Effect of Gender on Metabolic and Neurodevelopmental Parameters of Postnatally Growth-Restricted Rats Undergoing Catch-Up Growth.

OBJECTIVE: To determine the long-term effects of early postnatal malnutrition and various degrees of catch-up growth on metabolic (serum glucose, leptin, triacylglycerides) and neurodevelopmental parameters (learning and memory) among male and female rodent models, mimicking human preterm infants. STUDY DESIGN: Randomized controlled trial. Place and Duration of the Study: CMH Multan Insitute of Medical Sciences, from September 2021 to December 2021. METHDOLOGY: This study included 142 neonatal Wister rats, stratified into subgroups to mimic the human preterm infant model of postnatal malnutrition and catch-up growth. Metabolic consequences were assessed via serum analysis of glucose, leptin, and triacylglycerides. The neurocognitive comparison was made among subgroups via a passive avoidance test. Gender-specific comparison of all quantitative parameters was made among subgroups. RESULTS: Malnourished rats with accelerated catch-up growth achieved similar weight gain as normally fed rats when provided with adlibitum feeding in both males (p = 0.92) and females (p >0.99). Rats undergoing accelerated catch-up growth exhibited higher fasting serum glucose levels compared to those undergoing no, or normal catch-up growth (p <0.001). Malnourished female rats undergoing accelerated (p = 0.007), or no catchup growth (p = 0.004) exhibited significant deficits in learning and memory as compared to normally fed rats. Female malnourished rats with normal catchup growth exhibited no neurocognitive deficit as compared to normally fed rats (p = 0.08). CONCLUSION: Accelerated catch-up growth effectively addresses somatic growth disparities, while normal catch-up growth offers more favourable metabolic and neurodevelopmental outcomes. Particularly, female malnourished rats exhibited poor neurodevelopment in response to both accelerated and no catch-up growth. Gender-specific variations in neurodevelopment underscore the need for personalised care approaches for preterm nutritional care. KEY WORDS: Growth retardation, Leptin, Extrauterine growth restriction, Malnutrition, Neurodevelopment.

A fetus with a mass in the oral cavity: A rare case of large oral immature teratoma.

Oral teratoma is a congenital neoplastic lesion with an incidence of 2%-9% of all teratomas. It comprises variable amounts of all three germ cell layers. The lesion is graded on histology depending upon the presence of immature components. The most common sites of presentation are the sacrococcygeal area and head and neck with slight female predominance. Our report is based on a case that was received for histopathological evaluation. It consisted of a 20-week fetus with a huge mass protruding from oral orifice measuring 10.8 × 6.7 cm. Histological examination of the tumor revealed immature teratoma-oropharynx.

Extensive Cytomegalovirus Gastroduodenitis Causing Gastric Outlet Obstruction in an Immunocompetent Patient.

Cytomegalovirus (CMV) has been extensively researched in immunocompromised people, causing conditions such as colitis, retinitis, esophagitis, encephalitis, and pneumonitis. However, there are limited data on how the disease presents itself in immunocompetent hosts, apart from a self-limited mononucleosis-like syndrome. This case report presents CMV gastroenteritis causing gastroduodenal obstruction in an immunocompetent woman. It is important to consider CMV as a potential cause of various gastric pathologies in immunocompetent people. Further research is necessary to establish guidelines for diagnosing and treating this pathogen.

A Curious Case of Primary Gastric Mucosal Melanoma.

Malignant melanoma is a neoplasm of melanin-producing cells predominantly of cutaneous origin, which uncommonly develops within gut mucosa. We present the case of a 58-year-old woman with complaints of abdominal pain, loss of appetite and weight. Esophagogastroduodenoscopy revealed a gastric mass and systemic imaging demonstrated widespread nodal and bilateral adrenal gland involvement. Histopathology of the gastric mass confirmed primary malignant mucosal melanoma of the stomach. The patient received three cycles of Nivolumab but did not respond, and thus, was then offered best supportive care. Although infrequent, mucosal melanoma can arise from the gastrointestinal tract, and in contrast to the cutaneous form, advanced disease usually has a dismal prognosis and responds poorly to immune checkpoint inhibitors. Primary gastric melanoma is an aggressive disease that is diagnosed by exclusion after the differential diagnosis of metastasis from a cutaneous or unknown primary site has been conducted. If available, patients with treatment-naïve mucosal melanoma should be considered for enrollment in clinical trials.

Intrapulmonary schwannoma presenting as an asymptomatic lung mass: a case report.

BACKGROUND: Schwannomas are solitary well-circumscribed encapsulated benign tumors that exhibit Schwann cell differentiation, and arise directly from myelinated peripheral or central nerves. Although they are usually asymptomatic and found incidentally, schwannomas can cause symptoms due to compression of nearby structures which, depending on the location, can make clinical presentations widely variable. Despite their rarity, schwannomas have been documented in a number of locations including the limbs, cerebellopontine angle, posterior mediastinum, and, far more infrequently, the lungs. CASE PRESENTATION: In this article, we report an incidental finding of an intrapulmonary schwannoma in a 59-year-old Pakistani woman who was grossly asymptomatic upon presentation to the cardiothoracic surgery clinic. An [18F]fluorodeoxyglucose positron emission tomography/computed tomography scan revealed a lobulated soft-tissue lesion measuring 23 mm × 23 mm in the lower lobe of the right lung. A computed tomography-guided core biopsy of the mass was performed, which revealed a benign spindle cell lesion based on histopathological examination and immunohistochemical staining. The mass was surgically resected via a right lower lobectomy, and subsequently confirmed to be an encapsulated neoplastic lesion composed of well-differentiated Schwann cells. There were no short- or long-term complications, morbidities, or recurrences based on 1-year follow-up. CONCLUSION: This report underscores the predominantly asymptomatic nature of schwannomas and reemphasizes the efficacy of surgical resection as a safe and curative procedure for a tumor of this nature. Albeit very rare, intrapulmonary schwannomas can be considered a differential diagnosis when encountering solitary asymptomatic pulmonary nodules or masses.

In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene.

BReast CAncer gene 1 (BRCA1)-a tumor suppressor gene plays an important role in the DNA repair mechanism. Several BRCA1 variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed in-silico analyses of nonsynonymous SNPs (nsSNPs) of the BRCA1 gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and in-silico analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as "damaging", based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as "probably damaging". These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the BRCA1 protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in BRCA1.

Low-grade fibromyxoid sarcoma incidentally discovered as an asymptomatic mediastinal mass: a case report and review of the literature.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor characterized by bland histological features and aggressive clinical course. The most common anatomic locations of occurrence are the lower extremities, thorax, inguinal area, and upper limbs. Primary mediastinal sarcomas are even rarer. To the best of our knowledge, only seven cases of primary mediastinal LGFMS have been reported in the literature. Here, we report a case of primary mediastinal LGFMS. CASE PRESENTATION: A 26-year-old Pakistani man presented with fever and vomiting for the past 2 months. On a routine chest x-ray, a mediastinal mass was incidentally found. Computed tomography (CT) scan showed a large circumscribed lobulated soft tissue density mass lesion in an anterior mediastinum. Grossly, the resected mass measured 17.0 × 12.0 × 11.0 cm. The cut surface was gray white with a whorled-like appearance and foci of calcification and cystic changes. Histologically, a spindle cell lesion was seen with alternating myxoid and hyalinized areas. The shaped cells were arranged in bundles. Immunohistochemical staining showed positive reactivity patterns with MUC4 and focally for epithelial membrane antigen (EMA). The diagnosis was confirmed as LGFMS. The patient is free of symptoms and recurrence 22 months after the surgery. CONCLUSION: In conclusion, we report a rare case of primary mediastinal LGFMS in a young male patient that was discovered incidentally. Our patient is on regular follow-up to look for evidence of recurrence as these tumors are prone to recurrences.

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.

Fatal Invasive Gastrointestinal Fungal Infection in Three Non-immunocompromised Patients.

The importance and frequency of invasive fungal infections in different organs, including the gastrointestinal tract, has increased due to excessive use of aggressive immunosuppressive and immunomodulatory drugs in malignant diseases and organ transplantations as well as increased infections with the human immunodeficiency virus (HIV). Fungal infections in the small intestine or colon are usually part of a disseminated disease process and reach these organs through the bloodstream. Two of the patients were infants 10 and 15 days of age, while one was 23 years old. Patients presented with abdominal pain, intestinal obstruction, and rectal bleeding. Hirchsprung disease was suspected in the two infants. In the adult patient, the diagnosis was unclear. Mucormycosis was diagnosed in two out of three cases. It is imperative for clinicians to consider invasive mycosis in the differential diagnosis in patients of all ages with treatment-resistant severe abdominal pain, diarrhea and fever.

A Case Report of Triple-Positive Micropapillary Carcinoma of the Male Breast.

BACKGROUND: Micropapillary carcinoma (MPC), a morphologically distinct subtype of invasive ductal carcinoma, of the male breast is an exceedingly uncommon disease. CASE REPORT: Herein, we report a case of triple-positive MPC of the male breast with axillary lymph node involvement and no recurrence for over 2 years. Specifically, a 60-year-old male patient presented with a hard, elastic, and well-defined painless mass in the right breast. The patient underwent unilateral (right) modified radical mastectomy with axillary clearance. Histopathology revealed MPC grade 3 and metastasis in 16/16 lymph nodes. Hormone receptor analysis demonstrated strong positivity (total score 08) for estrogen/progesterone receptors and overexpression (score 3+) of human epidermal growth factor receptor 2. The patient received adjuvant chemotherapy (6 courses of CAF: cyclophosphamide, doxorubicin, and 5-fluorouracil), radiation, and tamoxifen. The patient has remained disease-free for over 2 years. CONCLUSION: This study demonstrates that triple-positive MPC of the male breast as a rare malignancy appears to respond promisingly to multimodality treatment.

HER2 Basolateral versus Circumferential IHC Expression Is Dependent on Polarity and Differentiation of Epithelial Cells in Gastric/GE Adenocarcinoma.

AIM: Antigenic expression in epithelial cells can be heterogeneous which may pose a problem in immunohistochemical (IHC) analysis of tumor markers, in particular, predictive markers like HER2. Studies have shown that epithelial cells have distinct apical and basolateral domains which are separated by tight junctions. The cell membrane in these two domains has a different composition of macromolecules and hence can have variable antigen expression on immunohistochemistry. In our study, we aimed to investigate this phenomenon of basolateral versus circumferential IHC staining of HER2 in gastric/GE adenocarcinoma. METHODS: We selected 45 cases of gastric/GE adenocarcinoma and evaluated equal number of specimens (15 each) showing well-differentiated, moderately differentiated, and poorly differentiated morphology. All cases had 3+ HER2 score as per CAP guidelines. HER2-membrane staining pattern in all specimens was analyzed. RESULTS: Cases with well-differentiated morphology showed only basolateral or lateral membrane staining in most cases. Poorly differentiated adenocarcinoma samples showed circumferential staining (both basolateral and luminal) in all cases with highly significant p value. Mixed staining pattern was observed in moderately differentiated cases. Diffuse expression of E-cadherin in well-differentiated adenocarcinoma and loss in poorly differentiated tumors were also statistically significant. CONCLUSION: These findings suggest that HER2 in gastric epithelium has a polarized distribution which is maintained by the fence function of tight junctions. With progression to high grade cancer, the glandular structural differentiation in gastric mucosa is lost, along with disruption of tight junctions. This leads to loss of cell polarity and migration of antigens across the membrane.

Post-traumatic fibrous dysplasia of the parietal bone: A rare entity.

Fibrous dysplasia (FD) is a rare fibro-osseous lesion in which normal bone is replaced by abnormal fibrous tissue. Although a congenital disorder, a single case report of traumatic etiology had been described in the literature. We report a case of monostotic FD of the parietal calvarium in a 21-year-old female patient who presented to us with a single swelling in the parietal region been noticed after head injury sustained at the age of 7 years. After imaging investigations, the lesion was excised via craniotomy followed by cranioplasty in the same sitting. The histopathological evidence was suggestive of FD. To the best of our knowledge, this is the second case of a posttraumatic cranial FD and the first case describing the growing mass in the parietal bone secondary to head injury.

Glomus Tumor of Trachea in an Adult Male.

Glomus tumors most commonly occur in distal extremities, particularly in the subungual region. The origin of these tumors is modified smooth muscle cells of glomus bodies. Trachea is one of the rare sites where normal glomus bodies may be sparse or absent, so occurrence of glomus tumor in trachea is very rare. Only 30 cases have been reported in the literature so far. In this case report, the authors describe a very rare and in fact first case of glomus tumor of trachea in a 45-year male Pakistani patient.

Spectrum of cytological findings in patients with neck lymphadenopathy--experience in a tertiary care hospital in Pakistan.

INTRODUCTION: Lymph adenopathy is of great clinical significance as underlying diseases may range from a treatable infectious etiology to malignant neoplasms. In fact it is also essential to establish that the swelling in question is a lymph node. Fine needle aspiration cytology (FNAC) plays a vital role in solving these issues, nowadays being recognized as a rapid diagnostic technique because of its simplicity, cost effectiveness, early availability of results, accuracy and minimal invasion. FNAC is particularly helpful in the work-up of cervical masses and nodules because biopsy of cervical adenopathy should be avoided unless all other diagnostic modalities have failed to establish a diagnosis. OBJECTIVE: To determine the epidemiological and cytomorphological patterns of enlarged neck nodes. STUDY DESIGN: This retrospective observational study was performed at the Section of Histopathology, Aga Khan University Hospital (AKUH), Karachi, Pakistan. MATERIALS AND METHODS: Three Hundred and seventy seven (377) neck swelling specimens obtained over a period of two and a half years registered from different regions of Pakistan were selected. Data were analyzed using SPSS 17. RESULTS: Of a total of 377 cases of FNAC performed on neck nodes, the most frequent cause of lymphadenopathy was found to be tuberculosis with 199 cases (52.7%), followed by reactive lymphoid hyperplasia with 61 cases (16.1%). Metastatic carcinoma was found to be the third most common cause with 33 cases (8.7%). A diagnosis of lymphoproliferative disorder was rendered in 21 cases (5.5%). Acute and chronic non-specific inflammation was seen in 16 cases (4.2%). In 47 cases (12%) FNAC was inconclusive. CONCLUSION: In our study, the predominant cause of enlarged neck nodes was tuberculous lymphadenitis, followed by reactive lymphadenitis and malignant neoplasm, especially metastatic carcinoma and lymphoma. FNAC was helpful in establishing the diagnosis in approximately 98% of the cases.