Sarcomatoid (Undifferentiated) Carcinoma Masquerading as an Epithelioid Mesenchymal Neoplasm in the Colon: A Histopathological and Immunohistochemical Diagnostic Pitfall.
Year: 2026
Type: article
Study design: Case Report
Abstract: Article Type: Case Report / Scientific Pre-print Target Platform: Zenodo Repository Keywords: Sarcomatoid Carcinoma, Undifferentiated Carcinoma, Colonic Metastasis, Diagnostic Pitfall, Hemangiopericytomatous Pattern, Immunohistochemistry. Abstract Sarcomatoid (undifferentiated) carcinoma is an aggressive, highly malignant neoplasm characterized by epithelial loss of differentiation and mesenchymal transdifferentiation. Presentation as a colonic mass in the absence of a known mucosal primary or clinical antecedent represents a formidable diagnostic challenge. We report the case of a 45-year-old female undergoing surgery for symptomatic uterine leiomyomas, during which an incidental left upper quadrant colonic mass was discovered. Hematoxylin and Eosin (H&E) evaluation of the colonic lesion revealed a dense epithelioid and spindle cell proliferation displaying trabecular architecture, stromal hyalinization, and a striking hemangiopericytoma-like vascular pattern, mimicking a gastrointestinal stromal tumor (GIST), solitary fibrous tumor (SFT), or primary epithelioid sarcoma of the colon. Extended immunohistochemical profiling unmasked reactivity for cytokeratins (CK AE1/AE3 with a perinuclear dot-like pattern, focal CK7+) and estrogen receptors (ER+ partial), while showing complete negativity for enteric markers (CK20-, CDX2-), pure mesenchymal markers (CD34-, DOG1-, CD117-), and neuroendocrine markers. The definitive diagnosis of Sarcomatoid (Undifferentiated) Carcinoma was established, strongly pointing toward an occult gynecologic/müllerian derivation. This case underscores the imperative role of immunohistochemistry in preventing diagnostic misclassification of ambiguous intestinal tumors. 1. Introduction Sarcomatoid carcinoma is a rare biphasic or transdifferentiated malignant tumor containing epithelial elements combined with or transformed into a sarcomatous phenotype. Although it can arise across various organ systems (including the lung, kidney, and female genital tract), secondary or primary involvement of the colonic wall remains exceptionally rare. Morphologically, these neoplasms frequently lack classic epithelial features such as overt tubuloglandular differentiation on routine H&E staining. Instead, they adopt solid sheet-like growths, trabecular arrangements, plasmacytoid/epithelioid cytology, and a prominent vascular network that mimics perivascular tumors or primary mesenchymomas. We present a classic diagnostic pitfall of a colonic sarcomatoid carcinoma whose initial histologic appearance strongly simulated an intermediate-to-high grade epithelioid or vascular mesenchymal neoplasm. 2. Case Presentation 2.1 Clinical History and Intraoperative Findings A 45-year-old female (Gravida 1, Parity 0, 3-month amenorrhea) presented with symptomatic uterine fibroids. Exploratory laparotomy revealed a multifibroid uterus, extensive pelvic adhesions, and a large, partially necrotic left upper quadrant colonic mass. Total abdominal hysterectomy with bilateral salpingectomy (Specimen A) and resection/biopsy of the colonic mass (Specimen B) were performed. 2.2 Histopathological Findings (H&E) Specimen A (Uterus and Adnexa): Sections demonstrated intramural and subserosal smooth muscle tumors composed of intersecting fascicles of benign spindle cells without cytologic atypia or necrosis, consistent with uterine leiomyomas, along with endometrial hyperplasia without atypia. The cervix and fallopian tubes showed no significant abnormalities. Specimen B (Colonic Mass): Tissue fragments showed a highly cellular neoplasm composed of epithelioid and focal spindle cells arranged in solid sheets, trabecular cords, and short intersecting fascicles. A prominent hemangiopericytoma-like vascular network composed of thin-walled, branching ectatic vessels was evident throughout. Tumor cells exhibited round-to-oval nuclei, vesicular chromatin, small nucleoli, and moderate eosinophilic cytoplasm. No overt glandular differentiation was appreciated on routine H&E staining. 2.3 Immunohistochemical (IHC) Analysis To resolve the differential diagnosis between carcinoma, GIST, epithelioid sarcoma, and neuroendocrine tumor, an extensive immunohistochemical panel was conducted. Results are summarized in Table 1. Table 1: Immunohistochemical Profile of the Colonic Mass (Specimen B) Marker Category Marker Staining Result Diagnostic Interpretation Epithelial Lineage CK AE1/AE3 Positive (Dot-like pattern) Confirms epithelial derivation / Carcinoma CK7 Positive (Focal, strong) Supports non-enteric epithelial differentiation Hormonal Receptor ER (Estrogen Receptor) Positive (Weak, partial) Suggests gynecologic / müllerian origin Myoepithelial / Mesenchymal SMA (Smooth Muscle Actin) Positive Highlights sarcomatoid transdifferentiation GI / Enteric CK20 / CDX2 Negative Rules out classic colorectal adenocarcinoma GIST / Perivascular CD34 / DOG1 / CD117 Negative Excludes Gastrointestinal Stromal Tumor (GIST) Neuroendocrine Synaptophysin / Chromogranin Negative Excludes neuroendocrine carcinoma Mesenchymal / Specific Desmin / WT-1 / TLE1 / PAX-8 Negative Excludes specific sarcomas & serous carcinoma Melanocytic / Squamous Melan A / p63 / ALK1 Negative Excludes melanoma and squamous carcinoma Chromatin Remodeling INI-1 (SMARCB1) Retained Excludes INI-1 deficient / rhabdoid tumors 2.4 Final Diagnosis Sarcomatoid (Undifferentiated) Carcinoma, with immunophenotypic features strongly favoring a secondary/metastatic origin from the gynecologic tract. 3. Discussion The diagnostic approach to epithelioid and spindle cell lesions of the gastrointestinal tract is notoriously challenging. In this case, the combination of trabecular architecture, eosinophilic cytoplasm, and a prominent staghorn/hemangiopericytomatous vascular pattern on H&E closely mimicked several entities: Epithelioid or Undifferentiated GIST: Categorically excluded by negative staining for CD117, DOG1, and CD34. Solitary Fibrous Tumor (SFT) or Angiosarcoma: Excluded by negative CD34 staining (which highlighted only normal vessels). Primary Colorectal Adenocarcinoma: The absence of CK20 and CDX2 effectively ruled out classic enteric adenocarcinoma. Reactivity for CK AE1/AE3 featuring a perinuclear dot-like pattern is a classic hallmark of poorly differentiated carcinomas undergoing sarcomatoid change, where cytokeratin filaments aggregate perinuclearly. Coupled with partial positivity for Estrogen Receptor (ER), these findings indicate that the colonic mass represents a metastatic or directly invasive deposit from an high-grade gynecologic/müllerian carcinoma. 4. Conclusions Hematoxylin and Eosin staining alone can be deceptive in atypical colonic masses, frequently mimicking primary mesenchymal or perivascular neoplasms due to reactive vascular backbones. Sarcomatoid carcinoma must remain in the differential diagnosis of any undifferentiated epithelioid or spindle cell tumor involving the intestinal wall. Broad-spectrum cytokeratins (CK AE1/AE3) and hormone receptors (ER) are vital for unmasking epithelial lineage and identifying potential primary sites in undifferentiated malignancies. References Viswanathan AN, Deavers MT, Euscher ED, et al. Sarcomatoid carcinoma of the female genital tract: a clinicopathologic study. Am J Surg Pathol. 2008;32(7):1011-1021. Perchick BG, Erlandson RA, Huvos AG. Sarcomatoid carcinoma: a clinicopathologic and immunohistochemical study. Am J Surg Pathol. 1991;15(10):923-934. Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, and differential diagnosis. Arch Pathol Lab Med. 2006;130(10):1466-1478. Wick MR. Immunohistochemistry in the diagnosis of epithelioid and sarcomatoid neoplasms. Semin Diagn Pathol. 2014;31(1):57-68.
Author: Milanés Sánchez, José Luis
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7201875346