seen at our hospital, between 2015 and 2020. Three patients were diagnosed with choroid plexus carcinomas between 2015 and 2018. The mean age at diagnosis was 1.3 years (range 8 months to 1.5 years). All the three patients had subtotal resection and received adjuvant chemotherapy. One patient also received adjuvant radiotherapy. Despite these treatment measures, residual disease was noted in all three patients and two patients were subsequently treated on palliative care grounds. The average duration of follow-up after the first surgery for all three patients was approximately 33 months. Attaining satisfactory outcome in patients with CPC is challenging. Our case series reflects the difficulty in achieving gross total resection and ensuring that the disease does not recur.

Pakistan National Guidelines for Pediatric High-Grade Gliomas.

Pediatric high-grade glioma (pHGG) is highly malignant central nervous system tumor and constitute 10% of the pediatric gliomas. Effective treatment needs a functioning multi-disciplinary team including pediatric neuro oncologist, neurosurgeon, neuroradiologist, neuropathologist and radiation oncologist. Despite surgical resection, radiotherapy and chemotherapy, most HGG will recur resulting in early death. A significant proportion of HGG occurs in context of cancer predisposition syndromes like Constitutional Mismatch Repair Deficiency (CMMRD) also known as Biallelic Mismatch Repair Deficiency (bMMRD) characterized by high mutational burden. The incidence of HGG with CMMRD is one per million patients. bMMRD is caused by homozygous germline mutations in one of the four Mis Match Repair (MMR) genes (PMS2, MLH1, MSH2, and MSH6). The use of TMZ is now avoided in CMMRD related HGG due to its limited response and known ability to increase the accumulation of somatic mutations in these patients, increasing the risk of secondary tumors. HGG should be managed under the care of multidisciplinary team to receive optimum treatment. This is particularly important for low middle-income countries (LMIC) with limited resources like Pakistan.

Building the ecosystem for pediatric neuro-oncology care in Pakistan: Results of a 7-year long twinning program between Canada and Pakistan.

BACKGROUND: Low- and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries. Collaboration between institutions in low- and middle-income countries and high-income countries is one of the ways to improve cancer outcomes. METHODS: Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article. RESULTS: A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan. CONCLUSIONS: Multidisciplinary and collaborative efforts by experts from across the world have aided in the correct diagnosis and treatment of children with brain tumors and helped establish local treatment protocols. This experience may be a model for other low- and middle-income countries that are planning on creating similar programs.

Paraganglioma of common bile duct: A case report.

Paragangliomas are rare tumours derived from the neural crest cells. Most common site for these tumours is the adrenal medulla, where they are called as pheochromocytomas. Biliary system is an extremely uncommon site for extra-adrenal paraganglioma. We report the case of a 55 year old female who presented with one-month history of jaundice and right upper quadrant discomfort. Imaging showed a well-defined rounded mass at porta hepatis with arterial enhancement causing compression over the proximal common bile duct, resulting in moderate intrahepatic biliary dilatation. The patient underwent radical excision of common bile duct and roux-en-y hepaticojejunostomy. Final histopathology confirmed paraganglioma. Approximately 10% of patients may present with extra-adrenal disease, but biliary paraganglioma are extremely rare. Only few cases have been reported in literature and the management usually involves the surgical excision. Being a rare disease, a high index of suspicion is important for diagnosis of paraganglioma at such an uncommon location.

Lung Findings in Minimally Invasive Tissue Sampling (MITS) Examinations of Fetal and Preterm Neonatal Deaths: A Report From the PURPOSe Study.

BACKGROUND: Complete diagnostic autopsy (CDA) is considered to be the gold-standard procedure that aids in determination of cause of death in stillbirths and neonatal deaths. However, CDA is not routinely practiced in South Asian countries due to religious beliefs, lack of expertise, and lack of resources. Minimally invasive tissue sampling (MITS) has been recommended as a less mutilating and less expensive alternative to CDA for obtaining tissues for analysis. The present study aims to evaluate the yield of lung tissue and histological findings using MITS as part of a cause of death analysis for stillborns and preterm neonatal deaths. METHODS: Data were collected during an observational multicenter prospective study called the Project to Understand and Research Preterm birth and Stillbirth (PURPOSe) conducted in India and Pakistan. After obtaining written informed consent from parents, the eligible stillbirths and neonatal deaths were subjected to MITS using a standard protocol. The tissues were obtained from both lungs for histological and microbiological analysis. RESULTS: At both sites, a total of 453 stillbirths and 352 neonatal deaths underwent MITS. For stillbirths and neonatal deaths, the yield of lung tissue using MITS was high (92%). Intrauterine fetal distress and respiratory distress syndrome were the leading lung pathologies reported in stillbirths and neonatal deaths, respectively. CONCLUSIONS: MITS appears to be a reasonable alternative to CDA in obtaining and evaluating lung tissue to inform accurate cause of death analysis in stillbirth and preterm deaths.

Intra-abdominal Follicular Dendritic Cell Sarcoma (FDCS): Series of 18 cases of a rare entity from Pakistan.

OBJECTIVES: Follicular Dendritic Cell Sarcoma (FDCS) is a rare neoplastic proliferation of dendritic cells which are immune accessory cells found in both lymphoid and non-lymphoid organs. FDCS can thus occur in lymph nodes as well as non-lymphoid organs. Intraabdominal FDCS is even rarer. Our aim was to describe the clinical and morphological features of intra-abdominal FDCSs diagnosed in our practice and to review published literature on FDCSs including intra-abdominal FDCSs. METHODS: All cases of FDCSs diagnosed between January 1, 2008 and December 31, 2019 were included in the study. Slides of the cases were reviewed and clinical follow up was obtained. RESULTS: A total of 18 cases of intraabdominal FDCS were diagnosed during the study period. Age range was 17 to 55 years. Mean and median ages were 28 and 29 years respectively. Of the 18 patients, 11 were male and 7 were females. Colon was involved in 9 cases and appendix in 2 cases. 9 cases were received as resection specimens while 9 cases were received as slides and blocks for second opinion. Tumor size ranged from 2.7 to 26 cm. Average tumor size in these 9 cases was 8.2 cm and in 6 of these 9 cases, tumor size was greater than 6 cm in largest dimension. Grossly, tumors were nodular or polypoid and had a fleshy, grey white, homogeneous cut surface. Histologically, all 18 cases showed proliferation of plump to spindle shaped cells arranged in a fascicular or storiform pattern. Tumor cells had mild to moderately pleomorphic spindle to ovoid vesicular nuclei with fine chromatin and inconspicuous to variably conspicuous nucleoli, and moderate amount of pale eosinophilic cytoplasm. Mitotic activity was usually brisk. CD21 and CD23 were positive in all 18 cases. Resection margins were negative in all 9 resection specimens. Lymph nodes positive for metastases were seen in 4 cases. Follow up was available in 13 cases. Recurrence was seen in 6 patients, out of which 3 patients died of disease 15, 17- and 24-months following resection. 1 patient with appendiceal FDCS was free of disease almost 12 years after surgery but recently developed recurrence and is currently undergoing chemotherapy. 6 patients were alive and well at the time of follow-up 5 to 68 months after resection. None of them had developed recurrence or metastases at the time of follow up. 8 of the 13 patients received chemotherapy and/or radiotherapy post-surgical resection. CONCLUSION: Colon was involved in 9 of our 18 cases. Lymph nodes were positive for metastases in 4 out of 9 resection specimens. All cases were diagnosed based on morphology supported by positivity for immunohistochemical stains CD21 and CD23. Histological factors associated with aggressive behavior were seen in 14 cases. Majority of patients had an aggressive clinical course.

Histopathological effects on stomach, liver and kidney associated with Cedrus deodara root oil in ulcer induced rats (Wistar strain).

Cedrus deodara have been used traditionally in ayurvedic system against peptic ulcer. Present work is concerned with the determination of histopathological effects in ethanol induced ulcer on rats (Wistar Strain) treated with Cedrus deodara root oil at a dose of 200mg/kg and comparison of its antiulcer activity against control, positive control and standard anti-ulcer drug (Omeprazole). The aim was to find out the antiulcer effect of Cedrus deodara root oil and to observe histopathology of liver, kidney as well. 120 Albino rats were taken and divided into four groups i.e. A, B, C and D designated as control, positive control, standard and treated groups respectively. Normal and intact general architecture of mucosa and submucosa layers of stomach observed. No significant changes observed in thickness of epithelium, no inflammatory cells were present on the mucosa and submucosal layer and gastric glands were normal. Liver of albino rats, showed no dilation and congestion in central as well as portal vein. Kidney of albino rats exhibited no shrinkage in glomeruli, no congested and dilated renal corpuscles, neither hemolysis nor congested and dilated renal tubules were seen. It is concluded that C. deodara root oil has anti-ulcer properties without effecting kidney and liver tissues.

Congenital (infantile) fibrosarcoma of the scalp: a case series and review of literature.

INTRODUCTION: Congenital infantile fibrosarcoma (CIFS) is a soft tissue sarcoma of infants mainly involving lower extremities usually presenting during the first year of life. A subset of cases occur in the head and neck, but scalp involvement is exceptionally rare. PATIENTS AND METHODS: We report clinicopathological features of three cases of CIFS involving the scalp diagnosed between 2011 and 2012. RESULTS: The ages of the three patients at the time of diagnosis ranged from 12 to 90 days (mean 48 days). All were males and presented with scalp swelling at birth which grew rapidly in size. The tumor was located in the left temporal region in two cases and the right temporoparietal region in one case. On imaging, underlying bone involvement was noted in two cases. The mean size of the resected tumors was 8 cm. All cases exhibited a cellular tumor arranged in sheets of uniform oval to spindle cells, increased mitosis, and hemangiopericytoma-like vessels. All patients are alive after a mean follow-up of 39.6 months. Recurrence was seen in one case due to incomplete excision. No metastasis was seen in any of the cases. CONCLUSION: CIFS of the scalp is rare and carries a good prognosis. Underlying bone erosion is rare but was noted seen in two of our cases. A male predominance was seen in our cases.

Pleomorphic lobular carcinoma of the male breast with axillary lymph node involvement: a case report and review of literature.

BACKGROUND: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast. CASE PRESENTATION: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. Physical examination revealed bilateral gynaecomastia along with a well circumscribed subareolar mass and palpable lymphadenopathy in the ipsilateral axilla. The breast nodule revealed atypical cells on fine needle aspiration biopsy and the patient underwent a modified radical mastectomy after systemic surveillance was negative for metastatic disease. The lesion was reported as grade III pleomorphic lobular carcinoma with a lack of E-cadherin expression on immunohistochemistry and the neoplastic cells exhibited strong positivity for estrogen receptor in the absence of Her2 gene amplification. Six out of the eleven dissected regional lymph nodes showed evidence of disease. The patient completed 4 cycles of adjuvant chemotherapy without evidence of recurrent disease and was subsequently lost to follow up. CONCLUSIONS: Although invasive lobular carcinomas comprise 12% of all female breast cancers, they are very rare in males due to lack of acini and lobules in the normal male breast. Pleomorphic lobular carcinoma, an aggressive variant of ILC is even rarer in males. Chronic consumption of ethanol by our patient may have resulted in some degree of hepatic impairment with resultant hyperestrogenism. This in theory may have been the cause of his gynaecomastia, resultant breast cancer and is a plausible explanation for development of the invasive lobular subtype in a male. The prognosis and clinicopatholocial features of pleomorphic lobular carcinoma in men are less clearly defined due to its rarity. Additional studies are hence necessary to improve our understanding of this disease in males.

Lymphomatosis Cerebri: A diagnostic dilemma.

Background: Lymphomatosis cerebri (LC) is a rare manifestation of primary central nervous system lymphoma (PCNSL) with only a few cases reported in the literature, appearing as diffuse infiltrating process rather than a solitary mass. It is a non-Hodgkin's type of lymphoma and is usually of the B-cell type origin. Purpose: We intend to report this unique case of LC which came across as a diagnostic challenge. Methods: A 53-year-old gentleman presented with complaints of two episodes of seizures 24 h apart followed by postictal confusion for 10-15 min. He underwent multiple MRI scans and underwent a biopsy of the lesion which reported infection, but he did not benefit from the treatment. Result: The imaging was reviewed, suspicion of LC was raised and a review of histopathology was requested which later confirmed primary CNS lymphoma. Conclusion: LC is a rare but established manifestation of PCNSL which mimics multiple other conditions. Understanding of the imaging pattern is important in making the diagnosis and differentiating it from other mimic conditions.

Duodenal stricture secondary to IgG4-related chronic sclerosing duodenitis-A case report with review of the literature.

Key Clinical Message: This case highlights the importance of a definite diagnosis of an IgG4-related chronic sclerosing duodenitis based on histological and radiological findings to rule out any malignancy in the mass. While dealing with patients having concentric duodenal thickening resulting in stricture formation, one should think of inflammatory etiology as well. IgG4-related disease is one of these inflammatory disorders where we see soft tissue thickening without a large mass or any associated lymphadenopathy as in our case. Abstract: Immunoglobulin G4-related disease (IgG4-RD) is distinguished as an infiltration of IgG-4-positive plasmacytes involving inflammatory lesions across multiple organs which is accompanied by raised IgG4 levels in the serum. Several inflammatory disorders are recognized as part of the IgG4-RD family based on shared histopathological features, which include Mikulicz's disease, chronic sclerosing sialadenitis, or Riedel's thyroiditis. Our case highlights a distinctive presentation of IgG4-related diseases; a 58-year-old man presenting with duodenal stricture highly suspicious of a duodenal mass/ampullary mass later found to be due to IgG4-related sclerosing duodenitis with negative malignancy on biopsy. We present the diagnostic challenges faced and relevant findings noted.

Pediatric neuropathology practice in a low- and middle-income country: capacity building through institutional twinning.

Background: Accurate and precise diagnosis is central to treating central nervous system (CNS) tumors, yet tissue diagnosis is often a neglected focus in low- and middle-income countries (LMICs). Since 2016, the WHO classification of CNS tumors has increasingly incorporated molecular biomarkers into the diagnosis of CNS tumors. While this shift to precision diagnostics promises a high degree of diagnostic accuracy and prognostic precision, it has also resulted in increasing divergence in diagnostic and management practices between LMICs and high-income countries (HICs). Pathologists and laboratory professionals in LMICs lack the proper training and tools to join the molecular diagnostic revolution. We describe the impact of a 7-year long twinning program between Canada and Pakistan on pathology services. Methods: During the study period, 141 challenging cases of pediatric CNS tumors initially diagnosed at Aga Khan University Hospital (AKUH), Karachi, were sent to the Hospital for Sick Children in Toronto, Canada (SickKids), for a second opinion. Each case received histologic review and often immunohistochemical staining and relevant molecular testing. A monthly multidisciplinary online tumor board (MDTB) was conducted to discuss the results with pathologists from both institutions in attendance. Results: Diagnostic discordance was seen in 30 cases. Expert review provided subclassification for 53 cases most notably for diffuse gliomas and medulloblastoma. Poorly differentiated tumors benefited the most from second review, mainly because of the resolving power of specialized immunohistochemical stains, NanoString, and targeted gene panel next-generation sequencing. Collaboration with expert neuropathologists led to validation of over half a dozen immunostains at AKUH facilitating diagnosis of CNS tumors. Conclusions: LMIC-HIC Institutional twinning provides much-needed training and mentorship to pathologists and can help in infrastructure development by adopting and validating new immunohistochemical stains. Persistent unresolved cases indicate that molecular techniques are indispensable in for diagnosis in a minority of cases. The development of affordable alternative molecular techniques may help with these histologically unresolved cases.

Capacity building for pediatric neuro-oncology in Pakistan- a project by my child matters program of Foundation S.

Introduction: Initiated in June 2019, this collaborative effort involved 15 public and private sector hospitals in Pakistan. The primary objective was to enhance the capacity for pediatric neuro-oncology (PNO) care, supported by a My Child Matters/Foundation S grant. Methods: We aimed to establish and operate Multidisciplinary Tumor Boards (MTBs) on a national scale, covering 76% of the population (185.7 million people). In response to the COVID-19 pandemic, MTBs transitioned to videoconferencing. Fifteen hospitals with essential infrastructure participated, holding monthly sessions addressing diagnostic and treatment challenges. Patient cases were anonymized for confidentiality. Educational initiatives, originally planned as in-person events, shifted to a virtual format, enabling continued implementation and collaboration despite pandemic constraints. Results: A total of 124 meetings were conducted, addressing 545 cases. To augment knowledge, awareness, and expertise, over 40 longitudinal lectures were organized for healthcare professionals engaged in PNO care. Additionally, two symposia with international collaborators and keynote speakers were also held to raise national awareness. The project achieved significant milestones, including the development of standardized national treatment protocols for low-grade glioma, medulloblastoma, and high-grade glioma. Further protocols are currently under development. Notably, Pakistan's first pediatric neuro-oncology fellowship program was launched, producing two graduates and increasing the number of trained pediatric neuro-oncologists in the country to three. Discussion: The initiative exemplifies the potential for capacity building in PNO within low-middle income countries. Success is attributed to intra-national twinning programs, emphasizing collaborative efforts. Efforts are underway to establish a national case registry for PNO, ensuring a comprehensive and organized approach to monitoring and managing cases. This collaborative initiative, supported by the My Child Matters/Foundation S grant, showcases the success of capacity building in pediatric neuro-oncology in low-middle income countries. The establishment of treatment protocols, fellowship programs, and regional tumor boards highlights the potential for sustainable improvements in PNO care.

Madurella mycetomatis as an agent of brain abscess: case report and review of literature.

Fungal cerebral abscesses are rare and usually seen in immunocompromised individuals. We report a case and review published literature of Madurella mycetomatis as an agent of cerebral abscess. We found contiguous head and neck infections to be the principal cause of cerebral maduromycosis caused by M. mycetomatis. Early recognition of Madurella spp. as the causative agent is essential to avoid cerebral spread.

Postoperative radiotherapy for high-grade primary cardiac spindle cell sarcoma: a rare entity.

A patient in her early 20s presented with blood-stained sputum and shortness of breath. Initially, she was treated for pneumonia. Later, upon exacerbation of symptoms, further investigations were done which exhibited a left atrial mass causing compression of contralateral atrium. She underwent surgical resection of the mass, which was initially mistaken as myxoma. However, histopathological correlation revealed spindle cell sarcoma with focal myogenic differentiation. This case report highlights the role of Radiation Therapy in adjuvant setting with promising impact on improving local control after R2 resection. Cardiac spindle cell sarcoma, being one of the rarest cardiac tumours reported to date, warrants establishment of a Rare Tumour Multidisciplinary Team for management of such malignancies.

Giant Central Nervous System Aspergilloma Mimicking Butterfly Neoplasm of the Corpus Callosum.

Radiological presentation of central nervous system (CNS) aspergillosis is variable and depends on the immune status of the patients. Typical features of meningoencephalitis, infarction, abscess, and mycotic aneurysms commonly occur in immunocompromised patients. A rare mass-like or tumoral form of cerebral aspergillosis has been described mostly in immunocompetent patients which results in a diagnostic dilemma, thus potentially causing a delay in the management. We present a case of a large CNS aspergilloma mimicking an infiltrative callosal neoplasm in a young immunocompetent patient. Careful evaluation of imaging features, anatomical location, enhancement pattern, concomitant sinonasal and orbital extension, and angio-aggressive nature of the mass lesion with a high index of suspicion can help diagnose CNS aspergillosis in such patients.

Temporal impacts of road safety interventions: A structural-shifts-based method for road accident mortality analysis.

Extensive prior research has statistically analyzed the impact of infrastructural, policy, and environmental factors on road accidents, injuries, and mortalities. Most of these studies assumed long-term temporal stability in road safety data. These studies were later criticized for ignoring structural shifts in data over time caused by varying systemic influences such as socioeconomic and environmental factors, as well as major changes to road safety rules and networks. In this work, we proposed a novel four-phase methodology that identifies structural shifts or breaks in the road safety data and subsequently evaluates the role of various factors (including road safety interventions) in causing these breaks. The method is generalized, allowing different modeling bases and assumptions on the underlying data distribution. To demonstrate the merits of this methodology, we used it to investigate road accident mortality patterns in the Eastern Province of Saudi Arabia and its subregions for the period 2010-2020, when a series of road safety interventions were introduced. The case study analysis revealed the varying impact of these interventions at both the provincial and governorate levels. These results can be used to evaluate the efficacy of road safety interventions. The lessons learned can help to develop more robust road safety management programs.

Saudi Arabian road accident mortality and traffic safety interventions dataset (2010-2020).

Increased traffic volumes worldwide have resulted in an increased number of road accident injuries and mortalities. This global phenomenon motivated the United Nations (UN) to initiate a decade-long global road safety plan in 2010. In response, Saudi Arabia concurrently initiated a comprehensive road safety program, supported by detailed and comprehensive road safety data for the Eastern Province (EP) of Saudi Arabia. The contributed EP-Traffic-Mortality-and-Policy-Interventions Dataset provides multidimensional road safety data for 2010-2020 via two primary and five secondary data subsets. The first primary subset provides road accident mortality data. The five secondary data subsets reflect road accident mortalities at different time scales and administrative (provincial or governorate) levels. The second primary subset provides details of traffic safety policy interventions implemented during the same period. Researchers and policymakers can use this comprehensive dataset to study accident mortality patterns across various geospatial and time scales and analyze the effectiveness of policies intended to mitigate road accident mortalities.

The many faces of glioblastoma: Pictorial review of atypical imaging features.

Glioblastoma is an aggressive primary central nervous system tumour that usually has a poor prognosis. Generally, the typical imaging features are easily recognisable, but the behaviour of glioblastoma multiforme (GBM) can often be unusual. Several variations and heterogeneity in GBM appearance have been known to occur. In this pictorial essay, we present cases of pathologically confirmed GBM that illustrate unusual locations and atypical features on neuroimaging, and review the relevant literature. Even innocuous-looking foci, cystic lesions, meningeal-based pathology, intraventricular and infra-tentorial masses, multifocal/multicentric lesions and spinal cord abnormalities may represent GBM. We aim to highlight the atypical characteristics of glioblastoma, clarify their importance and list the potential mimickers. Although a definitive diagnosis in these rare cases of GBM warrants histopathological confirmation, an overview of the many imaging aspects may help make an early diagnosis.