Acral lentiginous melanoma (ALM) is the rarest of the four subtypes of cutaneous melanoma.1 It accounts for only 2-8% of melanomas in caucasians.2 Only 52 cases of ALM have been recorded in the Philippine Dermatological Society Health Information System from 2011 to 2016.3 Histopathologic demonstration of cytologic atypia, presence of mitoses in the deep dermis, pagetoid spread of epidermal melanocytes and lack of maturation of nests with descent into the dermis are features diagnostic of melanoma.2 4 ALM is primarily managed through wide surgical excision. The most common sites for ALM are the soles, palms, and subungual areas.2 The rarity of ALM, the inconspicuousness of the locations of some lesions, and the difficulty in discerning ALM from benign lesions and traumatic changes usually delay the diagnosis and contribute to the poor prognosis of the disease.4 5 6 A 53-year-old male consulted us for an enlarging pigmented plaque on the sole of his left foot. The lesion started as a junctional nevus, which the patient had since birth. The nevus, originally measuring approximately 0.5 x 0.5 cm, started to increase in size one year prior to the consultation. One month before consultation, the patient noted a black nodule on the center of the lesion. A week before consultation, the lesion bled and became painful after manipulation by the patient. Dermatologic examination of the plantar aspect of the left foot revealed a 1.7 x 1.6 cm, dark brown-black, asymmetric plaque with cobblestone-like surface and a black indurated nodule on the center (Figure 1A). Dermoscopic findings of bluish white veil and irregular pigmentation with variable hypopigmented blotches are suggestive of acral melanoma (Figure 1B). Skin punch biopsy and immunohistochemical stains for S100, Melan A, HMB-45, and KI-67 confirmed the diagnosis of ALM (Figure 2, 3). We did a wide local excision of the lesion with a 2-cm margin from the tumor edge, with depth up to the suprafascial level (Figure 4A). The excisional defect was repaired with a split-thickness skin graft taken from the patient’s skin on the right thigh (Figure 6), which provided excellent aesthetic result. We also did a sentinel lymph node biopsy on the left inguinal area (Figure 5A,B). Frozen section biopsy showed solid nests of atypical melanocytes invading the surrounding fibrous stroma. Individual cells exhibit round to oval, deeply basophilic nuclei and abundant, clear to eosinophilic cytoplasm. Some areas showed prominent melanin pigmentation. Sections along lines of resection, lymphovascular channels, nerves and adipose tissues of the excised mass (Figure 4 B,C) and lymph nodes from sentinel biopsy were all devoid of malignant tumor cells. Histopathologic findings from frozen section biopsy and permanent section biopsy were both consistent with malignant melanoma with 3 mm Breslow thickness. The patient’s postoperative course, including wound healing, was uneventful (Figure 7). During the patient’s 12-month follow up period, we did not observe any signs of local or distant recurrence of the tumor.
Melanoma, Cutaneous Malignant ; Skin Transplantation

Acral lentiginous melanoma (ALM) is the rarest of the four subtypes of cutaneous melanoma.1 It accounts for only 2-8% of melanomas in caucasians.2 Only 52 cases of ALM have been recorded in the Philippine Dermatological Society Health Information System from 2011 to 2016.3 Histopathologic demonstration of cytologic atypia, presence of mitoses in the deep dermis, pagetoid spread of epidermal melanocytes and lack of maturation of nests with descent into the dermis are features diagnostic of melanoma.2 4 ALM is primarily managed through wide surgical excision. The most common sites for ALM are the soles, palms, and subungual areas.2 The rarity of ALM, the inconspicuousness of the locations of some lesions, and the difficulty in discerning ALM from benign lesions and traumatic changes usually delay the diagnosis and contribute to the poor prognosis of the disease.4 5 6 A 53-year-old male consulted us for an enlarging pigmented plaque on the sole of his left foot. The lesion started as a junctional nevus, which the patient had since birth. The nevus, originally measuring approximately 0.5 x 0.5 cm, started to increase in size one year prior to the consultation. One month before consultation, the patient noted a black nodule on the center of the lesion. A week before consultation, the lesion bled and became painful after manipulation by the patient. Dermatologic examination of the plantar aspect of the left foot revealed a 1.7 x 1.6 cm, dark brown-black, asymmetric plaque with cobblestone-like surface and a black indurated nodule on the center (Figure 1A). Dermoscopic findings of bluish white veil and irregular pigmentation with variable hypopigmented blotches are suggestive of acral melanoma (Figure 1B). Skin punch biopsy and immunohistochemical stains for S100, Melan A, HMB-45, and KI-67 confirmed the diagnosis of ALM (Figure 2, 3). We did a wide local excision of the lesion with a 2-cm margin from the tumor edge, with depth up to the suprafascial level (Figure 4A). The excisional defect was repaired with a split-thickness skin graft taken from the patient’s skin on the right thigh (Figure 6), which provided excellent aesthetic result. We also did a sentinel lymph node biopsy on the left inguinal area (Figure 5A,B). Frozen section biopsy showed solid nests of atypical melanocytes invading the surrounding fibrous stroma. Individual cells exhibit round to oval, deeply basophilic nuclei and abundant, clear to eosinophilic cytoplasm. Some areas showed prominent melanin pigmentation. Sections along lines of resection, lymphovascular channels, nerves and adipose tissues of the excised mass (Figure 4 B,C) and lymph nodes from sentinel biopsy were all devoid of malignant tumor cells. Histopathologic findings from frozen section biopsy and permanent section biopsy were both consistent with malignant melanoma with 3 mm Breslow thickness. The patient’s postoperative course, including wound healing, was uneventful (Figure 7). During the patient’s 12-month follow up period, we did not observe any signs of local or distant recurrence of the tumor.
Melanoma, Cutaneous Malignant ; Skin Transplantation

Humans ; Melanoma/therapy* ; Skin Neoplasms/therapy* ; Methylation ; Prognosis ; Immunotherapy ; RNA ; Biomarkers, Tumor ; Melanoma, Cutaneous Malignant

Humans ; Sarcoma, Clear Cell/pathology* ; Melanoma/pathology* ; Skin Neoplasms/pathology* ; Diagnostic Errors ; Soft Tissue Neoplasms ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference (P=0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference (P=0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration (HR=0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis (HR=0.486, 95% CI: 0.285-0.828), stage ⅢC (HR=0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations (HR=0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P=0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P=0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Apoptosis ; China ; Disease-Free Survival ; East Asian People ; Immunotherapy ; Interferon-alpha/therapeutic use* ; Lymphatic Metastasis ; Melanoma/pathology* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Skin Neoplasms/pathology* ; Melanoma, Cutaneous Malignant