Case Study: Did This Melanoma Metastasize or Is It Something Else?

"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

What is the cause of the indurated subcutaneous nodules that appeared suddenly in a woman in her 40s who had recent surgery for malignant melanoma? That was the diagnostic dilemma faced by Alejandra Sandoval-Clavijo, MD, MSc, of the University of Barcelona in Spain, and colleagues, in evaluating a patient whose medical history also included multiple sclerosis, for which she was receiving subcutaneous interferon β-1a.

Case Description

As the authors reported in their case study in JAMA Dermatology, the patient noted that 3 weeks earlier a desmoplastic melanoma (Breslow thickness of 1 mm) had been excised with 1-cm margins and she had undergone a left axillary sentinel lymph node biopsy (SLNB) under general anesthesia.

Physical examination identified two indurated and mobile subcutaneous nodules on the anterior surface of the arm measuring 15 mm and 4 mm in diameter. These were located 5 cm from the previous surgical site. When she extended her arm to 90°, she said, she felt mild tightness but no pain. Examination also revealed a subtle cord that projected from the largest nodule to the axillary region.

Clinicians excised and biopsied the larger lesion, which revealed dilated and thrombosed vessels in the subcutaneous tissue, with signs of recanalization. The medical team also observed edema, areas of acute hemorrhage, and signs of recent fibrosis and focal steatonecrosis. There was no evidence of malignant melanoma.

Lab tests confirmed that the lesion had originated from the lymphatic vasculature, with expression for CD31, ERG, and D2-40 (podoplanin) antibodies; herpesvirus 8 was not detected.

The team also performed SOX10 staining, which ruled out metastatic melanoma. Based on the results of the staining and the patient's recent SLNB of the left axilla, clinicians made a diagnosis of axillary web syndrome (AWS).

Discussion

This case was a rare presentation of AWS, which is a known complication of SLNB in the setting of breast cancer, typically developing within 12 weeks of the biopsy, but is highly unusual after SLNB for cutaneous malignant melanoma, the authors noted.

Clinical features, as described in a 2016 study that called AWS an underappreciated complication of sentinel node biopsy in melanoma, include "palpable tight cords in the axilla that can extend to the arm, antecubital space, and forearm, associated with pain and movement restriction of the affected segment."

In rare cases such as this patient's, it may result in "painless, mobile subcutaneous nodules in the ipsilateral arm of the SLNB," Sandoval-Clavijo and co-authors said.

They suggested that cord formation may occur when the surgical procedure interferes with the superficial lymphatics and vessels of the arm, leading to thrombosis. Histopathologically, AWS is marked by "dilated and thrombosed superficial veins, lymphatics, or both," authors noted, adding that positive findings of the D2-40 stain support the condition's lymphatic origin.

Differential Diagnoses

Several diagnoses must be considered when melanoma patients who have undergone surgery suddenly develop nodules, Sandoval-Clavijo and co-authors noted. In addition to the eventual diagnosis of AWS in this patient, possible etiologies include intravascular papillary endothelial hyperplasia or Masson tumor, pseudo-aneurysmal metastasis of melanoma, and traumatic humeral pseudo-aneurysm.

Masson tumor is a rare vascular tumor involving intravascular proliferation of endothelial cells. The condition is slightly more common in women and is notable for "intravascular proliferation of endothelial cells with papillary formations, almost always associated with some thrombus, with each papillary frond covered by plump endothelial cells," the case authors wrote. Typically the tumors are negative for D2-40, while the cells lining the papillae of the tumor are positive for CD31, CD34, alpha smooth muscle actin, and factor VIII–related antigen.

Cutaneous melanoma is an aggressive cancer that spreads easily. The metastases tend to show proliferation of atypical melanocytes and, in challenging cases, immunohistochemical markers such as SOX-10, HMB-45, MelanA, and microphthalmia-associated transcription factor will reveal amelanotic differentiation, the team explained.

Brachial pseudo-aneurysms are uncommon and often caused by injury or postsurgical iatrogenic damage. They present as swelling, painful pulsatile masses under the traumatic/scar area, the case authors wrote: "The walls of the pseudo-aneurysm contain variable amounts of laminated clot, surrounded by dense fibrous tissue reaction, marked accumulation of endothelial and muscle cells and deposition of proteoglycans." Like melanoma metastases, brachial pseudo-aneurysms are negative for D2-40.

Sandoval-Clavijo and co-authors concluded by urging clinicians to consider the possibility of AWS in patients with cutaneous melanoma who develop sudden subcutaneous nodules near surgical scars shortly after an SLNB. The presence of a palpable cord, often subtle, adjacent to the nodule, may help rule out melanoma metastasis and confirm axillary web syndrome as the cause of the nodules, the group stated.

Read previous installments in this Medical Journeys series:

Part 1: Melanoma: Epidemiology, Diagnosis, and Treatment

Part 2: Recognizing Melanoma: What It Is, What It Isn't

Part 3: Basics of Melanoma Diagnosis

Part 4: Case Study: The Dangers of Melanoma Recurrence

Part 5: Managing Early-Stage Melanoma

Part 6: Managing Unresectable/Metastatic Melanoma: What to Know