Primary cutaneous malignant melanoma in Rett syndrome: Report of a case with nuclear features resembling herpes simplex virus cytopathic effects-a hitherto unrecognized morphological variant.

Rett syndrome (RTT) is a progressive neurological disorder, affecting females with mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). While MECP2 has been implicated in cancers of the breast, colon, and prostrate, cancer in patients with RTT is rare. We present a case of malignant melanoma in a patient with RTT, which additionally, displayed hitherto undescribed nuclear features, resembling herpes simplex virus cytopathic effects.

Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer.

Despite recent advances in colorectal cancer (CRC) treatment, a large proportion of patients show limited responses to therapies, especially in advanced stages. There is an urgent need to identify prognostic biomarkers and/or therapeutic targets in advanced stages, aiming to improve the efficacy of current treatments. We aimed to determine prognostic biomarkers in tumor tissue and circulation of CRC patients, with a special focus on T cell exhaustion markers. We found that mRNA levels of PD-1, TIM-3, CTLA-4, TIGIT, CD160, CD244, KLRG1, TOX2, TOX3, Ki-67, and PRDM1 were elevated in CRC tumor tissues. We also investigated differences in gene expression between early and advanced disease stages. We found that TOX and potentially TIM-3, CTLA-4, VISTA, TIGIT, KLRG1, TOX2, SIRT1, Ki-67, and Helios mRNA levels in tumor tissue were elevated in advanced disease stages, suggesting their potential roles in CRC progression. In contrast, PD-1 and CD160 levels in tumor tissue were downregulated in advanced stages. In the circulation of CRC patients, mRNA levels of PD-1, VISTA and LAG-3 were higher than those of healthy individuals. Moreover, in circulation, PD-1, CTLA-4 and TIGIT mRNA levels were reduced in advanced stages. Interestingly, levels of PD-1 in both tumor tissue and circulation were reduced in advanced stages, suggesting that targeting PD-1 in patients with advanced stages could be less effective. Altogether, these findings suggest some potential T cell exhaustion markers that could be utilized as prognostic biomarkers and/or therapeutic targets for CRC. However, further investigations and validations in larger cohorts are required to confirm these findings.

Florid biliary duct lesions in an AMA -positive patient in absence of cholestatic liver biochemistry.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease, diagnosed by the presence of anti-mitochondrial antibodies (AMA) or highly PBC-specific anti-nuclear antibodies, in the appropriate context of cholestatic liver biochemistry. We present a case with histological features of destructive granulomatous lymphocytic cholangitis affecting interlobular and septal bile ducts suggestive of PBC, with strong positive AMA, Anti-M2 and anti-nuclear dot, but with persistently normal alkaline phosphatase (ALP). On the contrary to previous reports suggesting that those individuals in whom ALP remains persistently below 1.5 times ULN appear to have a benign course and a better prognosis, our patient progressed to liver cirrhosis.

A malignant spiradenoma of the forehead: a case report and literature review.

Spiroadenomas, arising from sweat glands, are rare benign skin tumors primarily found as solitary nodules on the head, neck, and trunk. The malignant subtype, Spiradenocarcinoma (MSA), originating from benign spiradenomas, is extremely rare and occurs mainly in individuals over 50. MSA exhibits aggressiveness with higher metastasis rates and lower survival rates. Surgical excision is the standard management, supported by imaging modalities like MRI, CT-scan, and ultrasound. We present a 69-year-old female with a medical history of diabetes, hypertension, and dyslipidemia who presented in 2014 with multiple swellings on the forehead and left arm. Initial excisions revealed capillary hemangioma lesions. Subsequent visits involved the excision of further facial and body lesions, with some identified as intradermal nevi. In 2022, she presented to plastic surgery clinic with forehead swelling. The biopsy showed MSA lesion with involved margins. Thus, subsequent re-excision was carried out. One year later, she came with recurrent forehead swelling. Excision and direct closure of the lesion showed involvement of part of the subcutaneous tissue (fat globule) showing residual/recurrent MSA that is very close to nerve trunks. Malignant Spiradenomas (MSAs) usually arise from benign spiradenomas. Therefore, consideration is given to preemptive removal of these tumors due to their potential evolution. The primary treatment approach involves surgery, with a focus on wide local excision and a minimum margin of 1 cm to diminish the risk of metastasis. Vigilant follow-up is essential to promptly identify any recurrences or spreading.

Successful treatment of rare linear lichen planopilaris with Ixekizumab.

Background: Lichen planopilaris (LPP) is a lymphocytic primary cicatricial alopecia characterized by perifollicular erythema, follicular hyperkeratosis and scaring, resulting in permanent hair loss. Current treatment modalities, both topical and systemic, fail to achieve satisfactory and consistent results. As therapies fail to halt the inflammatory process, patients with LPP may face long-term disfigurement and significant psychological burden.Purpose: To initiate an efficacious targeted therapy with good tolerability and low side effect profile that will allow hair regrowth and prevent the development to disfiguring alopecia.Materials and methods: Here, we report on a case of rare LPP in a linear distribution (LLPP) involving the scalp and forehead failing to achieve satisfactory results with continued hair loss with multiple previous treatments.Results: Complete hair regrowth was achieved 12 weeks after treatment with an anti-psoriatic, anti-interleukin (IL)-17A/F antibody (Taltz, Ixekizumab, Lilly). Patient continued to display sustained efficacy with no reported side effects until 12 months on treatment.Conclusions: The present case underlines the viability of Ixekizumab as a possible first-line, targeted therapy for LPP and its variants with sustained efficacy. Multicenter trials are warranted to confirm the benefit of Ixekizumab as a successful targeted biologic treatment option for LPP and LLPP.

Unusual case of adult-onset cutaneous lupus erythematosus mimicking early mycosis fungoides.

Discoid lupus erythematosus (DLE) is a chronic variant of cutaneous lupus erythematous developing on sun-exposed areas in multi-morphic forms making diagnosis challenging. Clinical suspicion and prompt treatment are necessary to avoid permanent disfigurement, progression to systemic involvement and poor quality of life. We report a case of delayed DLE diagnosis in a 45-year-old man who presented with a new skin lesion mimicking the early stages of mycosis fungoides that prompted further investigation. Histopathological examination confirmed DLE and appropriate treatment was initiated. However, the atypical clinical presentation led to disseminated DLE and refractory disease control, resulting in scarring and cosmetic disfigurement.

Primary Sarcomas of the Larynx: A Case Series of Four Different Histopathologic Types.

Primary laryngeal sarcomas are rare. Their nomenclature and classification are similar to soft tissue counterparts; however, there are notable differences between clinical presentation, behavior, treatment, and follow-up. There is sparse information regarding the clinical features, biologic behavior, and treatment modalities of laryngeal sarcomas. To increase our understanding about these tumors, we describe herein an additional series of four cases of different pathologic types of laryngeal sarcomas, including low-grade chondrosarcoma, leiomyosarcoma, well-differentiated liposarcoma, and undifferentiated pleomorphic sarcoma. Our main aim is to upsurge awareness about the morphologic variations of laryngeal sarcomas, to avoid potential pitfalls during histopathologic examination. It is essential to ensure that correct diagnosis, subclassification, and grading are achieved for proper guidance of treatment and clinical follow-up at multidisciplinary team meetings.

Delayed Diagnosis of Indolent Systemic Mastocytosis as the Cause of Unexplained Skin Rash: A Case Report.

Mastocytosis is a heterogeneous group of disorders in which mast cells exhibit clonal proliferation that infiltrates one or more organs. In cutaneous mastocytosis, the mast cells infiltrate the skin only, whereas systemic mastocytosis is diagnosed when at least one extra-cutaneous site is involved, with or without the skin being affected. Given the rarity of mastocytosis and the fact that skin rash can be a manifestation of different conditions and many clinicians are not familiar with this disorder, an accurate diagnosis may be delayed. We report a delayed diagnosis of indolent systemic mastocytosis in a 40-year-old gentleman who had been complaining of an unexplained skin rash for 6 years.

Coinfection of HPVs Is Associated with Advanced Stage in Colorectal Cancer Patients from Qatar.

High-risk human papillomaviruses (HPVs) are considered risk factors in the origin of several human malignancies, such as breast, cervical, head and neck, as well as colorectal cancers. However, there are no data reported on the HPV status in colorectal cancer in the State of Qatar. Therefore, we herein examined the presence of high-risk HPVs (16, 18, 31, 33, 35, 45, 51, 52, and 59), using polymerase chain reaction (PCR) in a cohort of 100 Qatari colorectal cancer patients, and their association with tumor phenotype. We found that high-risk HPV types 16, 18, 31, 35, 45, 51, 52, and 59 were present in 4, 36, 14, 5, 14, 6, 41, and 17% of our samples, respectively. Overall, 69 (69%) of the 100 samples were HPV positive; among these, 34/100 (34%) were positive for single HPV subtypes, while 35/100 (35%) of the samples were positive for two or more HPV subtypes. No significant association was noted between the presence of HPV and tumor grade, stage, or location. However, the presence of coinfection of HPV subtypes strongly correlated with advanced stage (stage 3 and 4) colorectal cancer, indicating that the copresence of more than one HPV subtype can significantly worsen the prognosis of colorectal cancer. The results from this study imply that coinfection with high-risk HPV subtypes is associated with the development of colorectal cancer in the Qatari population.

Incidence and association of high-risk HPVs and EBV in patients with advanced stages of colorectal cancer from Qatar.

High-risk Human Papillomaviruses (HPVs) and Epstein - Barr virus (EBV) are present and involved in several types of human carcinomas, including cervical and, head and neck cancers. Nevertheless, their presence and association in the pathogenesis of colorectal cancer is still nascent. The current study explored the association between the high-risk HPVs and EBV and tumor phenotype in colorectal cancers (CRCs) in the Qatari population. We found that high-risk HPVs and EBV are present in 69/100 and 21/100 cases, respectively. Additionally, 17% of the cases showed a copresence of high-risk HPVs and EBV, with a significant correlation only between the HPV45 subtype and EBV (p = .004). While the copresence did not significantly associate with clinicopathological characteristics, we identified that coinfection with more than two subtypes of HPV is a strong predictor of advanced stage CRC, and the confounding effect of the copresence of EBV in such cases strengthens this association. Our results indicate that high-risk HPVs and EBV can co-present in human CRCs in the Qatari population where they could plausibly play a specific role in human colorectal carcinogenesis. However, future studies are essential to confirm their copresence and synergistic role in developing CRCs.

An integrated tumor, immune and microbiome atlas of colon cancer.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Visceral Basidiobolomycosis Causing Bowel Ischemia.

Basidiobolomycosis is a rare fungal infection caused by saprophyte Basidiobolus ranarum. It is rarely seen in healthy adult patients; however, it usually affects children. The commonly involved sites are skin and subcutaneous tissue, mostly found in the Middle East and the southwestern United States. The diagnosis is challenging because of the lack of specific clinical presentation and the absence of predisposing factors. In our case report, we discuss a 38-year-old male patient who presented with a 2-months history of right lower quadrant pain. Initially, his pain was intermittent and gradually increased in intensity; it localized to the right lower quadrant and radiated to the right flank region. No relieving or aggravating factors were noted. In addition, the patient mentioned a history of constipation, weight loss, decreased appetite, and vomiting-however, no history of fever, night sweats, trauma, or recent travel. The diagnosis was made based on computerized tomography (CT) guided biopsy of the mass, illustrating the findings of fungal hyphae with a gradual increase in the eosinophilic count since admission. The patient was managed using a combined medical and surgical approach, including surgical debulking of the mass and a well-monitored course of anti-fungal therapy. Gastrointestinal basidiobolomycosis infection (GBI) can present in many forms, with an increasing potential to invade the colon, ultimately forming an inflamed mass. Nonetheless, the presence of a mass invading the colon, adjacent vessels, and a retroperitoneal area, along with an increase in the number of eosinophil count in the Middle East region, should raise the suspicion of basidiobolomycosis fungal infection.

Refractory Hyperammonemic encephalopathy in Fibrolamellar hepatocellular carcinoma, a case report and literature review.

Fibrolamellar hepatocellular carcinoma is a rare type of hepatocellular carcinoma with unclear etiology. Its prevalence ranges from 0.6%-5%. One of the rare manifestations of FHCC includes hyperammonemic hepatic encephalopathy (HAE). Data regarding HAE in FHCC is limited to case reports, and much is unknown, including its precipitating factors, clinical course, and management. We have reported one such case of FHCC associated HAE and presented an extensive literature review on the topic. We report the case of a 26-year-old Pakistani male who was diagnosed with fibrolamellar hepatocellular carcinoma. On day five after the first chemotherapy, he presented with nausea, vomiting, and confusion. His serum ammonia level was raised, and he was treated with lactulose and rifaximin. The patient continued chemotherapy and had recurrent admissions with HAE. A detailed workup revealed acquired ornithine transcarbamylase deficiency. Ammonia level peaked at 694 umol/L during the clinical course of his disease. He received treatment with multiple ammonia scavengers, including sodium benzoate + phenylacetate, with relief of symptoms and reduction in ammonia level. The patient was eventually lost to follow-up. HAE presents as a paraneoplastic manifestation of FHCC. Patients have laboratory features suggestive of acquired ornithine transcarbamylase deficiency. There is a variable frequency of episodes reported in the literature. Most patients respond well to ammonia scavenger therapies rather than conventional HE management with lactulose or rifaxmin.

Atypical parathyroid adenoma: Series of two consecutive cases from a tertiary care hospital in Qatar.

INTRODUCTION: Atypical parathyroid adenomas (APA) are an uncommon cause of hypercalcemia and comprise a minority of parathyroid adenomas. PRESENTATION OF CASES: Case 1 - Egyptian male, 48 years old with history of type 2 diabetes mellitus, incidentally discovered increased serum of calcium level on routine investigation, was diagnosed as PHPT, US and MIBI scan showed large left inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA. Case 2 - Egyptian male, 60 years old, cardiac patient with history of diabetes, hypertension and multiple cardiac interventions, had nausea, vomiting, constipation abdominal pain, polyuria, polydipsia, and history of passing renal stones, hypercalcemia workup showed primary hyperparathyroidism (PHPT), MIBI was negative and SPECT scan suggested right inferior parathyroid adenoma, focused exploration and excision of the APA was undertaken, histopathology confirmed APA. DISCUSSION: APA are an uncommon cause of hypercalcemia and are responsible for a minority of parathyroid adenomas. Combined US and MIBI and SPECT scans can detect APA. Focused exploration and excision of the APA under general anaesthesia can completely remove the APA. CONCLUSION: Awareness of the physician and a high index of suspicion to symptoms or signs that could reflect an underlying PHPT is essential. Yearly biochemical and neck US follow up are required to detect any risk of recurrence or malignancy in the long term.

Subacute (De Quervain's) thyroiditis presenting as painful thyroid nodule suspicious of papillary thyroid carcinoma: Case report.

INTRODUCTION: We report a case of subacute thyroiditis (SAT) in a 29 -year-old female who presented with painful thyroid swelling. PRESENTATION OF CASE: Patient presented with neck pain, tender neck swelling and generalized fatigue. She had no history of neck or chest radiation or compressive symptoms. Ultrasound (US) imaging reveled bilateral nodules of the thyroid gland. Lymph nodes were unremarkable. FNAC was suspicious for papillary thyroid carcinoma. The patient was discussed at the thyroid multidisciplinary meeting, and after deliberation the decision was to offer the patient the choice of repeating FNAC of the bilateral nodules in one month or to proceed with total thyroidectomy. DISCUSSION: Despite being aware of the possibility that the final pathology could be benign, the patient insisted on total thyroidectomy, given that her FNAC results were suspicious of papillary thyroid carcinoma, and in order to avoid recurrence of the condition and the pain. Following the patient's preference, total thyroidectomy was performed, and surgery was not straightforward as intraoperatively, there was a diffusely inflamed gland. Histopathology findings revealed benign pathology. Follow up until 1.5 years showed that the patient was satisfied, and with normal voice. CONCLUSION: SAT is a painful but potentially self-limiting. In some cases, FNAC findings might be suspicious for papillary thyroid carcinoma. Treatment is mostly conservative, but if the pain is severe and the patient insists on surgery as in our case despite the possibility of the condition being of benign pathology, then surgery should be undertaken.

What you see might not be what you get: Analysis of 15 prospective cases of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

INTRODUCTION: Noninvasive follicular thyroid neoplasm with papillary-like nuclear (NIFTP) is a new entity. No previous study reported prospective cases, outlining using many quantitative and qualitative variables. METHODS: Retrospective analysis of all (15) prospective NIFTP cases diagnosed between 2017 and 2021 at our institution. Statistical quantitative analysis outlined demographic, history, ultrasound, histopathology and treatment characteristics. Qualitative analysis examined the cases, with details provided on three cases to highlight the different possible presentations and configurations. RESULTS: Mean age was 41.5 ± 9.91 years, 73.3% were females, and mean BMI was 29.49 ± 5.74 kg/m2. About 87% patients were symptomatic; 86.6% had neck swelling. Ultrasound (US) showed multiple nodules in 71.4% of cases. Fine-needle aspiration cytology (FNAC) showed that follicular lesion of undetermined significance (42.8%) was most common, followed by benign nodule (21.3%). Using the Bethesda System for Reporting Thyroid Cytopathology, 7 cases were category III, 3 category IV, 3 category II, and 1 category I. 60% of patients underwent total thyroidectomy. All cases were diagnosed postoperatively, 2 patients had additional papillary microcarcinoma. In 3 cases, the NIFTP site in the histopathology of resected specimen was different than the US-recommended site of the FNAC. CONCLUSION: We found discrepancies in the site and diagnosis of the preoperative US recommendation for the FNAC vs the postoperative histopathology of the specimen. These suggest that NIFTP might be incidentally and postoperatively diagnosed, irrespective of US or FNAC findings, hence its 'true' incidence might remain underestimated. As NIFTP cases higher BMI, Future research could predict preoperative diagnosis of NIFTP and explore associations with BMI.

Sausage digit: Isolated tuberculous tenosynovitis of the middle finger.

Isolated tuberculous tenosynovitis is a rare form of extra-pulmonary tuberculosis that frequently eludes assessment and constitutes diagnostic challenges.

Time equals sight: Sphenoid sinus aspergilloma with vision loss.

Sphenoid sinus aspergilloma (SSA) with visual loss has rarely been reported. Timely recognition and prompt surgical intervention are crucial to avoid permanent neurological consequences.