A 58-year-old male with no past medical history presenting to the emergency department with 2-month history of increasingly severe generalized abdominal pain accompanied by intermittent “stabbing sensations” with or without eating. The patient states the pain is so severe he has been unable to sleep and over the past few weeks he has noted dark stools, intermittent fevers, nights sweats, and chills. He reports an approximately 43-pound weight loss over the past few months some of which he attributes to intentional weight loss. The patient reports vomiting after eating if he lays down and only able to eat or drink while standing. Social history includes a 10 pack-year smoking history with cessation 6 months ago. He denies heavy alcohol use or history of pancreatitis.
Computed tomography with contrast of the abdomen was significant for a 10.0 x 10.0 x 7.0 cm hypoattenuating pancreatic head mass with double duct sign and encasement of the surrounding vessels. Multiple, scattered hypodense lesions were noted throughout the right hepatic lobe concerning for metastatic disease. Endoscopic findings showed an ulcerated, infiltrating mass in the duodenal bulb. Images of the duodenal biopsies are shown below.
Figure 1. H&E stain
Figure 2. H&E stain
Figure 3. H&E stain
Figure 4. H&E stain
Figure 5. CK7
Figure 6. CK5/6
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Please Select Your Diagnosis in the Poll, Then See the Answer and the Discussion in the Links Below
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Answer: Undifferentiated carcinoma, anaplastic type
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Microscopic appearance: This is a high-grade malignancy revealing predominantly diffuse sheet-like growth pattern, without overt glandular differentiation, with hemorrhage and necrosis. It is composed of atypical epithelioid and spindle-shaped cells intermixed with pleomorphic, multinucleated cells with bizarre nuclei.
Immunohistochemistry: These cells are positive for pancytokeratin, CK7, Cam 5.2, EMA (focal), CK5/6, and p63 immunohistochemical stains.
Final diagnosis: Undifferentiated carcinoma, anaplastic type
Discussion: Undifferentiated carcinoma is one of the histologic subtypes of pancreatic ductal adenocarcinoma. Three morphological patterns of this subtype have been recognized by the current (5th edition) WHO.
Anaplastic type undifferentiated carcinoma is characterized by pleomorphic mononuclear cells admixed with bizarre-appearing giant cells with eosinophilic cytoplasm. At least 80% of the neoplasm consists of solid sheets of cells lacking gland formation and showing markedly pleomorphic nuclei. There is usually a neutrophilic inflammatory infiltrate. Keratin expression is typically present.
Sarcomatoid type undifferentiated carcinoma is characterized by spindle-shaped cells and may contain admixed heterologous elements of bone and cartilage. At least 80% of the neoplasm displays spindle cell features,with or without heterologous differentiation. A potential pitfall exists if only heterologous elements are sampled in a limited biopsy specimen, suggesting a soft tissue tumor, chondrosarcoma, or osteosarcoma. Sarcomatoid undifferentiated carcinomas with rhabdoid cells have also been described. Loss of nuclear expression of SMARC1 (INI1) is characteristic in these rare cases.
Carcinosarcoma reveals components with obvious epithelial morphology and sarcomatous elements, with or without heterologous differentiation, and requires each component to constitute 30% of the neoplasm.
Differential diagnosis:
Metastatic Melanoma to the small intestine is well documented and may histologically mimic undifferentiated carcinoma, anaplastic type. Morphologically, melanoma may show large pleomorphic cells with eosinophilic cytoplasm and macronuclei admixed with spindle or epithelioid cells. A panel of routine melanoma immunohistochemistry including Melan-A, HMB45, S100, and SOX10 is highly sensitive for metastatic melanoma.
Undifferentiated carcinoma with osteoclast-like giant cells, another histologic subtype of pancreatic ductal adenocarcinoma, is composed of neoplastic mononuclear cells, mononuclear histiocytic cells, and non-neoplastic osteoclast-like multinucleated giant cells. Heterologous elements such as bone and cartilage may be present.
Dedifferentiated GISTs are composed atypical spindle-shaped, epithelioid cells, and may contain large pleomorphic cells. These neoplasms are exceptionally rare and more frequently observed in patients with a history of GIST following long term tyrosine kinase inhibitor therapy. Notably, dedifferentiation typically includes a loss of KIT immunoreactivity.
Adenosquamous carcinoma of the pancreas comprises approximately 2% of pancreatic exocrine cancers. Squamous and glandular components may be intermixed or distinctly separate. The squamous component must comprise at least 30% of the tumor and will stain with p63, CK5/6, and high molecular weight cytokeratin.
References:
Gulati A, Kaushal V, Gupta N. Undifferentiated carcinoma of pancreas with osteoclast-like giant cells mimicking a pseudopancreatic cyst. J Cancer Res Ther. 2015;11(4):1046.
Hoorens A, Prenzel K, Lemoine NR, Klöppel G. Undifferentiated carcinoma of the pancreas: analysis of intermediate filament profile and Ki-ras mutations provides evidence of a ductal origin. J Pathol. 1998;185(1):53-60.
Manduch M, Dexter DF, Jalink DW, Vanner SJ, Hurlbut DJ. Undifferentiated pancreatic carcinoma with osteoclast-like giant cells: report of a case with osteochondroid differentiation. Pathol Res Pract. 2009;205(5):353-9.
Yonemasu H, Takashima M, Nishiyama KI et al. Phenotypical characteristics of undifferentiated carcinoma of the pancreas: a comparison with pancreatic ductal adenocarcinoma and relevance of E-cadherin, alpha catenin and beta catenin expression. Oncol Rep. 2001;8(4):745-52.
Patil DT, Rubin BP. Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Pathol Lab Med. 2011;135(10):1298-310.
Odze RD, Goldblum JR. Odze and Goldblum surgical pathology of the GI tract, liver, biliary tract, and pancreas. Third edition. ed. Philadelphia, PA: Saunders/Elsevier; 2015:xix, 1612 pages.
WHO Classification of Tumours Editorial Board, World Health Organization., International Agency for Research on Cancer. Digestive system tumours. 5th ed. Lyon: IARC Press; 2019
Choi JJ, Sinada-Bottros L, Maker AV, Weisenberg E. Dedifferentiated gastrointestinal stromal tumor arising de novo from the small intestine. Pathol Res Pract. 2014;210(4):264-6.
Oka K, Inoue K, Sugino S et al. Anaplastic carcinoma of the pancreas diagnosed by endoscopic ultrasound-guided fine-needle aspiration: a case report and review of the literature. J Med Case Rep. 2018;12(1):152.
Sano M, Homma T, Hayashi E, Noda H, Amano Y, Tsujimura R, Yamada T, Quattrochi B, Nemoto N.Clinicopathological characteristics of anaplastic carcinoma of the pancreas with rhabdoid features. Virchows Arch. 2014;465(5):531-8.
Muraki T, ReidMD, Basturk O, Jang KT, Bedolla G, Bagci P, Mittal P, Memis B, Katabi N, Bandyopadhyay S, Sarmiento JM, Krasinskas A, Klimstra DS, Adsay Undifferentiated Carcinoma with Osteoclastic Giant Cells of the Pancreas: Clinicopathologic Analysis of 38 Cases Highlights a More Protracted Clinical Course Than Currently Appreciated. Am J Surg Pathol. 2016;40(9):1203-16.
Agaimy A, Haller F, Frohnauer J, Schaefer IM, Ströbel P, Hartmann A, Stoehr R, Klöppel G. Pancreatic undifferentiated rhabdoid carcinoma: KRAS alterations and SMARCB1 expression status define two subtypes.Mod Pathol. 2015;28(2):248-60.
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Case contributed by:
Adam L. Booth, MD Anatomic and Clinical Pathology Resident, PGY-4 University of Texas Medical Branch, Galveston, TX
Nicole D. Riddle, MD Assistant Professor, Associate Residency Program Director University of South Florida, Tampa, FL
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