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Melanoma Manifesting as Tumoral Melanosis; Now You See It, Now You Don't

Grohs, Robert L. MBBS*; Mesbah Ardakani, Nima MD, FRCPA*,†

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The American Journal of Dermatopathology: June 2018 - Volume 40 - Issue 6 - p 462-465
doi: 10.1097/DAD.0000000000000848
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To the Editor:

Tumoral melanosis (also known as nodular melanosis) is a rare but distinctive histologic process characterized by large aggregates of densely pigmented melanophages in the skin, often seen in a regressed pigmented melanocytic lesion.1 Although partial regression is a relatively common finding in melanoma, tumoral melanosis with complete absence of melanocytes is exceedingly rare.1 Herein, we describe a case of completely regressed cutaneous melanoma, in which the diagnosis of tumoral melanosis on a partial biopsy led to further investigation with detection of concurrent nodal metastatic disease.

A 60-year-old woman presented with 1-year history of a dark-brown pigmented lesion on her right calf, measuring 15 × 5 mm. She had no history of previous skin cancer and no familial or personal history of melanoma. The lesion was clinically suspected to be a melanoma. A diagnostic incisional biopsy was performed to confirm the clinical suspicion.

Histological examination of the incisional biopsy showed nodular aggregates of melanophages, largely involving the dermis and extending to the superficial subcutis to a depth of 4.8 mm. There was surrounding areas of coarse extracellular melanin pigment deposition and foci of necrosis with no definite melanocytes seen (Figs. 1 and 2A). Immunohistochemistry (IHC) for melanocytic markers including Melan-A, SOX10, and HMB45 showed no melanocytes (Fig. 2B). Interestingly, there was also absence of junctional melanocytes in the overlying epidermis. The possibility of a completely regressed melanoma was raised; therefore, the patient underwent further clinical and imaging assessment.

Incisional biopsy from the lesion on the leg revealed an area of tumoral melanosis characterized by aggregate of melanin-laden macrophages and dermal necrosis [hematoxylin and eosin (H&E)].
A, High power view of the cutaneous lesion shows sheets of melanophages with no discernible melanocytes (H&E). B, Immunostaining for SOX10, using red chromogen, confirms the absence of melanocytes (SOX10 IHC with red chromogen). Note the red nuclear staining in the eccrine gland myoepithelial cells serving as an internal positive control (black circle), and brown melanin pigment in the background.

On further clinical examination, the woman was found to have right inguinal lymphadenopathy. Whole-body positron emission tomography (PET)/computed tomography scan demonstrated fludeoxyglucose uptake in an enlarged right femoral lymph node, with multiple small mildly avid right inguinal and distal external iliac lymph nodes. The original right calf cutaneous lesion showed possible postsurgical inflammatory change or residual malignancy on PET scan. No other fludeoxyglucose-avid metastatic disease was seen. An ultrasound-guided fine needle aspiration and core biopsy of the inguinal lymph node was performed. The core biopsy showed small aggregates of malignant spindle to epithelioid cells with pleomorphic nuclei, prominent nucleoli, and moderate amphophilic cytoplasm (Fig. 3). Mitotic figures were readily identified. In addition, there were large areas of tumor melanosis with aggregates of melanophages and areas of necrosis. On immunohistochemistry, the malignant cells showed strong positivity for melanocytic markers including Melan-A (Fig. 4), SOX10, HMB45, and S100, consistent with metastatic malignant melanoma. Similar malignant melanocytes were seen on cytology smears from the fine needle aspiration.

A, A core biopsy from the inguinal lymph node confirmed metastatic melanoma, characterized by sheets of malignant melanocytes and extensive nodal melanosis toward the left side of the section (H&E). B, High power view demonstrates malignant melanocytes with enlarged pleomorphic and hyperchromatic nuclei, and multiple mitotic figures (black arrows, H&E), which express Melan-A melanocytic marker by immunohistochemistry (inset, Melan-A IHC with red chromogen).
Metastatic melanoma in the lymph node (high power illustration in the inset), with associated extensive nodal melanosis at the left side of this image (H&E).

Further right inguinal/groin dissection identified 6 lymph nodes, one of which contained a large deposit of metastatic malignant melanoma (22 mm in largest dimension). This was characterized by sheets of malignant melanocytes with frequent mitosis and large areas of necrosis with masses of melanophages (Fig. 5). There was no extranodal extension. Right iliac, common iliac, and right groin dissection identified several lymph nodes with large sheets of melanophages and no residual melanocytes.

A formal excision of the cutaneous lesion demonstrated the extent of tumoral melanosis in the dermis with focal involvement of the subcutaneous tissue.

The original lesion on the right calf was completely excised. Histologic examination showed extensive dermal and focally subcutaneous tumoral melanosis, characterized by nodular sheets of melanophages in the dermis and subcutis to a maximum depth of 4 mm. There were no melanocytes in the dermis or subcutaneous tissue (Fig. 6). Given the clinical context, a diagnosis of extensive tumoral melanosis compatible with a completely regressed invasive malignant melanoma was rendered.

High power view of tumoral melanosis shows a fibrotic stroma with extensive melanin deposition and numerous melanophages (H&E), expressing CD163 histiocytic marker by immunohistochemistry (inset, CD163 IHC with red chromogen).

Tumoral melanosis or nodular melanosis is a rare but recognized phenomenon, characterized by excessive extracellular melanin and melanin-laden macrophages arranged in sheets in the dermis or subcutaneous tissue.2 There are still many unanswered questions surrounding etiology, incidence, and prognostic significance, likely due to the very few reported cases.3 These histological appearances, specifically in the presence of a rapidly growing pigmented cutaneous lesion with or without regional or distant lymphadenopathy, are often suggestive of an aggressive malignant melanoma. This rapidly developing tumor can invoke an extensive immunological response resulting in partial or complete regression of the lesion. Similar phenomenon can be seen in a lymph node.4 In this context, nodal melanosis is a preferable term indicating that there are no identifiable melanoma cells in the node.5 This case signifies the need to have a high index of suspicion of a melanocytic malignancy with metastatic potential when dealing with tumoral melanosis in the skin. Extensive regression in melanoma appears to be limited to the adults and older patients, and typical of superficial spreading melanoma.6

The prognostic significance of regression in melanoma is a subject of debate in the literature, and the reported data are conflicting. The cumulative data suggest that partial regression in less than 50%–75% of tumor cells does not affect prognosis;7 however, complete or extensive regression in more than 50%–75% of lesional tissue is associated with an aggressive clinical course and often with concurrent metastatic disease, as seen in our case,8–10 to the extent that in many patients the nodal disease comes to the clinical attention before the primary tumor. In the patients who do not present with nodal disease, a sentinel lymph node biopsy should be considered, even if the primary lesion is thin and does not fulfill the current criteria for this procedure. In addition, a thorough workup, involving a complete review of systems including skin, ophthalmological, and mucosal (oral, nasal, anorectal, and vulvar/vaginal) examination and PET scan, is prudent.1,5,11

Dermal necrosis identified in the cutaneous lesion in our case is not typical of the late stage (cicatricial stage) of tumoral melanosis and certainly not part of the diagnostic criteria for this entity. However in early inflammatory stage, it is expected that a severe immune reaction or neoplastic crisis in melanoma cells incites an influx of inflammatory cells (mostly lymphocytes) with consequent tumor necrosis, cell lysis, and pigment incontinence.6 The areas of necrosis will be eventually replaced by aggregates of macrophages, and later by fibrosis/scarring. Therefore, the presence of necrosis indicates an early stage of tumoral melanosis rather than an advanced lesion; however, the clinical and prognostic significance of this finding is not clear.

The potential clinical and histological differential diagnoses of tumoral melanosis include deep penetrating nevus, pigmented epithelioid melanocytoma/epithelioid blue nevus, and animal-type melanoma. Although all these entities often show significant melanin pigmentation and numerous melanophages, they consistently contain a component of viable melanocytes of variable morphology. In deep penetrating nevus and melanocytoma, the melanocytes show a rather bland appearance with round to oval nuclei, inconspicuous nucleoli, and sparse mitotic figures. In contrast, animal-type melanoma exhibits more prominent cytologic atypia. Rare cutaneous melanotic schwannoma, which can occur both sporadically and in patients with Carney complex, may also enter the differential diagnosis. However, this latter tumor is usually located in the paraspinal region, and is composed of epithelioid to spindle cells with hybrid features of Schwann cells and melanocytes and variable degree of cytologic atypia.12 Psammomatous calcifications (if present) are usually a good clue to the diagnosis.

In addition, early stage of tumor melanosis in a melanoma may mimic the regressive and inflammatory change seen in a benign nevus with halo phenomenon; however, this alteration is often partial in a nevus and benign histological features can be appreciated in the residual melanocytes present. Finally, it should be noted that tumoral melanosis is not restricted to the melanocytic lesions. It has also been associated with pigmented epithelial lesions in the skin including pigmented basal cell carcinoma, pigmented seborrheic keratosis, and solar lentigines as well as pigmented epithelial lined cysts,1 which add to the complexity of the diagnosis.

In conclusion, we describe a rare case of tumoral melanosis in a completely regressed cutaneous malignant melanoma with concurrent metastatic disease. This case raises the awareness of this phenomenon and signifies the necessity of thorough clinical and imaging workup to search for potential metastatic disease on identification of tumoral/nodular melanosis in the skin, as by the time the diagnosis is made the outcome is often poor.


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