|Year : 2020 | Volume
| Issue : 1 | Page : 186-188
A case of paraneoplastic hyperleukocytosis closely mimicking chronic neutrophilic leukemia
Navkirti Mittal1, Ruchi Gupta1, Khaliqur Rahman1, Parshw Singh1, Ipsita Panda2, Soniya Nityanand1
1 Department of Hematology, SGPGI, Lucknow, Uttar Pradesh, India
2 Department of Pathology, SGPGI, Lucknow, Uttar Pradesh, India
|Date of Submission||11-Aug-2016|
|Date of Decision||20-Sep-2016|
|Date of Acceptance||01-Oct-2016|
|Date of Web Publication||03-Feb-2017|
Department of Hematology, SGPGI, Lucknow - 226 014, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Leukemoid reaction and myeloproliferative syndrome are close mimickers and frequently pose a diagnostic dilemma, particularly when the leukocyte count is very high. Leukocyte alkaline phosphatase score frequently aids in diagnosis but may or may not be contributory, especially in differentiating chronic neutrophilic leukemia. Herein, we document a case of leukemoid reaction with extensive hyperleukocytosis in a 46-year-old female with poorly differentiated carcinoma. The tumor itself as well as the associated leukocytosis portends a poor prognosis.
Keywords: Diagnostic dilemma, hyperleukocytosis, leukocyte alkaline phosphatase score, leukemoid reaction, myeloproliferative syndrome
|How to cite this article:|
Mittal N, Gupta R, Rahman K, Singh P, Panda I, Nityanand S. A case of paraneoplastic hyperleukocytosis closely mimicking chronic neutrophilic leukemia. J Can Res Ther 2020;16:186-8
|How to cite this URL:|
Mittal N, Gupta R, Rahman K, Singh P, Panda I, Nityanand S. A case of paraneoplastic hyperleukocytosis closely mimicking chronic neutrophilic leukemia. J Can Res Ther [serial online] 2020 [cited 2020 May 30];16:186-8. Available from: http://www.cancerjournal.net/text.asp?2020/16/1/186/199434
| > Introduction|| |
Hyperleukocytosis is defined as a leukocyte count >100,000 cells/μL. It is usually associated with myeloproliferative neoplasms (MPNs) or a consequence to varied etiologies such as infections, malignancies, intoxications, severe hemorrhage, and acute hemolysis. Reported here is a case of paraneoplastic hyperleukocytosis associated with a total leukocyte count (TLC) of more than 200 × 109/L and absolute neutrophil count of 197 × 109 cells/μL, thereby closely mimicking chronic neutrophilic leukemia (CNL). To the best of our knowledge, this is the first case report of paraneoplastic hyperleukocytosis with such high counts.
| > Case Report|| |
A 46-year-old female presented with pain in the left lumbar region radiating to groin with loss of appetite, dyspepsia, and intermittent fever of 15 days duration. There was no history of associated constitutional symptoms such as night sweats or weight loss. There was no history of recent drug intake, particularly growth factors and corticosteroids. On examination, she had tenderness in the left iliac fossa on deep palpation; however, there was no palpable organomegaly. Computed tomography (CT) of the abdomen showed a large well-defined, hypodense, heterogeneous space occupying lesion of size 7.5 cm × 7.2 cm × 10.4 cm in the retroperitoneum occupying the left lumbar fossa and iliac fossa region. The mass was present along the belly of left psoas muscle. Magnetic resonance imaging scan revealed well-defined heterogeneously enhancing mass in the retroperitoneum at the level of organ of Zuckerkandl. The left adrenal and kidney were identified separately from the mass. CT-guided paravertebral mass biopsy revealed a malignant tumor, the cells of which showed moderate to severe nuclear pleomorphism, hyperchromatic nuclei, occasional prominent nucleoli, and scant to moderate amount of eosinophilic cytoplasm. On immunohistochemistry (IHC), the tumor cells were positive for cytokeratin (CK) (strong and diffuse), vimentin (moderate and focal), and CK7 and thyroid transcription factor 1 (faintly positive). The cells were negative for CD10 and CK20, overall suggesting a poorly differentiated malignant epithelial tumor with sarcomatoid differentiation [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Further, synaptophysin, S100 (IHC stains) were negative and 24 h urine metanephrine and normetanephrine levels were near-normal, ruling out the possibility of paraganglioma. Her complete blood count analysis revealed a TLC of 215 × 109/L, hemoglobin of 8.7 g/dl, platelet count of 274 × 109/L. Other comprehensive blood tests, including kidney function, liver function test, and electrolytes, were normal. Peripheral blood smears showed striking neutrophilia [Figure 2] with the absence of shift cells such as myelocytes, metamyelocytes, or band cells. A few activated neutrophils showing toxic granules and cytoplasmic vacuoles were noted. Besides, there was no basophilia, eosinophilia, monocytosis, or any dysplasia feature. Leukocyte alkaline phosphatase (LAP) score was high normal [Figure 2] inset]. Blood and urine cultures were sterile. Qualitative as well as quantitative polymerase chain reaction for JAK2V617F and all three BCR-ABL transcripts, namely p190, p210, and p230, were negative [Figure 3]. Immunophenotypic characteristics of neutrophils gated in bright CD45 region with high-side scatter showed CD13 positive, CD15 positive while being negative for CD34 and Human Leucocyte Antigen-D related (HLA-DR). The patient had a rapid downhill course and was subsequently lost to follow-up.
|Figure 1: Histological section (a) showing malignant tumor cells with moderate to severe nuclear pleomorphism, hyperchromatic nuclei, occasional prominent nucleoli, and moderate amount of eosinophilic cytoplasm. Immunohistochemistry (b-d) showing tumor cell positivity for cytokeratin (b) (strong and diffuse), vimentin (c) (moderate and focal), and negative for leukocyte common antigen (d); (a: H and E, oil immersion, b: IHC, oil immersion, c and d: ×40)|
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|Figure 2: Peripheral blood smears showing neutrophilia with the absence of shift cells such as myelocytes and metamyelocytes. Other cell lines such as eosinophils, basophils, and monocytes are not seen (Leishman, ×40). Inset – Stain with leukocyte alkaline phosphatase was high normal in the neutrophils (oil immersion)|
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|Figure 3: Polymerase chain reaction for JAK2V617F (a) and BCR-ABL (b) showing negative results|
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| > Discussion|| |
Paraneoplastic hyperleukocytosis is a rare condition that can be challenging to diagnose and requires a comprehensive workup. Hyperleukocytosis has been described in patients with varied solid malignancies such as lung, skin, urothelial cancer and sarcomas.,, A retrospective study by Granger et al . over a period of 3 years revealed approximately 20% (758/3770) cases of solid tumors associated with leukocytosis, of which 10% (77) patients had a paraneoplastic etiology, whereas others were found to be associated with infections and drugs, particularly growth factors. Lung cancer was found to be the most common culprit malignancy. The mechanism of neutrophilia is attributed to an accelerated release of neutrophils from the bone marrow, which might be the result of underlying tumoral secretion of cytokines, granulocyte colony-stimulating factor (G-CSF), and interleukin-6., G-CSF is a pleiotropic cytokine known for its specific effects on the proliferation and activation of hematopoietic cells of the neutrophilic granulocyte lineage. G-CSF-producing tumors are typically poorly differentiated, rapidly progressing and with a large tumor burden and have been found to have a dismal prognosis. Stathopoulos et al . analyzed the prognostic significance of G-CSF in nonsmall cell lung cancers and observed a shorter survival in patients with high leukocyte count and is elevated G-CSF levels. Dorn et al . described a case of 57-year-old woman with very high leukocyte count, having a poorly differentiated neoplasm which was associated with rapidly progressive course suggesting that hyperleukocytosis in solid tumors, invariably portents an inferior outcome.
In cancer patients with a high leukocyte count, a series of meticulous investigations should be carried out to rule out other secondary causes such as infections, drug intake, or coexistent leukemia. The previously reported leukocyte counts in such scenario usually ranged from 40,600/μL to 115,100/μL, with a mean of 53,000/μL; however, the current case had an extremely high leukocyte count of 215,000/μL, thereby raising the clinical suspicion of a concomitant MPN. However, the absence of splenomegaly, left shift, blasts, eosinophilia, basophilia, thrombocytosis, and BCR-ABL fusion transcript aided in excluding MPN. Nonetheless, differentiating between paraneoplastic hyperleukocytosis and CNL would be challenging because both conditions share identical morphological features, including predominant neutrophilia, a raised LAP score, and the absence of the BCR/ABL translocation. Although few authors have proposed the role of HLA-DR in differentiating reactive neutrophilia from CNL, its validity of immunophenotyping as a differential tool is not established. The neutrophils, in reactive hyperleukocytosis, are negative for HLA-DR, as was seen in our case. A few studies have shown usefulness of human androgen receptor gene assay and presence of cytogenetic abnormalities in some cases. Recently described mutations included in the diagnostic criteria of CNL are CSF 3R T618I or other activating CSF3R mutations. However, owing to the limited availability of these diagnostic tests, the CNL mainly remains a diagnosis of exclusion. Since the present case had a retroperitoneal neoplastic mass, absence of hepatosplenomegaly, and rapid deteriorating condition of the patient, a diagnosis of paraneoplastic hyperleukocytosis was entertained.
| > Conclusion|| |
Paraneoplastic leukocytosis is an uncommon manifestation of solid tumors. A thorough workup is required to differentiate it from MPN. Moreover, it requires a timely surgical intervention since it is known to have a poor prognostic impact as was seen in our patient as well.
We would like acknowledge Mr. Akhilesh, Technical Staff, Flow Cytometry Laboratory.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]