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A 49-year-old man presents to an emergency department in Jacksonville, Florida, for a rash on the right side of his chest along with skin lesions. On physical examination, he seems confused, although not distressed or agitated. He is unable to provide any details about his medical history, except to say that he received treatment recently for shingles.

Clinicians note scars in the area of his right scapula. Examination reveals a dark red papular skin rash on the right side of his chest, located at the fourth and fifth intercostal areas (dermatomal T2 and T3 distribution) and extending to the back of his armpit area, where multiple hard lumps are palpated in groups. The lesions are tender to the touch, with purulent discharge.

In light of the patient's recent history of what clinicians suspect was herpes zoster and his immunocompromised status, the team initiates empirical treatment with acyclovir 1 g intravenously every 8 hours. However, the firmness of the skin lesions and significant swelling of his axillary lymph nodes raise concerns about a possible underlying malignancy, and the clinicians proceed with a skin biopsy to rule out cancer.

Later in the patient's admission, the team receives his medical records and the family provides additional details about the patient's history.

Clinicians discover the following: Two years previously, the patient was diagnosed with cutaneous melanoma in the right scapular area. This was treated surgically with complete resection, and chemotherapy was started. After undergoing one cycle of chemotherapy, the patient declined to continue treatment.

More recently, he was admitted after developing a second skin lesion in the same area, which was also resected. Biopsy reveals cells strongly positive for S-100, the protein usually found in neural crest cells like melanocytes, and a melanoma-specific marker, Melan-A immunostain.

Biopsy results are negative for cytokeratin AE1/AE3 immunostain -- typically an epithelial/myoepithelial cell marker. The medical team considers the findings supportive of a diagnosis of metastatic amelanotic melanoma. Computed tomography (CT) of the chest identifies signs of subcutaneous invasion, lung metastasis, and metastatic bony lesions.

In consideration of the patient's poor functional status and the minimal benefit further treatment is likely to offer, clinicians counsel the patient and family regarding palliative care, and the decision is made for discharge with hospice care. No further treatment is administered.

Discussion

Clinicians presenting this rare of a zosteriform rash found to be a recurrence of metastatic amelanotic melanoma note the importance of considering the whole clinical picture, even when presented with what appears to be typical zoster lesions. In this case, a bedside skin punch biopsy helped hasten the correct diagnosis.

Zosteriform metastasis is a cutaneous manifestation of malignancy, similar in presentation to the dermatomal rash that occurs in reactivation of the varicella zoster virus. The pattern is characterized by grouped vesicles on an erythematous base restricted to one unilateral dermatome, and tends to be painful, tender, or pruritic. Diagnosis is complicated by the fact that the condition is usually confined to a single unilateral dermatome.

There have been only a few documented cases of recurrence of melanoma in a "zosteriform transformation" following chemotherapy treatment, as was the case in this patient. The authors' literature review revealed only seven other similar presentations.

There are several possible mechanisms of melanoma metastasis, including direct injury to the skin, with neuronal and dorsal root ganglia involvement. Cancers with the greatest tendency to metastasize to the skin are melanoma (45% of cutaneous metastasis cases) and cancers of the breast (30%), nasal sinuses (20%), larynx (16%), and oral cavity (12%). In contrast, while prostate cancer is very common, cutaneous metastasis is relatively uncommon.

The case authors note that while skin rashes are frequently encountered in daily practice, amelanotic melanoma is a rare type of melanoma that, due to a lack of melanin in the lesion, lacks the darkened appearance typical of a melanoma. This atypical presentation means that amelanotic melanoma is often unrecognized, leading to delayed diagnosis, a longer period of metastasis, and poorer prognosis.

This patient's history and overall presentation helped focus the clinical investigations.

Diagnosis

Due to the rarity of zosteriform metastasis of melanoma, clinicians should consider a wide range of differential and common diagnoses, including herpes simplex virus, atopic dermatitis, superficial pyoderma, eczema, furunculosis, secondary/tertiary syphilis, post-herpetic granulomatous dermatitis, and sarcoidosis, the case authors note.

They add that biopsy followed by histopathologic confirmation and immunostaining that identifies melanoma-specific markers, S-100 and Melan-A markers, can confirm diagnosis.

The exact cause of this form of metastasis is not clear; there are several theories suggesting that past varicella infections may provide an opportunity for later metastasis, either through or neuronal injury or lymphatic invasion through involvement of dorsal root ganglia, or post-surgically, via direct cutaneous seeding after resection of the previous lesion, thus accounting for involvement of areas close to the previous melanoma.

This form of melanoma is typically treated in the same way as "traditional" melanoma, and depends on the staging, the case authors explain, adding that lesions should receive supportive care with radiation therapy. Clinicians should aim for prevention of secondary infection with de-roofing or hydrocolloid dressings, and immune modulator imiquimod 5% cream may help regression of metastases in some patients.

Follow-up surveillance for melanoma recurrences, especially after treatment for an advanced stage tumor, is a key factor in improving prognosis, the case authors note, adding that some advise CT or positron emission tomography (PET) imaging to assess regional lymph nodes.

Conversely, a assessing ultrasound, CT, PET, and PET/CT for staging and surveillance in over 10,000 patients with melanoma found that for the primary staging of regional lymph nodes, ultrasound was the most sensitive technique (60% median score, 95% CI 33%-83%), followed by PET (30% median score, 95% CI 12%-55%), PET/CT (11% median score, 95% CI 1%-50%), and CT (9% median score, 95% CI 12%-55%).

Similarly, the meta-analysis showed that for lymph node surveillance in melanoma patients, ultrasound was the most sensitive technique (96% median score, 95% CI 85%-99%). PET/CT was the most sensitive modality for both staging and surveillance of distant metastases (80% median score, 95% CI 53%-93% for staging; 86% median score, 95% CI 76%-93% for surveillance).

In the current case, the authors note that they did not have surveillance and imaging information when the patient presented for care; this lack of medical background and the presence of new skin lesions prompted the team to do a skin biopsy. And while there is no data to suggest zosteriform presentation of melanoma specifically has an impact on prognosis, cutaneous manifestations of metastasis are generally associated with a poorer prognosis.

Conclusions

The case authors conclude that even in the face of typical zoster lesions, it is important that physicians conduct a thorough assessment of the clinical picture in its entirety since early diagnosis of recurrent melanoma with biopsy (aided by imaging when indicated by the initial tumor stage) can improve outcome and prognosis.

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