November 2014

A 65-year-old-female that presented with a chief complaint of fatigue and back pain

Ryan Okal M.D., Flavia Rosado M.D. and Jeffrey Vos M.D.

Clinical History

The patient is a 65-year-old-female that presented with a chief complaint of fatigue and back pain. During the physical examination, she was found to have palpable inguinal lymphadenopathy, bilaterally. Her past medical history was significant for poorly differentiated squamous cell carcinoma diagnosed 16 months prior to this visit. At that time, laryngoscopy demonstrated an exophytic lesion involving the left and right sides of the vallecula, which was biopsied and demonstrated poorly differentiated squamous cell carcinoma. Positron emission tomography / computerized tomograph (PET/CT) scan performed as part of patient’s initial staging procedure showed positive bilateral lymph nodes within level II of the neck and involvement of the epiglottis, consistent clinically with Stage 4 disease (cT4a). Chemoradiation was initiated and follow-up PET/CT showed no residual active disease at three months.

Approximately one year following diagnosis of laryngeal squamous cell carcinoma, the patient developed mild thrombocytopenia and macrocytic anemia. Bone marrow biopsy at that time showed a normocellular marrow with no evidence of metastatic disease, high-grade myeloid neoplasm, or lymphoma. It was, however, significant for megaloblastic anemia, ring sideroblasts, and erythroid hyperplasia. A low-grade myelodysplastic syndrome could not be excluded as other conditions (autoimmune, inflammatory, or nutritional deficiencies) could also have explained these findings. 

The patient’s current complaints of fatigue and back pain, in conjunction with the finding of lymphadenopathy and past medical history of squamous cell carcinoma strongly suggested the possibility of recurrent metastatic disease. Subsequently, a PET/CT scan was performed that showed hypermetabolic activity within multiple lymph nodes in the mediastinum, retroperitoneum, and inguinal areas. No lytic lesions were identified. The palpable inguinal lymph node on the right side was excised for pathologic evaluation. 

Gross Description

Laboratory Testing

  • WBC: 3.6 with absolute lymphopenia
  • Hemoglobin: 8.6
  • Platelet count: 105
  • SPEP: Monodispersed zone without hypogammoglobinemia 
  • IFE: Small IgG Kappa monoclonal protein

Microscopic examination

Sections of the lymph node revealed diffuse architectural effacement (image 1). 

The node was effaced by a spectrum of cells including mature plasma cells, small lymphocytes with irregular nuclei, immunoblasts, and centroblast-like cells (image 2). Numerous mitotic figures and occasional apoptotic cells were identified (image 3).

Immunohistochemical stains and in-situ hybridization studies were performed to further characterize the process. The immunoblasts and plasma cells were kappa light chain-restricted (image 4 and image 5) and further expressed multiple myeloma 1 (MUM-1), CD43, CD45, and epithelial membrane antigen (EMA). There was variable expression of CD30, CD79a, and CD138 (image 6). The cells were negative for activin receptor-like kinase-1 (alk-1), B-cell lymphoma-6 (bcl-6), CD20, CD5, CD10, CD3, CD4, CD7, CD8, and paired box 5 (PAX 5). The cells were Epstein Barr virus encoded RNA (EBER) negative and demonstrated a Ki-67 proliferation rate of approximately 80%.

Image 1: Hematoxylin and eosin stain of lymph node with diffuse architectural effacement (10x).
Image 2: Hematoxylin and eosin stain of lymph node with a spectrum of malignant lymphoid cells including many plasmacytoid forms (40x).
Image 3: Hematoxylin and eosin stain of lymph node with apoptotic bodies and mitoses (60x).
Image 4: Kappa in situ hybridization of lymph node (20x).
Image 5: Lambda in situ hybridization of lymph node (20x).
Image 6: CD138 immunohistochemical stain of lymph node (20x).

Diagnosis

Based on the clinical history, histologic appearance, immunohistochemical and in-situ hybridization studies, this process is best characterized as which of the following ?

Answer

Please select an answer above.

Discussion

Plasmablastic lymphoma (PBL) is an uncommon malignant neoplastic proliferation of cells with a spectrum of morphologic features ranging from B-immunoblasts to cells with a mature plasmacytic appearance. Despite the morphologic variability, all of the neoplastic cells have an immunophenotype consistent with plasma cell differentiation. The tumor is typically high-grade with numerous mitotic figures, apoptotic bodies, and Ki-67 proliferation index frequently over 90%. 

Although PBL is uncommon overall, it is more frequently seen in immunosuppressed patients (HIV, autoimmune suppression therapy, post-transplant, etc.). Cases that are more monomorphic and plasmablastic tend to occur in the oral / nasal cavity and usually occur in the setting of HIV infection. In contrast, those cases that more closely resemble mature plasma cells often occur in non-oral extranodal sites and in lymph nodes and are not HIV-associated.

The immunophenotypic profile of PBL supports the name. The neoplastic cells tend to be immunoreactive for CD138 and CD38, regardless of the morphologic appearance of the cells. Virtually all cases are MUM-1 positive. CD45 has variable expression ranging from weak to negative. Most cases are weak or negative for B-cell antigens including CD20 and PAX-5. Interestingly, nearly 100% of cases occurring within the oral / nasal areas are EBER positive, but when including all locations, the expression frequency drops to 60-75%. EMA and CD30 are also commonly expressed. Alk-1, bcl-6, cyclin D1, and HHV-8 are usually negative. Of note, the most common cytogenetic alteration identified involves MYC in approximately 50% of cases.

Many of the typical features of plasmablastic lymphoma are present within this case. The present case had numerous mitotic figures, apoptotic cells, and a high Ki-67 of approximately 80%. The neoplastic cells expressed plasmacytic markers, lacked the B-cell antigens CD20 and PAX-5, and expressed EMA. They were also negative for alk-1 and bcl-6. The malignant cells were negative for EBER, which given the lack of an HIV history and non-oral / nasal location, is not unexpected for this clinical profile (i.e., as many as 40% of cases are EBER negative with this history and presentation). Most cases of PBL are only weakly CD45 positive or even negative. The cells were strongly positive for CD45 in this case, which was atypical. However, as many as 56% of cases of non-oral PBL can have positive staining for CD45. In regards to cytogenetics, no MYC rearrangement was detected in this case.

The diagnosis of PBL may be challenging due to morphologic variability, the initially broad differential diagnosis, and the rarity of the lesion. In this case, an extensive immunohistochemical panel was performed to exclude other lymphomas and confirm the diagnosis. The prognosis of PBL is quite poor. The disease course is aggressive and most patients die within the first year of diagnosis. 

References

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