Indian Journal of Pathology and Microbiology

LETTERS TO EDITOR
Year
: 2020  |  Volume : 63  |  Issue : 1  |  Page : 151--153

Myeloma co-existing with prostatic carcinoma: Clues from a “non-coagulable” prothrombin time


Jasmita Dass1, Suchi Mittal1, Nitin Gupta2, Jyoti Kotwal2,  
1 Department of Hematology, Sir Ganga Ram Hospital, New Delhi, India
2 Department of 1Clinical Hematology, Sir Ganga Ram Hospital, New Delhi, India

Correspondence Address:
Jasmita Dass
Department of Hematology, Sir Ganga Ram Hospital, New Delhi
India




How to cite this article:
Dass J, Mittal S, Gupta N, Kotwal J. Myeloma co-existing with prostatic carcinoma: Clues from a “non-coagulable” prothrombin time.Indian J Pathol Microbiol 2020;63:151-153


How to cite this URL:
Dass J, Mittal S, Gupta N, Kotwal J. Myeloma co-existing with prostatic carcinoma: Clues from a “non-coagulable” prothrombin time. Indian J Pathol Microbiol [serial online] 2020 [cited 2022 May 26 ];63:151-153
Available from: https://www.ijpmonline.org/text.asp?2020/63/1/151/277375


Full Text



Editor,

A 70-year-old male patient's citrated blood sample sent for prothrombin time (PT) was run on an ACL TOP 500 automated analyzer (Instrumentation Laboratories, Werfen, USA) and was reported as “failed” by the instrument. The instrument measures PT till 320 s and therefore the value was taken as >320 s. No clots or hyperbilirubinemia were detected. As per the laboratory protocol, a manual PT was performed and the value was 24.0 s. The PT was completely corrected on 1:1 mixing with normal plasma. Activated partial thromboplastin time (APTT) was within the reference range (35.0 s). His fibrinogen level was 1.9 g/dL. A corresponding serum sample sent to biochemistry laboratory showed a coagulum.

A paraprotein was suspected in view of the prolonged PT with lack of yellowness of plasma and the serum showing a coagulum. The clinician was contacted and the patient's history was reviewed. He was a case of prostatic adenocarcinoma (Gleason score – 4 + 5 = 9) diagnosed 4 months back. He reported excess bleeding after prostatic biopsy for which fresh frozen plasma and packed red blood cells were given. Bone scan done at that time had revealed multiple lytic lesions suggesting skeletal metastases. With this background, further tests were done. Hemogram showed hemoglobin 6.9 g/dL, total leucocyte count 2.21 × 109/L, and platelet count 153 × 109/L. Bone marrow aspiration (BMA) revealed aggregates of large malignant cells and 12% plasma cells. The biopsy (BMBx) showed extensive carcinomatous metastases (diffusely positive for pan-cytokeratin and prostate-specific antigen, with CD138 expression which was weak in most areas but also showed intense positivity in other areas) and focal osteomyelosclerosis together with plasma cell aggregates [Figure 1]. There were focal small collections of intensely CD138-positive plasma cells showing λ-light chain restriction [Figure 2]. Thus, the marrow findings were consistent with synchronous plasma cell myeloma and metastatic prostatic carcinoma (PCa). Serum protein electrophoresis (SPE) showed an M-band of 4.37 g/dL which was typed as IgAλ on immunofixation (IFE).{Figure 1}{Figure 2}

The patient was started on injection zoledronic acid for skeletal metastasis and anti-androgen therapy in the form of triptorelin 12.5 mg for carcinoma prostate. He refused therapy at the time of diagnosis of myeloma and subsequently died.

 Discussion



Synchronicity has been reported between multiple myeloma (MM) and solid tumors but their association is not well established. The co-existence of MM with secondary hematologic malignancy was 0.7% and with secondary hematologic malignancy was 1.9% in a study by Kyle et al.[1]

It is unusual to find PCa metastasizing to bone marrow with synchronous MM. In the literature only a few cases have been reported depicting this phenomenon. There is no evidence to support an association between these disorders but there are significant similarities in the micro-environment in both PCa and myeloma such as interleukin-6 and insulin-like growth factor-1 (IGF-1).[2],[3],[4] When paraproteinemia is seen in association with solid tumors, it is important to document the neoplastic nature of the plasma cells and assess for other features of symptomatic myeloma. Skeletal manifestations, anemia, and hypercalcemia can be seen in both metastases and myeloma, but the presence of renal failure would favor the latter. The treatment in such cases is usually directed toward the more advanced malignancy.

Distinguishing overt symptomatic myeloma from smoldering myeloma can be challenging in cases such as ours. While the 12% λ-restricted bone marrow plasma cells and the IFE findings confirmed the presence of a neoplastic plasma cell clone that had grown beyond monoclonal gammopathy of undetermined significance, the mandatory clinical features (anemia, bony lesions) were difficult to interpret as the patient had another plausible explanation for those findings (active metastatic carcinoma prostate).

MM patients with high titer serum paraproteins can manifest hemostatic abnormalities, thus predisposing them to hemorrhage and rarely, thrombotic complications.[5] The pathophysiology of hemorrhage in MM involves various factors like abnormal immunoglobulins that interfere with the function and metabolism of coagulation factors, a paraprotein with anticoagulant activity, thrombocytopenia due to massive marrow infiltration, and acquired factor X deficiency due to myeloma-associated amyloidosis.[6] Coagulopathy is noted in IgG and IgA myeloma, but less frequently in patients with light chain disease indicating that intact plasma paraproteins contribute to the development of coagulopathy.[7]

On the other hand, patients with PCa are known to have disseminated intravascular coagulation that ranges from asymptomatic laboratory manifestations like a prolonged PT or an APTT, elevated d-dimer or reduced fibrinogen, or may lead to thrombosis or bleeding.[8] The prolonged PT in our patient was likely on an account of non-overt disseminated intravascular coagulation (DIC) but this was wrongly reported as “failed” by a photo-optical coagulometer. This finding was a clue to the diagnosis of a synchronous myeloma in a patient of PCa.

It was also interesting to note that the epithelial component also showed dim CD138 in a few cells which can be explained by the fact that CD138 is plasma cell specific only in the context of hematopoietic tissue. A wide variety of solid tumors may also show CD138 reactivity and therefore a positive CD138 is not an evidence enough of a plasma cell myeloma.[9],[10] It has to be supplemented with immunostaining for light chains to demonstrate clonality of PCs.[9] In fact in PCa, there are reports of higher recurrence rates after radical prostatectomy if the tumor was CD138 positive as it may help stabilize tumor initiating cells.[11]

In conclusion, this case highlights that even if lytic lesions are present at diagnosis in an epithelial malignancy, the patient should be worked up as a whole and all atypical findings like increased bleeding after a biopsy should be duly investigated.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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