Isolated metastatic melanoma to the pancreas in the context of myeloproliferative neoplasm: a rare occurrence

Abstract

Isolated metastatic melanoma to the pancreas is a rare occurrence, representing less than 1 per cent of metastatic melanoma. This case describes the clinical presentation and course of illness of a patient who was diagnosed with a solitary metastasis to the pancreas 11 months after a clear margin resection of a pT1b, stage IB melanoma. Her melanoma metastasis was diagnosed on Endoscopic Ultrasound-Fine Needle Biopsy (EUS-FNB). This patient was found to have a concurrent myeloproliferative neoplasm (MPN) at the time of diagnosis. This case importantly highlights the course of a rare finding in isolated metastatic melanoma to the pancreas that may have been accelerated by the patient’s immunocompromised state with concurrent MPN. A high index of suspicion must be raised in patients with abdominal symptoms and melanoma history as the therapeutic window for these patients is quite narrow.

Background

Malignant melanoma can rarely metastasise to the gastrointestinal tract. Although rare, pancreatic metastases should be considered in patients with a history of melanoma. The presence of MyeloproliferativeNeoplasm (MPN) may accelerate the clinical course of a malignancy, in this case melanoma. This may warrant a more intensive surveillance regimen following the diagnosis of melanoma.

Case presentation

A 69-year-old non-smoking woman with a history of hypertension, who was otherwise healthypresented to her family physician with a pigmented lesion on her left arm which had changed in colour and size over 9 months; a deep shave biopsy revealed a 1 mm Breslow depth melanoma. She was then referred to a plastic surgeon and had a wide local excision with 1–1.5 cm margins. A nuclear imaging study was performed for sentinel node localisation, and two left axillary lymph nodes were marked and resected by plastic surgery. The pathology from both the local excision and axillary lymph node biopsy were negative. Her melanoma was staged at pT1b, stage IB. Positron Emission Tomography (PET) imaging showed no distant metastases.

She had been doing well in follow-up until 11 months after her initial treatment, when she presented to her family physician with abdominal pain radiating to her back with associated nausea. Blood work demonstrated a new leucocytosis (22×10⁹/L) with 82% neutrophils and a new normocytic anaemia (haemoglobin 105 g/L). C reactive protein levels were elevated (99.11 mg/L). Carbohydrate Antigen (CA) 19–9 levels were normal. An enhanced CT scan of her abdomen and pelvis revealed a large, heterogenous, low density, 6.3 × 4.5 cm mass arising from the pancreas suspicious for primary pancreatic malignancy or lymphoma. There was no evidence of metastatic disease related to this pancreatic lesion. The radiographic appearance of the mass was felt to be unusual for an adenocarcinoma of this size to present without ductal dilation. Pancreatic lymphoma was a consideration on the differential at this juncture, as it commonly presents on CT imaging as a homogenous solid mass without ductal dilation.

The patient was referred to both haematology and hepatopancreatobiliary (HPB) surgery. HPB reviewed her urgently and referred her to gastroenterology for endoscopic ultrasound (EUS) for biopsy for tissue diagnosis of this pancreatic mass (figure 1).

Figure 1.

On endoscopic ultrasound (EUS) in the pancreatic body, a 7 cm mass was visualised with some anechoic internal foci, suggestive of possible areas of necrosis. The mass was in close proximity to the splenic artery and vein.

After her EUS was completed, a CT biphasic pancreatic protocol was performed the next day to expedite her care (figure 2).

Figure 2.

CT biphasic pancreatic protocol. There is a large heterogenous hypoattenuating mass arising from the body of the pancreas. The mass measures 7.4 × 6.8 x 5.6 cm and demonstrates a thickened irregular wall and central low density. No internal calcifications are identified. There is mild pancreatic atrophy and dilation of the main pancreatic duct upstream from the mass. There is splenic artery and vein involvement. The left portal and main portal veins are splayed around and partially effaced by the mass. There is no definite involvement of the Superior Mesenteric Vein (SMV).

The pathology from her EUS biopsy revealed metastatic melanoma (figure 3). Molecular profiling revealed a pathogenic NRAS mutation (c.181C>A;p.Q61K). There was no evidence of BRAF (including V600E/K) or KIT mutations. She was not a surgical candidate due to the extensive tumour involvement of surrounding structures noted on biphasic CT scan.

Figure 3.

Pathology slides from EUS FNA sample. (A) H&E stain, 10 x magnification showing highly fragmented necrotic and inflammatory tissue. (B) H&E stain, 200 x magnification showing malignant epithelioid cells with marked pleomorphism on a background of necrosis and inflammation. (C) Micropthalmia transcription factor (MITF) immunostain, 200 x. There is focal nuclear MITF expression in tumour cells. (D) SOX10 (SRY-related HMG-box 10) immunostain, 200 x. There is nuclear SOX10 expression in the majority of tumour cells.

The patient was also reviewed by haematology 1 month later and had a bone marrow biopsy and aspirate which were negative for lymphoma. However, she did have TET2 positive MPN that was identified on cytogenetic and molecular analysis from serum blood. The patient was referred to medical oncology; however, she had unfortunately deteriorated very quickly and was too frail to receive any palliative chemotherapy. She was referred to palliative care and died several days later. The patient died before the MPN work up and haematology consult was fully completed. However, the most likely diagnosis was chronic myelogenous leukaemia (CML). She did not have the BCR-ABL transcript that 95% of patients with CML have, but there was evidence of TET2 mutation, marked persistent WBC elevation, and bone marrow biopsy showing panmyelosis. She did not have polycythaemia, and her platelet counts were not persistently elevated enough to qualify for a diagnosis of essential thrombocytosis (ET) or myelofirbrosis (MF).

Investigations

• Endoscopic ultrasound and biopsy of pancreas lesion.

• Bone marrow biopsy and apirate.

Differential diagnosis

Relevant differential diagnoses included a primary pancreas adenocarcinoma or lymphoma or metastases from another primary source.

Treatment

Palliative care.

Outcome and follow-up

• Patient died several weeks after diagnoses were made.

Discussion

Pancreatic metastases are quite rare, comprising 2%–5% of pancreatic malignancies.¹ The most common primary malignancies which metastasise to the pancreas include renal, lung, breast and colon. Melanoma is much less common.

The prognosis of patients with malignant melanoma metastatic to the pancreas is not clear, owing to a small number of cases in the literature. A 28 patient case series of isolated metastatic melanoma to pancreas demonstrated a survival benefit when treated with surgery versus without with median survivals of 23.8 and 15.2 months, respectively.²

The risk of concurrent malignancies, including melanoma, is increased with MPN. This risk exists even if patients have not received chemotherapy for an MPN.³ Our patient’s relatively immunocompromised state due to the underlying MPN may have also increased her susceptibility to metastasis and to its rapid growth. Her life span after diagnosis, as noted above, was far less than what the prior literature would dictate.²

To our knowledge, there are no case reports of melanoma with pancreatic metastases in the context of concurrently diagnosed MPN. In this case, the patient deteriorated quickly and was unable to benefit from surgery or newer immune checkpoint inhibitor therapies for metastatic melanoma.

Learning points.

• Metastases to pancreas are very rare, but should be considered in the case of patients with a history of malignant melanoma.

• A concurrent diagnosis of myeloproliferative neoplasm (MPN) in patients with melanoma may lead to more rapid tumour growth and metastases.

• Melanoma patients with concurrent diagnosis of MPN may benefit from more rigorous surveillance imaging.

• If detected early, metastatic melanoma lesions to the pancreas can be treated either medically or surgically, which can prolong patient survival.

Ethics statements

Patient consent for publication

Consent obtained from next of kin.