Surgery remains as a mainstream treatment in current melanoma therapy. Most surgeries for melanoma aim to eradicate all melanoma cells in the body, leading to the “cure” of patients. However, recent investigations reveal that melanoma cells disseminate early and form single-cell metastases or micrometastases, which remain dormant for long periods of time (parallel progression model). Furthermore, metastasis may be a multidirectional process whereby cancer cells can seed distant sites as well as the primary tumor itself (tumor self-seeding). Reframing our understanding of melanoma biology urges a review of current therapeutic routines for melanoma. While excision of a primary tumor could prevent melanoma progression by interfering tumor self-seeding even in patients with stage IV disease, the role of complete lymph node dissection following a positive sentinel node biopsy should be reconsidered.
Lymphangioleiomyomatosis (LAM) is a rare disease that is characterized by proliferation of abnormal smooth muscle-like cells (LAM cells). It almost exclusively affects females and typically develops before menopause. LAM cells generally affect the lung and then disseminate to the axial lymphatic system, including the lymph nodes and thoracic duct. They produce potent lymphangiogenic growth factors (VEGF-C and VEGF-D) and induce the proliferation of lymphatic vessels. A 44-year-old woman visited our department complaining of swelling of the left thigh. She had no respiratory symptoms. The patient showed slight redness and localized edema on the medial side of her left thigh. Hematoxylin and eosin stains from the skin biopsy revealed the enlargement of lymphatic vessels without endothelial cell atypia. A computer tomography scan showed numerous cysts in her bilateral lungs and axial lymphatics. Based on these findings, the patient was diagnosed with LAM. Although respiratory symptoms are common and often initially found in patients with LAM, skin alterations are rare as an initial sign of this disease. This atypical case, who initially developed swelling in the left thigh, makes it clear that LAM should be considered as a differential diagnosis in patients with edema of unknown origin.
A 34-year-old woman presented with fever, central diabetes insipidus, xanthelasma palpebrarum, subcutaneous masses in the trunk, and long bone involvement. Based on skin and bone biopsies, she was diagnosed as Erdheim-Chester disease (ECD), one of the non-Langerhans cell histiocytoses. Despite administration of oral steroids and immunosuppressants as well as other treatments, little improvement was observed, and the subcutaneous masses gradually increased in size and number. Immunohistochemistry revealed that the infiltrating foamy histiocytes were diffusely positive for TNF-α. Therefore, we treated her with infliximab, an anti-TNF-α monoclonal antibody. After two administrations of infliximab, the subcutaneous masses decreased in size. Although the treatment strategy for ECD is still controversial, anti-TNF-α monoclonal antibody could be one of the therapeutic options.
A 79-year-old Japanese male presented with bilateral post-auricular blisters, which had appeared several days before the first examination. On histopathological examination, HE staining revealed subepidermal blisters, and direct immunofluorescence detected deposits of IgG and C3 in the basement membrane zone. Indirect immunofluorescence revealed linear IgG anti-basement membrane zone antibodies, which reacted with the dermal side of 1M salt-split skin. Immunoblotting revealed that IgG reacted with α3, β3 and γ2 subunits of purified human laminin 332. These findings led us to a diagnosis of anti-laminin 332 mucous membrane pemphigoid. The patient was treated with prednisolone 60 mg/day and diaminodiphenyl sulfone 75 mg/day, which did not alleviate the disease. Therefore, 400 mg/kg/day high dose immunoglobulin therapy was then prescribed for 5 days, resulting in rapid improvement of the lesions. When the immunological analyses were repeated after alleviation of the lesions, indirect immunofluorescence detected no IgG anti-basement membrane zone antibodies. Immunoblotting using purified laminin 332 revealed that IgG was still positive for γ2, but not for α3 and β3 subunits, suggesting that the α3 and β3 subunits were the pathogenic antigens in this patient.