EP816 - Primary Colonic Undifferentiated Pleomorphic Sarcoma In HIV: An Extraordinary Diagnostic Challenge And Review Of Histopathological Implications

Purpose/Background: Primary undifferentiated pleomorphic sarcoma (UPS) of the colon is an exceptionally rare mesenchymal malignancy ( < 0.1% of colorectal cancers). Fewer than 60 cases have been reported, almost all in immunocompetent adults. Diagnosis is established only by exclusion through extensive histopathologic and immunohistochemical evaluation, as UPS lacks lineage-specific differentiation. This appears to be the first documented association of primary colonic UPS with HIV and a paraneoplastic leukemoid reaction in the peer-reviewed literature, underscoring the tumor's aggressive biology and the diagnostic complexity in immunocompromised hosts.

Methods/Interventions: A 69-year-old woman with long-standing, well-controlled HIV presented with progressive abdominal distension, anemia, and extreme neutrophilic leukocytosis. Evaluation comprised contrast-enhanced abdominopelvic CT, colonoscopy with multiple biopsies, comprehensive immunohistochemistry (IHC), and PET/CT staging, followed by multidisciplinary review (colorectal surgery, oncology, hematology, radiology, pathology). Imaging demonstrated a heterogeneous necrotic mass at the splenic flexure measuring up to approximately 11 cm with mesocolic stranding and free fluid, without obstruction. Colonoscopy revealed a large semipedunculated exophytic lesion; biopsy showed a vimentin-positive undifferentiated pleomorphic neoplasm lacking epithelial, hematolymphoid, melanocytic, myogenic, and GIST markers. Given diagnostic uncertainty and rapid clinical progression, the team proceeded with an exploratory laparotomy, transverse colectomy with D2 lymphadenectomy, and creation of a terminal colostomy, along with standard perioperative critical-care management and broad-spectrum antimicrobial therapy.

Results/Outcomes: Gross pathology of the transverse colectomy specimen revealed a 16-cm intramural, lobulated mass with two pedunculated mucosal nodules (5.5 and 4.5 cm). Histology showed sheets and fascicles of pleomorphic spindle and polygonal cells with marked atypia, brisk atypical mitoses, inflammatory infiltrate, and extensive necrosis. Immunohistochemistry demonstrated diffuse vimentin positivity with negativity for CK AE1/AE3, CD45, CD20, CD30, CD138, CD117, DOG-1, Melan-A, ERG, smooth-muscle actin, CD21, and HHV-8, with CD3 positivity restricted to reactive lymphocytes-establishing undifferentiated pleomorphic sarcoma by exclusion. Clinically, neutrophilic leukocytosis escalated to >100 × 10⁹/L despite broad-spectrum antibiotics and negative cultures; PET/CT showed intense uptake in the colonic mass and diffuse marrow activity-findings consistent with a cytokine-mediated paraneoplastic leukemoid reaction. Postoperatively, the course was complicated by nosocomial pneumonia and refractory hypoxemia due to sepsis, culminating in early postoperative death from multiorgan failure.

Conclusion/Discussion: This case represents an exceptionally uncommon manifestation of primary colonic UPS in an immunocompromised host, complicated by a paraneoplastic leukemoid reaction-a combination not previously documented. It broadens the recognized clinicopathologic spectrum of colonic sarcomas and reinforces the need for exhaustive immunohistochemical evaluation of undifferentiated colonic masses, particularly in patients with HIV where overlapping infectious and neoplastic processes may obscure diagnosis.

Cross-sectional imaging and gross pathology of the colonic mass
(A) Axial contrast-enhanced CT demonstrating an heterogeneous, predominantly intramural mass at the splenic flexure (11 × 7.8 cm) with central hypodensity compatible with necrosis and increased pericolonic fat stranding, without mechanical obstruction. (B-C) External anterior (B) and posterior (C) views of the resected transverse-colon segment demonstrating distortion by an intramural tumor. (D-E) Cut surfaces corresponding to the pedunculated mucosal nodules. (F-G) Cut surfaces of the intramural mass, showing a tan-white, fleshy tumor with heterogeneous pale areas and central necrosis.
Histopathology and immunophenotype consistent with undifferentiated pleomorphic sarcoma.
(A) Initial biopsy from colonoscopy: immunohistochemistry for vimentin showing diffuse cytoplasmic positivity in tumor cells, supporting mesenchymal lineage. (B) Resection specimen, H&E, low-power panoramic view: sarcoma (five-point star) situated beneath intact colonic mucosa (four-point star). (C) Resection specimen, H&E, high-power (40×): multinucleated tumor cell indicated by an arrow, with a prominent inflammatory infiltrate composed of eosinophils, neutrophils, and monocytes. The complete IHC panel-negative for CK AE1/AE3, CD45, CD20, CD30, CD138, CD117, DOG-1, Melan-A, ERG, smooth-muscle actin, CD21, and HHV-8, with CD3 limited to reactive lymphocytes-established UPS by exclusion.