Introduction: Gastrointestinal basidiobolomycosis is an uncommon invasive fungal infection caused by Basidiobolus ranarum, an environmental mould endemic to the arid south-west of Saudi Arabia and to a handful of other hot, dry regions. Its non-specific presentation routinely invites misdiagnosis as inflammatory bowel disease, tuberculosis or malignancy, and extension to the biliary tree is decidedly rare. Case Presentation: We report a 25-year-old Saudi woman who developed chronic watery diarrhoea and pronounced weight loss two months after her first delivery. Severe microcytic anaemia, leukocytosis, a very high erythrocyte sedimentation rate and multisegmental colonic wall thickening were initially attributed to inflammatory bowel disease complicated by Clostridioides difficile colitis. She subsequently required cholecystectomy for acalculous cholecystitis and then deteriorated, with gastric outlet obstruction and collections at the gallbladder bed. Re-examination of the gallbladder specimen revealed broad, pauci-septate hyphae enveloped by the Splendore-Hoeppli phenomenon, and culture yielded an isolate phenotypically identified as B. ranarum. Voriconazole followed by itraconazole achieved near-complete clinical and radiological recovery. Discussion: We hypothesise that the early puerperium could represent a possible, though as yet unproven, window of susceptibility to this infection. Conclusions: In endemic regions, gastrointestinal basidiobolomycosis should be considered when presumed inflammatory bowel disease behaves atypically; deep tissue sampling is often decisive, and prolonged triazole therapy can achieve an excellent outcome.

Gastrointestinal histoplasmosis is an under-recognized manifestation of disseminated Histoplasma capsulatum infection. Its ileocecal predilection closely mimics intestinal tuberculosis (TB) and Crohn's disease, posing serious diagnostic challenges, particularly in TB-endemic regions. A 26-year-old immunocompetent male presented with a 3-month history of diffuse abdominal pain, hematochezia, and 16 kg weight loss. He had received 60 days of empirical four-drug anti-tubercular therapy (ATT) without improvement. Examination revealed cachexia, pallor, digital clubbing, pedal oedema, a hard palate ulcer, and small cervical lymphadenopathy. Investigations showed microcytic anemia, C-reactive protein (CRP) 143.35 mg/L, hypoalbuminemia (2 g/dL), hyponatremia, and fecal calprotectin of 1849.47 μg/g. Magnetic resonance enterography (MRE) suggested multi-segmental small bowel disease consistent with Crohn's disease. Sequential colonoscopies revealed ulcero-nodular lesions involving the distal ileum, ileocecal valve, and caecum. Initial biopsies were inconclusive. Repeat deep tissue biopsy from the caecum and ileocecal valve identified intracellular narrow-based budding yeast forms with eccentric nuclei, consistent with H. capsulatum. GeneXpert and Quantiferon-TB gold plus were negative. Cervical lymph node fine-needle aspiration cytology (FNAC) confirmed disseminated disease. HIV testing was negative. Itraconazole was initiated, followed by liposomal amphotericin B. On day 15, the patient developed catastrophic lower gastrointestinal hemorrhage, resulting in refractory hemodynamic collapse and death. Disseminated histoplasmosis should be considered in the differential diagnosis of ileocecal disease even in immunocompetent patients from TB-endemic regions. Histopathological confirmation through deep tissue biopsy is critical prior to immunosuppressive therapy. Delayed diagnosis carries significant mortality risk.

X-linked sideroblastic anemia (XLSA), caused by pathogenic variants in ALAS2, typically presents as microcytic anemia in males. However, heterozygous females occasionally exhibit an atypical macrocytic phenotype, often leading to diagnostic ambiguity and confusion with nutritional anemias or myelodysplastic syndromes. This study aims to characterize a novel ALAS2 variant and explore the possible mechanisms underlying macrocytosis in a female patient. We analyzed a 15-year-old female with an 8-year history of refractory macrocytic anemia. Diagnostic evaluations included hematological profiling, iron metabolism studies, and bone marrow examination. Whole-exome sequencing (WES) was employed to identify genetic variants, followed by Sanger validation. Protein structural modeling was performed using AlphaFold 3. The patient presented with severe macrocytic anemia, iron overload, and borderline folate status despite supplementation. WES identified a novel frameshift variant in ALAS2, c.1277dupT (p.M426Ifs*66), which supported the diagnosis of atypical XLSA. Structural modeling suggested that this variant alters the C-terminal region and may affect the conformation of the catalytic site, including the spatial configuration around Lys391, potentially impairing enzymatic function. Additional variants in DHX34, FANCI, and BRIP1 were also identified, although their potential contributions to the phenotype remain uncertain because functional evidence is lacking. In conclusion, we identified a novel, predicted loss-of-function variant in ALAS2 associated with early-onset macrocytic XLSA. Macrocytosis in this case may reflect a proposed "high-turnover" failure involving intramedullary attrition of mutant clones and stress-induced premature maturation of wild-type clones; however, this mechanism remains speculative. Secondary nutrient depletion and additional genetic variants may also contribute, although their roles require further validation. This case underscores the value of genomic sequencing in resolving atypical, refractory anemias in female patients and preventing long-term misdiagnosis.

Kaposi sarcoma (KS) is an angioproliferative neoplasm driven by human herpesvirus 8 (HHV-8), most commonly occurring in immunocompromised individuals, particularly in association with HIV infection. Although it classically presents with characteristic cutaneous or mucocutaneous lesions, nodal-predominant disease without skin involvement is uncommon and may pose a significant diagnostic challenge. We report the case of a 26-year-old man with recently diagnosed HIV infection and no prior antiretroviral therapy (ART) who presented with a two-week history of persistent fever, constitutional symptoms, abdominal pain, and progressive intolerance to oral intake. Initial evaluation revealed hemodynamic instability, severe microcytic anemia, marked thrombocytopenia, and progressive renal dysfunction. Imaging demonstrated generalized lymphadenopathy involving multiple nodal chains, bilateral pleural effusions, hepatosplenomegaly, and free intra-abdominal fluid, raising concern for a disseminated infectious, lymphoproliferative, or neoplastic process. CD4+ T-cell count and HIV viral load were not available in the clinical records reviewed; therefore, the degree of HIV-associated immunosuppression could not be quantitatively established. Given the persistence and progression of systemic manifestations, an excisional inguinal lymph node biopsy was performed. Histopathological examination demonstrated spindle-cell proliferation with irregular slit-like vascular spaces and erythrocyte extravasation. Immunohistochemical analysis showed nuclear positivity for HHV-8 latent nuclear antigen-1 (LNA-1), together with positivity for endothelial markers, confirming KS. No cutaneous or mucosal lesions suggestive of KS were identified during the clinical course, supporting an atypical presentation with predominant nodal involvement. The patient received supportive inpatient management, including hemodynamic stabilization and transfusional support. Despite an initial period of partial clinical stabilization, he subsequently developed acute respiratory failure with progressive clinical deterioration and died during the index hospitalization before the planned HIV- and KS-directed therapeutic strategy could be completed. Nodal KS without cutaneous involvement is an uncommon and potentially underrecognized presentation that may mimic HIV-associated lymphoma, disseminated opportunistic infections, and HHV-8-associated multicentric Castleman disease. This case emphasizes that KS should remain in the differential diagnosis of persistent lymphadenopathy and systemic manifestations in patients with HIV even when characteristic skin lesions are absent. Because imaging findings are nonspecific, early tissue biopsy with histopathological examination and HHV-8 immunohistochemistry is essential for definitive diagnosis. This paper was published earlier on the Research Square preprint server on April 14, 2026 (DOI: 10.21203/rs.3.rs-9363985/v1).

Microcytic anemia is among the most common hematological abnormalities in clinical practice and is usually attributable to iron deficiency, thalassemia traits, or anemia of inflammation. A small but clinically important subset of patients, however, has inherited disorders of iron metabolism or heme synthesis presenting with persistent, unexplained, familial, or iron-refractory microcytosis. Over the past decade, advances in the understanding of the hepcidin-ferroportin axis, erythroid iron regulation, standardized hepcidin assays, and next-generation sequencing have substantially refined diagnosis, while expert guidance for iron-refractory iron deficiency anemia (IRIDA) has refined management, and hepcidin-targeted therapies in early development signal a shift towards mechanism-based treatment, though their role in IRIDA remains investigational. This review provides an updated, clinically oriented framework for inherited microcytic anemias caused by defects in systemic iron homeostasis, cellular iron transport, mitochondrial iron utilization, and heme biosynthesis. We propose a contemporary diagnostic algorithm integrating clinical features, iron biomarkers, hepcidin assessment, and molecular testing, and review current and emerging therapeutic strategies. Early recognition enables accurate diagnosis, avoids inappropriate investigations and treatment, facilitates genetic counselling, and helps prevent irreversible organ damage, particularly in iron-overload disorders.

Burkitt lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma that most commonly presents in children with extranodal abdominal disease. Although the diagnosis is often prompted by gastrointestinal symptoms or a palpable abdominal mass, early manifestations may be subtle and nonspecific, delaying recognition. We present the case of a three-year-old boy who was initially evaluated during a routine well-child visit for short stature and found to have microcytic anemia consistent with iron-deficiency anemia (IDA). Eight days after initiating appropriate iron supplementation, he subsequently developed jaundice, a palpable abdominal mass, and progressive clinical decline. Further evaluation with imaging revealed multiple intraabdominal masses, and tissue biopsy confirmed sporadic Burkitt lymphoma with extensive intraabdominal involvement. This case highlights the importance of ongoing clinical reassessment and careful physical examination when patients fail to respond as expected to standard therapy, as seemingly common pediatric conditions may represent the earliest manifestations of an underlying malignancy.

Microcytic hypochromic anemia in dogs represents a persistent diagnostic challenge, particularly when differentiating between absolute iron deficiency and inflammation-driven functional iron restriction. Conventional biomarkers, including serum iron and ferritin, present important limitations in terms of sensitivity, specificity, and temporal resolution, restricting their ability to accurately reflect dynamic changes in iron metabolism. This review critically evaluates the diagnostic performance and clinical relevance of hepcidin and reticulocyte hemoglobin indices (CHr/RET-He) as advanced biomarkers of iron-restricted erythropoiesis in dogs. Reticulocyte indices provide a dynamic and near real-time assessment of iron availability at the level of erythropoiesis, enabling early detection of iron-restricted states and monitoring of therapeutic response. However, their diagnostic utility is limited by an inability to discriminate between underlying etiological mechanisms. In contrast, hepcidin, the central regulator of systemic iron homeostasis, provides mechanistic insight into iron metabolism. Its circulating concentrations decrease in absolute iron deficiency and increase in inflammation-mediated iron sequestration, thereby potentially facilitating etiological differentiation. Despite its diagnostic potential, clinical application remains limited by methodological variability, lack of assay standardization, and incomplete reference intervals in canine populations. The integration of functional biomarkers (CHr/RET-He) with a regulatory biomarker (hepcidin) is proposed as a complementary and physiologically grounded approach. This combined strategy may enhance diagnostic accuracy, support etiological classification, and facilitate clinical decision-making; however, its diagnostic performance has not yet been sufficiently validated in canine patients, and further prospective studies are required before routine clinical implementation can be recommended.

Lymphatic malformations are rare congenital vascular anomalies that most commonly affect the head and neck regions. Cervicofacial lesions extending into the oral cavity or upper airway can result in dysphagia, bleeding, malnutrition, and airway obstruction. Emergency assessment is particularly challenging because significant anatomic distortion can exist even when physiologic parameters remain stable, necessitating thorough airway evaluation and early anticipation of potential clinical deterioration.

Haemoglobin (Hb) variants arising from mutations in globin chains can alter red blood cell (RBC) parameters. This may complicate the interpretation of pregnancy-related haematological changes, particularly in sub-Saharan Africa, where both anaemia in pregnancy and Hb variants are highly prevalent. The association between these variants and red cell parameters among Ghanaian pregnant women remains insufficiently characterised. This cross-sectional study investigated the association between Hb variant phenotypes and red cell parameters, and assessed whether such variants were independently associated with anaemia among 400 pregnant women at the Ga West Municipal Hospital, Greater Accra Region, Ghana. Full blood counts and Hb phenotyping by cellulose acetate electrophoresis at pH 8.4 were performed. Multivariable linear and Firth's penalised-likelihood logistic regression models, adjusted for maternal age, body mass index, gestational trimester, parity and haematinic supplementation, were used to estimate associations. Phenotype distribution was HbA 73.2%, HbAS/HbAC 25.3% and HbS/HbC/HbSC 1.5%; anaemia prevalence was 87.5%. Compared with HbA, HbAS/HbAC carriers had lower haematocrit (adjusted β = -1.14%, p = 0.036), mean cell volume (adjusted β = -4.05 fL, p < 0.001), mean cell Hb (adjusted β = -0.89 pg, p = 0.005) and red cell distribution width-standard deviation (RDW-SD) (adjusted β = -2.79 fL, p < 0.001); HbS/HbC/HbSC reductions were larger for haematocrit (adjusted β = -6.29%, p = 0.005) and mean cell volume (adjusted β = -6.87 fL, p = 0.001). Hb phenotype was not independently associated with anaemia, but the adjusted odds of anaemia in the second trimester were significantly higher than in the first (adjusted odds ratio = 3.45, p = 0.001). Hb variant phenotypes were associated with a microcytic, hypochromic red cell profile, whereas gestational trimester, rather than phenotype, was the dominant correlate of anaemia. Given the single-centre, cross-sectional design and the small number of pregnant women with homozygous or compound heterozygous phenotypes, these findings are hypothesis-generating. They support phenotype- and trimester-aware interpretation of red cell parameters in antenatal care; however, whether such interpretation improves maternal outcomes requires evaluation in larger, multicentre studies.

Alpha- and beta-thalassemia are inherited hemoglobinopathies caused by defects in the α- and β-globin genes, with carrier states typically showing mild or no clinical manifestations. However, co-inheritance of different globin gene defects may result in a more severe or atypical phenotype. Here, we report a unique case of co-inherited rare -α[20.5] deletion, associated with α-thalassemia carrier status, and the common IVS-I-1 G > A (HBB: c0.92 + 1G > A) splice-site mutation, associated with β[0]-thalassemia trait. To our knowledge, this combination has not been previously reported.

Gastrointestinal leiomyosarcoma is a rare malignant smooth-muscle neoplasm that may be difficult to diagnose using superficial mucosal biopsy. A 44-year-old woman presented with chronic intermittent abdominal pain and microcytic hypochromic anemia. Retrograde single-balloon enteroscopy identified an ulcerated, stenosing lesion in the distal ileum, whereas six forceps biopsy specimens showed only inflammation and granulation tissue. Segmental ileal resection was therefore performed because malignancy remained strongly suspected. Histological examination demonstrated a spindle-cell neoplasm with focal myxoid change and marked mitotic activity. The tumor cells expressed smooth muscle actin, with focal desmin and calponin expression, and were negative for DOG1, CD34, pancytokeratin, S-100, and HMB45. Specialist pathological review supported the diagnosis of FNCLCC grade 3 ileal leiomyosarcoma. After multidisciplinary discussion, the patient received six cycles of individualized adjuvant chemotherapy. At the latest radiological assessment, approximately 32 months after surgery, there was no evidence of local recurrence or distant metastases. This case highlights the value of single-balloon enteroscopy in localizing suspicious small-bowel lesions despite nondiagnostic mucosal biopsies.

There was only one report of α-globin gene triplication identified in Northern Thailand. Moreover, the genotype and phenotype associated with α-globin gene triplication and its interactions with other types of thalassemia or hemoglobinopathy remain unclear. Therefore, this study aimed to analyze the genotype and phenotype of α-globin gene triplication and its co-inheritance forms found in this area.Blood samples anti-coagulated with ethylenediamine tetra acetic acid (EDTA) and the data of red cell indices were obtained from hospitals in Northern Thailand. The molecular analysis for detection of ααα[anti3.7] and ααα[anti4.2] triplications was performed using a single-tube multiplex-PCR. The β- and α-globin gene mutations were also analyzed using targeted next-generation sequencing (NGS).The α-globin gene triplication was found in 8 of 2,078 (0.38%) samples classified into five different genotypes. A microcytic-hypochromic anemia (MCV < 80 fL and MCH < 27 pg) was not found in samples with ααα[anti3.7] triplication alone while it was observed in the other genotypes. Moreover, the samples who coinherited with ααα[anti3.7] triplication and β-thalassemia had the lowest levels of MCV and MCH.The clinical and hematological features of the α-globin gene triplication varied when interacting with other forms of thalassemia or hemoglobinopathy. This information should be provided at genetic counseling and prenatal thalassemia diagnosis. However, the detection rate (0.38%) among referred samples may underestimate population prevalence, as it excludes individuals with normal red cell indices and hemoglobin levels. Thus, further large-scale population studies along the Northern Thailand are required to validate these findings.