Complete regression of primary cutaneous malignant melanoma associated with distant lymph node metastasis: a teaching case mimicking blue nevus

Abstract

Background: Malignant melanoma (MM) tends to be spontaneously regressed, however, complete regression of primary cutaneous MM is an extremely rare phenomenon. Our aim is to be aware that pathologists and/or dermatologists can readily misinterpret it as the other benign or malignant lesions.

Case presentation: A gradually growing and verrucous hypopigmented macule had been noticed in the right sole of a 65-year-old Japanese male since 2 years before, and it turned to be a solitary bluish to black patch with surrounding depigmentation and was recently decreased in size. In parallel, the patient had a rapidly growing black-pigmented mass lesion at the right inguen. The cutaneous specimen from the sole showed an aggregation of many melanophages predominantly in the middle to deep layer of dermis, associated with surrounding fibrosis, reactive vascular proliferation and CD8-positive T-lymphocytic infiltrate, covered by attenuated epidermis with absence of rete ridge. However, no remnant MM cells were completely seen in the step-serial sections. We first interpreted it as blue nevus. By contrast, the inguinal mass revealed a diffuse proliferation of highly atypical mono- to multi-nucleated large cells having abundant eosinophilic cytoplasm in the enlarged lymph node tissue. Immunohistochemical findings demonstrated that these atypical cells were specifically positive for HMB45 and Melan A. Therefore, we finally made a diagnosis of complete regression of primary cutaneous MM associated with distant lymph node metastasis of MM.

Conclusion: Careful, not only general/cutaneous but histopathological, examinations should be necessary and adjunctive aids for reaching the correct diagnosis of complete regression of cutaneous MM.

Fig. 1

Macroscopic and imaging findings of this complete regression of cutaneous MM on the right sole associated with right inguinal lymph node metastasis. a, b The patient had a solitary bluish to black patch with surrounding depigmentation, accompanied by recent decrease in size, measuring up to 20 mm in the right sole. In fact, he had noticed it as a gradually growing, hemorrhagic and verrucous hypopigmented macule since approximately 2 years before. Bar  2 cm. b In parallel, he suffered from a rapidly growing and painful black-pigmented mass lesion with surface skin ulcer at the right inguen especially for recent 2 months, partly extending to the right scrotum and thigh. Bar  5 cm. c A pelvic CT scan revealed a relatively well-defined huge and low-density mass with peripheral enhancement, measuring approximately 10 × 8 cm. Bar  5 cm

Fig. 2

Microscopic examination of the complete regression of primary cutaneous MM. a On low-power view of the surgical cutaneous specimen from the right sole, a hyperpigmented lesion was made up of an aggregation of melanophages with surrounding variably sclerotic fibrosis mainly in the middle to deep layer of dermis (H&E stains). The covering non-disordered epidermis exhibited attenuated and atrophic change with absence of rete ridge. Bar  2 mm. b On high-power view (H&E stains), these aggregated round to oval cells contained bland-looking small nuclei and abundant melanin-pigmented cytoplasm. In addition, immunohistochemically, these melanophages were strongly positive for CD68 (inset). Bar  50 μm. c In these fibrotic dermis, reactive vascular networks were noted, associated with mild interstitial and perivascular lymphocytic infiltrate. Furthermore the peripheral epidermis displayed exocytosis of focal nested lymphocytes (inset). Bar  500 μm. d In immunohistochemistry, dermal infiltrating CD8-positive T-lymphocytes (right) were markedly larger than CD4-positive T-lymphocytes (left) in number in this cutaneous lesion. Bar  1000 μm

Fig. 3

Gross and microscopic examination of the metastatic lymph node metastasis. a On gross findings of the surgical specimen from the inguinal to scrotal and femoral mass, the huge, relatively well-demarcated and multi-nodular tumor, measuring approximately 8 × 6 cm, showed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and yellowish necrotic foci. Bar  1 cm. b Microscopically, this inguinal tumor consisted of a diffuse proliferation of markedly atypical large cells, appearing predominantly as single cells (inset), involving and erasing the remarkably enlarged pre-existing lymph node tissue, partly surrounded by fibrous capsule (arrows). Bar  1000 μm. c On high-power view, these tumor cells contained hyperchromatic, pleomorphic mono- to multi-nuclei, and abundant eosinophilic to sometimes clear cytoplasm, admixed with a number of lymphocytes. Additionally, the large tumor cells occasionally had melanin pigments in the cytoplasm (left) and often showed autophagy (right). Bar  50 μm. d In immunohistochemistry, these malignant cells were specifically positive for melanocytic markers, such as HMB45 (left) and Melan A (right). Bar  100 μm