|Year : 2021 | Volume
| Issue : 2 | Page : 89-91
Idiopathic polyclonal plasmacytosis presenting as fever of unknown origin
Vivek Pal Singh, Ashutosh Garg
Department of Internal Medicine, BLK Super Speciality Hospital, New Delhi, India
|Date of Submission||19-Oct-2020|
|Date of Acceptance||28-Oct-2020|
|Date of Web Publication||22-Mar-2021|
Dr. Vivek Pal Singh
Department of Internal Medicine, BLK Super Speciality Hospital, Pusa Road, New Delhi - 110 005
Source of Support: None, Conflict of Interest: None
An elderly male, after being flagged to have fever of unknown origin, was found to have plasmacytosis on bone marrow examination. On immunophenotyping, the proliferation was confirmed as polyclonal. No associated underlying condition such as infection or connective tissue disease was found. The importance of polyclonal plasmacytosis is discussed vis-a-vis the usual knee jerk reaction to diagnose multiple myeloma.
Keywords: Fever of unknown origin, plasmacytosis, polyclonal
|How to cite this article:|
Singh VP, Garg A. Idiopathic polyclonal plasmacytosis presenting as fever of unknown origin. Indian J Med Spec 2021;12:89-91
|How to cite this URL:|
Singh VP, Garg A. Idiopathic polyclonal plasmacytosis presenting as fever of unknown origin. Indian J Med Spec [serial online] 2021 [cited 2021 Nov 29];12:89-91. Available from: http://www.ijms.in/text.asp?2021/12/2/89/311694
| Introduction|| |
In India, tuberculosis is the most common cause of fever of unknown origin (FUO). However, after infections and connective tissue diseases, lymphoproliferative disorders occupy primacy., Monoclonal plasma cell proliferation (PCP) manifesting as FUO leads us to plasma cell malignancy. These cells secrete the monoclonal set of immunoglobulins; however, an entity called “reactive PCP” exists. It exhibits polyclonality and usually underlies a connective tissue disease or an infection. In patients, FUO is a perplexing case, more so when PCP is polyclonal. What follows is a case report of an elderly Indian male presenting with FUO who was found to have idiopathic reactive PCP.
| Case Report|| |
We present the case of a 67-year-old Indian male who presented to our hospital with 1½ month history of fever. There was no organ system(s) localizing clinical features in history. There was no associated skin rash, joint pain, weight loss, or loss of appetite. He was not suffering from a chronic disease nor a history of previous hospitalization, blood transfusion, or surgery. There was no family history of tuberculosis, autoimmune disease, or malignancy. He did not abuse any illicit substance or use any recreational drugs or herbal medicines on a chronic basis. On examination, he was febrile with an oral temperature of 101°F. The rest of the physical examination was unremarkable. His initial laboratory tests demonstrated moderate microcytic hypochromic anemia with thrombocytosis, leukocytosis, and raised inflammatory markers [Table 1]. Rouleaux formation was observed in peripheral blood film [Figure 1]a. On ultrasonography, he had an enlarged liver, gallbladder sludge, and mild fullness of the left pelvicalyceal system. Blood and urine cultures were sterile. Mantoux test showed anergy. Human immunodeficiency virus (HIV) 1 and 2 antibodies were negative. Urine for TB-PCR was also negative. Endocarditis and prothrombotic states were ruled out. Other relevant investigations pertaining to FUO are enumerated in [Table 2]. Contrast-enhanced computed tomography scan of the thorax and abdomen showed lobulated hypodense lesion involving the posterior wall of the stomach near the gastroesophageal junction. Upper gastrointestinal endoscopy with endoscopic ultrasound was done which was noncontributory. Sinuses on imaging were normal. Dental examination was unremarkable. An increase in plasma cells for age was seen both in bone marrow aspirate and biopsy [Figure 1]b and [Figure 1]c and was further confirmed by clusters of differentiation (CD) 138 staining [Figure 1]d. Flow cytometry also confirmed plasmocytsis which was polyclonal [Figure 1]e and [Figure 1]f. Karyotyping revealed normal chromosomes. Thus, a diagnosis of idiopathic polyclonal plasmacytosis was made. The patient was given a course of pulse IV steroids. Fever and his subjective feeling of illness subsided over a period of time. He was switched to oral steroids and discharged on the same.
|Figure 1: (a) Peripheral smear (×10) showing increase in rouleaux formation; (b) Bone marrow aspirate (×40) showing increase in plasma cells (arrow) with binucleate forms (dotted arrows); (c) Bone marrow biopsy (×20) showing increased plasma cells confirmed by CD138; (d and e) Flow cytometry dot plot showing CD38-CD138 gating to select plasma cells (red). Granulocytes (pink), monocytes (green), lymphocytes (dark blue), erythroid cells (light blue); (f) Dot plot showing plasma cells (red) to be polyclonal. CD: Clusters of differentiation|
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Plasma cells are responsible for producing antibodies. As such, it is usual to find proportionate proliferation in states of infections, other inflammatory conditions, and malignancies. It is associated with concomitant hypergammaglobulinemia. Each plasma cell can produce only one configuration of immunoglobulin, and the inciting antigen results in corresponding proliferation. However, for a given bacteria or virus, there are numerous antigens. Therefore, a variety of immunoglobulins are produced, with each type being from a specific plasma cell precursor. However, in plasma cell malignancy – the prototype of which is multiple myeloma – there is a monoclonal proliferation of plasma cells and a single type of immunoglobulin is produced. Immunoelectrophoresis is now a commonly available test that helps us to characterize the immunoglobulins' pattern and shows the result of plasma cell malignancy as the “M” band or monoclonal band.
Reactive plasma cells, in contrast, exhibit polyclonality and thus show a multi-immunoglobulin pattern on immunoelectrophoresis. As is evident from the prefix “reactive,” it is usually secondary to an underlying factor. Polyclonal PCP, without an antecedent trigger, is a rare phenomenon. In the setting in which PCP does present, it is usually in association with connective tissue disorders and infections., Streptococcal sepsis, Pseudomonas aeruginosa sepsis, infectious mononucleosis, HIV infection, and dengue fever are known infectious triggers.,, Streptokinase therapy has also been linked with PCP., The clinical features of said underlying diseases predominate and PCP subsides with their treatment. SPEP is a commonly available test to characterize immunoglobulins and clonality can be verified with it. However, plasma cells may not exhibit proliferation that can be picked up on peripheral smear. In such a case, bone marrow and lymph node biopsies might ultimately point toward the diagnosis. On tissue biopsy, cellular atypia in the form of polychromasia, multinucleation, prominent nucleoli, and marked variation in cell size and shape is hallmark of neoplasm. In multiple myeloma, usually, the population of such plasma cells is above 30% of all cellularity. This is sine qua non for a malignant process; however, depending on the biopsy extracted, relatively benign cells may seem to predominate. This therefore necessitates further typification. Other than immunoelectrophoresis, immunophenotyping – usually by flow cytometry – is a cell-specific method to typify the cells in circulation and to distinguish reactive cells from malignant cells. This is accomplished by identifying the CD markers on cells. While malignant cells highly express CD138 and CD156 and are negative for CD19, reactive plasma cells often express CD38 and CD19 and are negative for CD56. Karyotyping of plasma cells can aid to confirm the presence of aberrant chromosomal structure underlying the defect.
If polyclonality comes to the fore, then the diagnosis of a malignancy is refuted. It is therefore imperative to find potential triggers for this (assumed) reactivity. Through this case, we endeavor to highlight that plasma cell neoplasm must not be diagnosed (or ruled out) without establishing clonality. Recognized infections and connective tissue diseases must be looked for. The literature relating to potential primary pathology is sparse but is growing because of eagerness to find it and and due to easy availability of advanced diagnostic laboratories.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
The authors would like to thank Dr. Anil Handoo, Director, Laboratory Services, BLK Super Speciality Hospital, for the help rendered.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]