College of American Pathologists

2012 — January Case of the Month

Posted January 10, 2012


CAP Foundation December 2011 Online Case of the Month

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A 78-year-old man presented with small bowel obstruction. A partial small bowel resection was performed. The 15.0 cm resected portion of bowel contained a 5.5 cm ulcerated, polypoid mass. Tumor cells were immunoreactive for CD138 and kappa light chain (lambda negative).

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2009, case 2, and is plasmacytoma.

Criteria for Diagnosis and Comments:
Sections show a large cell malignant neoplasm diffusely involving the bowel wall with associated mucosal attenuation and ulceration. The tumor cells are large and pleomorphic. Many show distinctive features of plasma cells, including a perinuclear hof and eccentric nuclei. The nuclei exhibit an immature chromatin pattern and prominent nucleoli. Based on the morphology and immunophenotype, the submitting pathologist’s diagnosis was plasmacytoma. Because there is significant overlap between extramedullary plasmacytoma (PC) and large cell lymphoma with plasmablastic/plasmacytic differentiation (LCL-P), this lesion could also be appropriately classified generically as plasmacytic malignant hematolymphoid neoplasm, high grade.

Extramedullary plasmacytomas most commonly involve the head and neck (80%) and are extremely rare in the small bowel, the subject of isolated case reports. Additionally some authors have suggested that many of the reported PC at all sites may in fact be extranodal marginal zone lymphoma with plasmacytic differentiation. Neoplastic plasma cells exhibit a broad morphologic spectrum with the more immature forms showing blast-like nuclear chromatin and prominent nucleoli in contrast to the typical “clock-face” nuclear chromatin of mature plasma cells. Large nuclear size, increased nuclear: cytoplasmic ratio, prominent nuclear pleomorphism with bizarre and multinucleated forms, and eccentric nuclei with prominent nucleoli, as seen in the current case, are common in high grade plasma cell neoplasms.

Overall, non-Hodgkin lymphomas comprise a small subset of gastrointestinal malignancies. However, in the small bowel, lymphomas constitute 30 – 50% of all malignant neoplasms. LCL may arise in the bowel as a de novo lesion or through transformation of a low-grade extranodal marginal zone lymphoma (EMZL-MALT). By convention, when a tumor is composed predominantly or exclusively of large cells, the diagnosis is diffuse large cell lymphoma, not high grade EMZL. De novo intestinal LCL typically occurs in older adults as an exophytic, polypoid or annular infiltrative lesion with deep mural involvement and ulceration of the mucosa, as seen in the current case. These lesions are composed of centroblastic cells with a variable proportion of admixed immunoblasts, plasmablasts, and/or pleomorphic cells with polylobated nuclei; extensive plasmacytic differentiation, as seen in this case, is uncommon.

A significant diagnostic consideration in the small intestine is immunoproliferative small intestinal disease (IPSID). IPSID is a unique form of EMZL-MALT seen in young adult males of Middle East and Mediterranean descent who typically present with chronic diarrhea, malabsorption, and weight loss. Pathologically, IPSID is characterized by exclusive small bowel involvement and demonstrable alpha heavy chain in the cytoplasm of the tumor cells. The earliest form of the disease (Stage A) shows the typical mucosal infiltrate of monocytoid cells and plasma cells with lymphoepithelial lesions. In advanced disease (Stage C) IPSID frequently exhibits features of a high grade malignant neoplasm – including marked nuclear pleomorphism, high mitotic activity and numerous centroblasts and immunoblasts – and may show considerable plasmacytic differentiation. Thus this lesion could quite possibly represent a Stage C IPSID.

The differential diagnosis of plasmacytoma and large cell lymphoma or Stage C IPSID can be addressed with immunohistochemistry, as PC typically shows a CD138 +, kappa or lambda light chain restricted, CD56 +, CD45 dim/–, and PAX5 – phenotype while large B-cell lymphomas are typically CD45 +, CD20 and PAX5 +, CD138, CD56 and cytoplasmic light chain negative; however, there is significant overlap as 10 – 15% of PC will be CD20 + and high grade LCL-P frequently express CD138. CD79a is typically positive in both.

Undifferentiated carcinoma, malignant melanoma, and epithelioid gastrointestinal stromal tumor all enter the differential diagnosis of a high grade large cell malignant neoplasm at this site; however, these tumors would not typically exhibit the prominent plasmacytic features observed in this case. In problematic lesions, an immunohistochemical panel that includes antibodies to high and low molecular weight keratins, S100 protein, “melanoma-specific” antigens (i.e., HMB-45, melan A/MART1, microphthalmia transcription factor, tyrosinase), CD117 and CD34 should provide a definitive classification in most cases. CD117 must be used with caution in this setting as CD117 immunoreactivity is observed in a significant minority of plasma cell neoplasms and in melanoma. Additionally, as epithelial membrane antigen (EMA) is characteristically expressed in neoplastic plasma cells, it would not be a reliable marker of epithelial differentiation in this setting.

In summary, assuming that a comprehensive immunohistochemical panel as defined above yielded only immunoreactivity for CD138 and kappa light chain, this high grade malignant neoplasm is best classified as “plasmacytic malignant hematolymphoid neoplasm, high grade” with a discussion in the diagnostic report of the differential diagnosis (i.e., plasmacytic/plasmablastic large cell lymphoma, IPSID with transformation, plasmacytoma) and a recommendation for correlation with clinical findings and laboratory studies to include serum and urine protein electrophoresis, quantitative immunoglobulins, immunofixation electrophoresis of serum and urine, and bone marrow examination.

Supplementary Questions: For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Immunoproliferative small intestinal disease typically occurs in asymptomatic, older males. A. True
B. False
2. Large B-cell lymphoma and plasmacytoma can be reliably distinguished by the use of CD138, CD20, and CD79a. A. True
B. False
3. CD117 expression may be seen in malignant melanoma and plasma cell neoplasms as well as gastrointestinal stromal tumors. A. True
B. False


  1. Dilworth HP. Neoplasms of the small intestine. In: Iacobuzio-Donahue CA, Montgomery E, eds. Gastrointestinal and Liver Pathology. Philadelphia, PA: Churchill Livingstone; 2005:174-203.
  2. Ferry JA. Lymphoid tumors of the GI tract. In: Odze RD, Goldblum JR, Crawford JM, eds. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. Philadelphia, PA: Saunders; 2004:523-551.
  3. Gascoyne RD, Muller-Hermelink HK, Chott A, Wotherspoon A. B-cell lymphoma of the small intestine. In: Hamilton SR, Aaltonen LA, eds. The WHO Classification of Tumors of the Digestive Tract. Lyon, France: IARC Press; 2000:83-86.
  4. Lin P. Plasma cell disorders. In: Hsi, ED. ed. Hematopathology. New York, NY: Churchill Livingstone; 2007:573-590.

Richard W. Brown, MD FCAP
Surgical Pathology Committee
Memorial Hermann Healthcare System
Houston, TX