Paraneoplastic leukemoid reaction in a patient with BRAF V600E-mutated metastatic malignant melanoma

Abstract

A paraneoplastic leukemoid reaction is a rare condition of extreme leucocytosis in patients with solid malignancies. The differential diagnosis is often a true challenge. We present a case of a 56-year old woman with a history of stage IIIA malignant melanoma resected in 2004 that was diagnosed in May 2013 with BRAF V600E-mutated metastatic disease (left arm mass, lungs and adrenal glands). The laboratory findings revealed leucocytosis with granulocytosis that increased progressively to values up to 120.0 × 10(9)/L. After a diagnostic work-up, a diagnosis of a paraneoplastic leukemoid reaction was established. We report the response of leucocytosis to radiation and BRAF inhibitor therapy, albeit short-lived. To the best of our knowledge, this is the first case report of a paraneoplastic leukemoid reaction in metastatic melanoma with characterisation of BRAF V600 mutation status. It remains unclear whether the aggressive tumour phenotype is related to the leukemoid reaction and whether this is related to the BRAF mutation.

BRAF V600Q-mutated lung adenocarcinoma with duodenal metastasis and extreme leukocytosis

“…It is also possible that her poor outcome was related to a paraneoplastic leukemoid reaction. Interestingly, neutrophilic leukemoid reaction was reported in a patient with BRAF V600E-mutated metastatic melanoma[ 27 ]. In another report, a case of squamous cell carcinoma with peritoneal carcinomatosis and an eosinophilic leukemoid reaction showed coexistence of the BRAF V600E and oncogenic KRAS G12A mutations[ 28 ].…”

Paraneoplastic leukemoid reactions induced by cytokine-secreting tumours

“…LR can be caused by infections, intoxications, malignancies, severe haemorrhage or acute haemolysis 3. Paraneoplastic leukemoid reaction (PLR) can be defined as the LR which occurs due to the presence of a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour 4…”

“…The first PLR due to CST was reported in 1977 in a patient with lung cancer 5. Since then, it has been reported in patients with melanoma, mesothelioma, carcinomas and sarcomas of various origins (biliary tree, oesophagus, gallbladder, head and neck, liver, stomach, urinary bladder and thyroid) 1 4 6–17…”

“…Clinical presentation of CSTs can be widely variable, and therefore challenging. Patients usually present with fever and/or symptoms related to the underlying malignancy 4 14. If the underlying malignancy is not clinically apparent, tumour-induced leukocytosis could easily be mistaken for infection or myeloproliferative neoplasm (MPN) 23.…”

“…If the underlying malignancy is not clinically apparent, tumour-induced leukocytosis could easily be mistaken for infection or myeloproliferative neoplasm (MPN) 23. This, in turn, can lead to unnecessary diagnostic procedures, such as bone marrow aspiration and biopsy with extensive molecular and ancillary testing 4 15 21. The presence of fever can distract the treating clinician’s attention to pursue a diagnosis of infection instead of PLR as the cause of unexplained leukocytosis.…”