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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 24  |  Issue : 3  |  Page : 140-142

Pancytopenia as the Initial Presentation of Metastatic Prostate Cancer


1 Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Pathology, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission10-Jul-2020
Date of Decision10-Dec-2020
Date of Acceptance26-Dec-2020
Date of Web Publication21-Jan-2022

Correspondence Address:
Dr. Lt Col Vishal Mangal
Department of Internal Medicine, Armed Forces Medical College, Pune - 411 040, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jmms.jmms_150_20

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  Abstract 


Prostate cancer (PC) is the most prevalent malignancy in men (after lung cancer). It commonly presents with lower urinary tract symptoms such as urgency, hesitancy, and poor stream besides some patients may present with bone pain. Anemia is the most common presentation of solid tumors with bone marrow involvement, however, pancytopenia as the presenting feature is rare. Here, we describe a 60-year-old man with significant comorbidities in the past who now presented with symptomatic anemia without any urinary symptoms. On evaluation, he was found to have pancytopenia with elevated alkaline phosphatase levels. Work up for pancytopenia revealed metastatic deposits from the adenocarcinoma in the bone marrow. Further, he was diagnosed as a case of PC on transrectal prostate biopsy and managed with denosumab and maximal androgen blockade.

Keywords: Case report, pancytopenia, prostate cancer, recurrent stroke


How to cite this article:
Mangal V, Singhal P, Tilak T, Singh S, Hasvi J. Pancytopenia as the Initial Presentation of Metastatic Prostate Cancer. J Mar Med Soc 2022;24, Suppl S1:140-2

How to cite this URL:
Mangal V, Singhal P, Tilak T, Singh S, Hasvi J. Pancytopenia as the Initial Presentation of Metastatic Prostate Cancer. J Mar Med Soc [serial online] 2022 [cited 2022 Aug 18];24, Suppl S1:140-2. Available from: https://www.marinemedicalsociety.in/text.asp?2022/24/3/140/336184




  Introduction Top


Prostate cancer (PC) is the second-most prevalent malignancy (after lung cancer) in men worldwide. The incidence rate of PC varies across regions and populations. In 2018, PC represented 7.1% of all cancers in men.[1] African and Asian men have incidence rates that are lower than those from developed countries. PC incidence increases with age. Although only 1 in 350 men under the age of 50 years will be diagnosed with PC,[2] the incidence rate increases up to 1 in every 52 men for ages 50–59 years. The incidence rate is nearly 60% in men over the age of 65 years. PC commonly presents with lower urinary tract symptoms such as urgency, frequency, hesitancy, or bone pain due to metastasis to bone. Although bone is the most common site of metastasis from PC, bone marrow involvement occurs relatively less frequently.[3] Infiltration of bone marrow can result in bone marrow failure, manifesting as cytopenias involving multiple cell lines. Severe hematologic involvement of this kind is predictive of poor prognosis. Anemia is the most frequent presentation in patients with solid tumors with bone marrow involvement. Pancytopenia is seen only in 19% of cases.


  Case Report Top


A 60-year-old man with a significant past medical history of primary hypertension, diabetes mellitus and recurrent stroke (initially right middle cerebral artery ischemic stroke involving in 2013 followed by the second episode of ischemic stroke right hemi pons in September 2019 with partial recovery), presented with complaints of easy fatigability, anorexia, and generalized weakness of 3 months duration. He was initially evaluated at a private hospital and was found to have severe anemia with hemoglobin concentration of 49 g/L (reference range 140–180 g/L). He received two units of packed red blood cells before presentation to our center. There was no history of jaundice, pain abdomen, nausea, vomiting, loose stools, hematemesis, melena, per rectal bleeding, or hemorrhoids. He denied any history of fever, night sweats, weight loss, decreased urine output, or blood in the urine. General physical examination was unremarkable except for the presence of pallor. On examination of the nervous system, he had right hemiparesis with grade III power in all the muscle groups of upper limb and lower limb. The rest of the systemic examination was unremarkable. On baseline evaluation, he was found to have pancytopenia with Hb-71 g/L, total leukocytes count (TLC)-3.1 × 109/L and platelet count of 100 × 109/L (reference range TLC-4.5-11 × 109/L and platelet-150–450 × 109/L). His liver function tests revealed normal bilirubin and enzymes with markedly elevated alkaline phosphatase (ALP) level of 1848 U/L (reference range– 30–120 units/L) with serum albumin of 21 g/L (reference range– 35-55 g/L) and total protein level of 62 g/L (reference range– 55–90 g/L). His renal function tests revealed a serum creatinine level of 1.2 mg/dL (reference range– 0.70–1.30 mg/dL) with proteinuria of 30 mg/dL. Because of his raised ALP level, he underwent a skeletal survey, which revealed an osteosclerotic lesion in the fifth lumbar vertebra. Ultrasonography of his abdomen showed no evidence of biliary obstruction. With this initial picture of pancytopenia and recurrent stroke, the clinical diagnosis of Paroxysmal nocturnal hemoglobinuria was made. However, his bone marrow aspiration and biopsy studies revealed metastatic deposits from adenocarcinoma (likely prostate). Immunohistochemical (IHC) staining of tumor cells showed granular positivity for Alpha-methylacyl-CoA racemase (AMACR). CK7, CK20, and TTF-1 were negative [Figure 1] and [Figure 2].
Figure 1: Bone marrow biopsy: (H and E, ×40) Thickened bony trabeculae with marrow spaces showing no hematopoietic elements. Marrow is replaced by desmoplastic stroma infiltrated by atypical cells with high nuclear-cytoplasmic ratio depicted by red arrow

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Figure 2: Bone marrow biopsy: ×20 anti-prostate-specific antigen stain. The red arrow marks the brown color representing prostate-specific antigen in atypical cells

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The patient was subsequently evaluated for PC. His total prostate-specific antigen (PSA) levels were markedly raised to 421.5 ng/ml (reference range: 0-4.5 ng/ml). He underwent a whole-body positron emission tomography scan, which revealed multiple areas of sclerotic lesions in the entire axial and appendicular skeleton with heterogeneously increased fluorodeoxyglucose (FDG) uptake in fifth lumbar vertebra and left acetabulum with no abnormal focal FDG avidity in the prostate or any other solid organ. The patient underwent transrectal ultrasound (TRUS)-guided prostate biopsy. A total of seven cores from the right lobe of the prostate and six cores from the left lobe were sent for histopathological examination, which revealed prostatic adenocarcinoma in 12 cores of 13 fragments with modified Gleason score of 4 + 3 [Figure 3].
Figure 3: Transrectal ultrasound-guided prostate biopsy, (H and E, ×40) The red arrow show atypical cells with high nuclear-cytoplasmic ratio and hyperchromatic nuclei

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These results were discussed in the urology-oncology meeting, and he was started on maximum androgen blockade and denosumab for bone lesions. The patient is currently under oncology follow-up.


  Discussion Top


The median age of diagnosis of PC is 67 years only 35% of males are diagnosed between the ages of 55 and 63 years.[4] From an epidemiological standpoint, this patient was diagnosed relatively young at the age of 60 years. The United States Preventive Services Task Force has advised against the use of PSA for screening purposes.[5] The incidence of low-risk PC decreased during the years 2007–2013 to 37% less than that of 2004, the incidence of metastatic PC has risen to 72% for the same period. The most considerable increase in metastatic PC was seen in men aged 55–69 years.

Patients at these ages thought to most benefit from PC screening and early definitive treatment.[6] Patients with no urological complaints and patients who are not under urology follow-up or who did not have PSA screening can present with advanced disease. The suppression of blood cell lines causing pancytopenia is usually a finding in the later course of the disease, compared to an osteoblastic/osteoclastic activity. The mechanism is not fully understood, though recent studies in mice have demonstrated that PC cells can be directed to hematopoietic stem cell niches in bone marrow affecting the terminal differentiation of hematopoietic stem cells, and thus causes pancytopenia.[7] This atypical presentation, like pancytopenia alone, would make diagnosing prostate adenocarcinoma difficult without the lower urinary tract symptoms. Once adenocarcinoma has been identified, immunohistochemical markers may be utilized to help determine the lineage of the tumor.

This patient presented with pancytopenia, so a bone marrow biopsy was obtained, which showed granular positivity for AMACR and negativity for CK7, CK20, and TTF-1 on IHC. It is essential to understand the pattern of these IHC markers and to correlate them with the clinical scenario to truly maximize their efficacy. Bone involvement by solid tumors can be diagnosed on CT, MRI, or bone scan. It is sporadic to detect non-hematologic malignancy while examining the bone marrow biopsy. The detection of bone marrow metastatic deposits is essential to determine the stage of the malignancy, chemotherapeutic response, prognosis, and follow-up.[8] Hypercalcemia, bone pain, raised the level of ALP and LDH, unexplained cytopenias, and lytic or sclerotic bony lesions on radiology suggest bone marrow metastasis. This case highlights that there should be a low threshold for doing bone marrow examination in elderly patients presenting with pancytopenia.

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.

Acknowledgment

We would like to thank the Department of Urology, Command Hospital, Pune, India, for their support and guidance. We also would like to thank the Department of Nuclear Medicine, Command Hospital, Pune, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 1
    
2.
Perdana NR, Mochtar CA, Umbas R, Hamid AR. The risk factors of prostate cancer and its prevention: A literature review. Acta Med Indones 2016;48:228-38.  Back to cited text no. 2
    
3.
Mehdi SR, Bhatt ML. Metastasis of solid tumors in bone marrow: A study from northern India. Indian J Hematol Blood Transfus 2011;27:93-5.  Back to cited text no. 3
    
4.
Ahmad A, Tan W. Atypical presentation of prostate cancer and the workup of an adenocarcinoma of unknown primary. World J Oncol 2012;3:187-90.  Back to cited text no. 4
    
5.
Moyer VA. Screening for prostate cancer: U.S. Preventive services task force recommendation statement. Ann Intern Med 2012;157:120-34.  Back to cited text no. 5
    
6.
Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States. Prostate Cancer Prostatic Dis 2016;19:395-7.  Back to cited text no. 6
    
7.
Edwards CN, Steinthorsson E, Nicholson D. An autopsy study of latent prostatic cancer. Cancer 1953;6:531-54.  Back to cited text no. 7
    
8.
Mishra P, Das S, Kar R, Jacob SE, Basu D. Non-hematopoietic malignancies metastasising to the bone marrow: A 5-year record based descriptive study from a tertiary care centre in South India. Indian J Cancer 2014;51:30-4.  Back to cited text no. 8
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