Polypoid Pedunculated Amelanotic Melanoma

A 74-year-old woman presented with a large, ulcerated, and fungating mass on her left cheek (Figure 1). She stated that the lesion had begun 1 year ago as a slow-growing, pinto bean-sized, pink macule on her left cheek, and had since grown into a large nodule that bled occasionally. She denied any prior surgery or trauma to the affected area. Her family history was negative for melanoma or other skin cancers. Her past medical history was significant for hypertension.

Physical examination. At the initial consultation, an exophytic, pedunculated, ulcerated mass measuring 3.5 cm in diameter was present on her left cheek. Induration and erythema were present at the base of the growth. The lesion was suspected most likely to be a squamous cell carcinoma.

Diagnostic tests. A shave biopsy was performed, removing the lesion at its base, and was sent for pathology examination. The biopsy revealed an ulcerated malignant melanoma (MM) invading to a depth of at least 15 mm (Clark level IV, Breslow depth stage III). The neoplasm extended diffusely to the base of the specimen, with extensive ulceration of the surface. No definite regression was present, and numerous dermal mitotic figures were identified (10 mitoses/mm²) (Figures 2 and 3). Immunohistochemistry results for S100 protein (a common marker for melanoma) were strongly positive.

Treatment. She was immediately referred to a surgical oncologist for the management of melanoma, and she subsequently underwent a modified excision around the prior scar site. A modified nasal flap was constructed; the final closure measured 1.7 × 2.4 cm. The margins from the excision site, examined via frozen section, were clear. No nodal involvement was seen in 2 sentinel nodes, which had been removed via careful dissection along the facial and marginal mandibular lymphatics.

The final tumor-node-metastases (TNM) classification of the patient’s melanoma stage was T4bN0M0, or stage III. Results of serum indices and chest radiograph findings were unremarkable. The patient declined the recommended adjuvant interferon treatment.

Article continues on page 2

Outcome of the case. After surgery, the patient was instructed to follow up for wound care. At a follow-up visit several months later, examination of the surgical site revealed a well-healed scar (Figure 4). She has had a 3-year disease-free period and has regular follow-up visits at our dermatology clinic.

Discussion. Melanoma is generally classified into 4 subtypes: nodular, acral lentiginous, lentigo maligna, and superficial spreading. This classification was devised after observation of variable and characteristic patterns on histology that could be correlated with distinctive clinical presentations.

The polypoid pedunculated melanoma (PPM) subtype was first described in 1958 by Vogler and colleagues,¹ but the literature continues to be scant regarding polypoid, pedunculated, or exophytic melanomas. Most authors who have researched polypoid, pedunculated, or exophytic skin melanomas consider this entity a variant of nodular melanoma.² Reports of a polypoid morphology in melanomas range from approximately 2% to 43%.³ One large retrospective study showed that the prevalence of a pedunculated morphology of melanoma to be 5.8%,⁴ while another study showed the prevalence to be higher, at 21.5%.⁵ The reported occurrence rate of polypoid melanoma is extremely variable in the literature, likely due to different clinical and pathologic criteria used to characterize it.

This neoplasm may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions. PPM may mimic clinical features of cutaneous squamous cell carcinoma, keratoacanthoma, nodular basal cell carcinoma, and Merkel cell carcinoma. These conditions were included among our patient’s differential diagnoses due to her history of a nonhealing growth in a sun-exposed area. Cutaneous lymphoma, large pyogenic granuloma, and ulcerative melanoma were also considered.

The amelanotic PPM variant occurs much less frequently than its pigmented counterpart, and as such, diagnosis and treatment are often delayed.⁶ Histologic examination of our patient’s biopsy specimen showed a strongly positive S100 immunostain, a stain that is immunoreactive in 96% to 99% of cases of melanoma.⁷ This finding supported the final diagnosis of MM in our patient.

Although several cases have been reported, PPM (and particularly the amelanotic variant) certainly is not common. Amelanotic melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. The prevalence of the amelanotic subtype has been estimated between 1.8% and 8.1% of all melanomas,⁸ and this subtype is difficult to diagnose due to the lack of the melanin pigment typically found in melanomas.

MM tumors grow rapidly and are prone to metastasis at an early stage of disease. Hematogenously spread, MM can metastasize to regional lymph nodes as well as the gastrointestinal tract, lungs, brain, paratesticular tissue, and bone marrow. Furthermore, PPMs have a poor prognosis, which is related to the unusually large thickness and ulceration and not to the pedunculated shape of the lesion.⁹

In an analysis of 17,600 cutaneous melanomas for TNM staging, Balch and colleagues demonstrated that tumor thickness and ulceration were the most powerful predictors of survival in the T (tumor) category.¹⁰ Our patient had a T4bN0M0 or resectable stage III melanoma. T4b describes melanomas of greater than 4.0 mm in thickness with ulceration. According to Balch and colleagues’ study, a stage III melanoma has a 5-year survival rate of 13% to 69%.

Wide local excision of the primary tumor with 2-cm margins remains the first-line therapy in such cases.¹¹ No survival advantage is demonstrated with wider resection margins. Because stage III melanoma represents nodal disease, performing a regional lymph node dissection is also recommended. Additional standard treatment options for a resectable stage III melanoma include adjuvant chemotherapy such as high-dose interferon alfa-2b and pegylated interferon.¹² However, prospective, randomized, multicenter trials have demonstrated that such treatments improve relapse-free survival but do not improve overall survival.

Immunotherapy with checkpoint inhibitors such as pembrolizumab, nivolumab, and ipilimumab, which are undergoing further investigative clinical trials, have been approved by the Food and Drug Administration for the treatment of resectable stage III disease as well as unresectable stage III, stage IV, and recurrent melanoma.

This article was orignally published in Consultant. 2017;57(7):429-434.

Dr Clark is with Skin Cancer and Cosmetic Dermatology Centers, Dalton, GA.
Ms Jorge is with Skin Cancer and Cosmetic Dermatology Centers, Dalton, GA.

Disclosure: The authors report not relevant financial relationships.

References:

1. Vogler WR, Perdue GD, Wilkins SA Jr. A clinical evaluation of malignant melanoma. Surg Gynecol Obstet. 1958;106(5):586-594.

2. Knezević F, Duancić V, Sitić S, et al. Histological types of polypoid cutaneous melanoma II. Coll Antropol. 2007;31(4):1049-1053.

3. Cutler K, Chu P, Levin M, Wallack M, Don PC, Weinberg JM. Pedunculated malignant melanoma. Dermatol Surg. 2000;26(2):127-129.

4. Manci EA, Balch CM, Murad TM, Soong SJ. Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol. 1981;75(6):810-815.

5. McGovern VJ, Shaw HM, Milton GW. Prognostic significance of a polypoid configuration in malignant melanoma. Histopathology. 1983;7(5):663-672.

6. Morton CA, Mackie RM. Clinical accuracy of the diagnosis of cutaneous malignant melanoma. Br J Dermatol. 1998;138(2):283-287.

7. Aisner DL, Maker A, Rosenberg SA, Berman DM. Loss of S100 antigenicity in metastatic melanoma. Hum Pathol. 2005;36(9):1016-1019.

8. Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol.2000;42(5 pt 1):731-734.

9. Agostini P, Rivero A, Parra Martin JA, Soares-de-Almeida L. Pedunculated polypoid melanoma: a case report of a rare spindle-cell variant of melanoma. Dermatol Online J.2015;21(4):10.

10. Balch CM, Soong S-J, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622-3634.

11. Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4mm) primary melanoma. Ann Surg Oncol. 1998;5(4):322-328.

12. PDQ Adult Treatment Editorial Board. Melanoma Treatment (PDQ^®): Health Professional Version. Bethesda, MD: National Cancer Institute. https://www.ncbi.nlm.nih.gov/books/NBK66034. Published January 26, 2017. Accessed June 20, 2017.

A 74-year-old woman presented with a large, ulcerated, and fungating mass on her left cheek (Figure 1). She stated that the lesion had begun 1 year ago as a slow-growing, pinto bean-sized, pink macule on her left cheek, and had since grown into a large nodule that bled occasionally. She denied any prior surgery or trauma to the affected area. Her family history was negative for melanoma or other skin cancers. Her past medical history was significant for hypertension.

Physical examination. At the initial consultation, an exophytic, pedunculated, ulcerated mass measuring 3.5 cm in diameter was present on her left cheek. Induration and erythema were present at the base of the growth. The lesion was suspected most likely to be a squamous cell carcinoma.

Diagnostic tests. A shave biopsy was performed, removing the lesion at its base, and was sent for pathology examination. The biopsy revealed an ulcerated malignant melanoma (MM) invading to a depth of at least 15 mm (Clark level IV, Breslow depth stage III). The neoplasm extended diffusely to the base of the specimen, with extensive ulceration of the surface. No definite regression was present, and numerous dermal mitotic figures were identified (10 mitoses/mm²) (Figures 2 and 3). Immunohistochemistry results for S100 protein (a common marker for melanoma) were strongly positive.

Treatment. She was immediately referred to a surgical oncologist for the management of melanoma, and she subsequently underwent a modified excision around the prior scar site. A modified nasal flap was constructed; the final closure measured 1.7 × 2.4 cm. The margins from the excision site, examined via frozen section, were clear. No nodal involvement was seen in 2 sentinel nodes, which had been removed via careful dissection along the facial and marginal mandibular lymphatics.

The final tumor-node-metastases (TNM) classification of the patient’s melanoma stage was T4bN0M0, or stage III. Results of serum indices and chest radiograph findings were unremarkable. The patient declined the recommended adjuvant interferon treatment.

Article continues on page 2

Outcome of the case. After surgery, the patient was instructed to follow up for wound care. At a follow-up visit several months later, examination of the surgical site revealed a well-healed scar (Figure 4). She has had a 3-year disease-free period and has regular follow-up visits at our dermatology clinic.

Discussion. Melanoma is generally classified into 4 subtypes: nodular, acral lentiginous, lentigo maligna, and superficial spreading. This classification was devised after observation of variable and characteristic patterns on histology that could be correlated with distinctive clinical presentations.

The polypoid pedunculated melanoma (PPM) subtype was first described in 1958 by Vogler and colleagues,¹ but the literature continues to be scant regarding polypoid, pedunculated, or exophytic melanomas. Most authors who have researched polypoid, pedunculated, or exophytic skin melanomas consider this entity a variant of nodular melanoma.² Reports of a polypoid morphology in melanomas range from approximately 2% to 43%.³ One large retrospective study showed that the prevalence of a pedunculated morphology of melanoma to be 5.8%,⁴ while another study showed the prevalence to be higher, at 21.5%.⁵ The reported occurrence rate of polypoid melanoma is extremely variable in the literature, likely due to different clinical and pathologic criteria used to characterize it.

This neoplasm may mimic benign and malignant variants of both melanocytic and nonmelanocytic lesions. PPM may mimic clinical features of cutaneous squamous cell carcinoma, keratoacanthoma, nodular basal cell carcinoma, and Merkel cell carcinoma. These conditions were included among our patient’s differential diagnoses due to her history of a nonhealing growth in a sun-exposed area. Cutaneous lymphoma, large pyogenic granuloma, and ulcerative melanoma were also considered.

The amelanotic PPM variant occurs much less frequently than its pigmented counterpart, and as such, diagnosis and treatment are often delayed.⁶ Histologic examination of our patient’s biopsy specimen showed a strongly positive S100 immunostain, a stain that is immunoreactive in 96% to 99% of cases of melanoma.⁷ This finding supported the final diagnosis of MM in our patient.

Although several cases have been reported, PPM (and particularly the amelanotic variant) certainly is not common. Amelanotic melanoma is a subtype of cutaneous melanoma with little or no pigment on visual inspection. The prevalence of the amelanotic subtype has been estimated between 1.8% and 8.1% of all melanomas,⁸ and this subtype is difficult to diagnose due to the lack of the melanin pigment typically found in melanomas.

MM tumors grow rapidly and are prone to metastasis at an early stage of disease. Hematogenously spread, MM can metastasize to regional lymph nodes as well as the gastrointestinal tract, lungs, brain, paratesticular tissue, and bone marrow. Furthermore, PPMs have a poor prognosis, which is related to the unusually large thickness and ulceration and not to the pedunculated shape of the lesion.⁹

In an analysis of 17,600 cutaneous melanomas for TNM staging, Balch and colleagues demonstrated that tumor thickness and ulceration were the most powerful predictors of survival in the T (tumor) category.¹⁰ Our patient had a T4bN0M0 or resectable stage III melanoma. T4b describes melanomas of greater than 4.0 mm in thickness with ulceration. According to Balch and colleagues’ study, a stage III melanoma has a 5-year survival rate of 13% to 69%.

Wide local excision of the primary tumor with 2-cm margins remains the first-line therapy in such cases.¹¹ No survival advantage is demonstrated with wider resection margins. Because stage III melanoma represents nodal disease, performing a regional lymph node dissection is also recommended. Additional standard treatment options for a resectable stage III melanoma include adjuvant chemotherapy such as high-dose interferon alfa-2b and pegylated interferon.¹² However, prospective, randomized, multicenter trials have demonstrated that such treatments improve relapse-free survival but do not improve overall survival.

Immunotherapy with checkpoint inhibitors such as pembrolizumab, nivolumab, and ipilimumab, which are undergoing further investigative clinical trials, have been approved by the Food and Drug Administration for the treatment of resectable stage III disease as well as unresectable stage III, stage IV, and recurrent melanoma.

This article was orignally published in Consultant. 2017;57(7):429-434.

Dr Clark is with Skin Cancer and Cosmetic Dermatology Centers, Dalton, GA.
Ms Jorge is with Skin Cancer and Cosmetic Dermatology Centers, Dalton, GA.

Disclosure: The authors report not relevant financial relationships.

References:

1. Vogler WR, Perdue GD, Wilkins SA Jr. A clinical evaluation of malignant melanoma. Surg Gynecol Obstet. 1958;106(5):586-594.

2. Knezević F, Duancić V, Sitić S, et al. Histological types of polypoid cutaneous melanoma II. Coll Antropol. 2007;31(4):1049-1053.

3. Cutler K, Chu P, Levin M, Wallack M, Don PC, Weinberg JM. Pedunculated malignant melanoma. Dermatol Surg. 2000;26(2):127-129.

4. Manci EA, Balch CM, Murad TM, Soong SJ. Polypoid melanoma, a virulent variant of the nodular growth pattern. Am J Clin Pathol. 1981;75(6):810-815.

5. McGovern VJ, Shaw HM, Milton GW. Prognostic significance of a polypoid configuration in malignant melanoma. Histopathology. 1983;7(5):663-672.

6. Morton CA, Mackie RM. Clinical accuracy of the diagnosis of cutaneous malignant melanoma. Br J Dermatol. 1998;138(2):283-287.

7. Aisner DL, Maker A, Rosenberg SA, Berman DM. Loss of S100 antigenicity in metastatic melanoma. Hum Pathol. 2005;36(9):1016-1019.

8. Koch SE, Lange JR. Amelanotic melanoma: the great masquerader. J Am Acad Dermatol.2000;42(5 pt 1):731-734.

9. Agostini P, Rivero A, Parra Martin JA, Soares-de-Almeida L. Pedunculated polypoid melanoma: a case report of a rare spindle-cell variant of melanoma. Dermatol Online J.2015;21(4):10.

10. Balch CM, Soong S-J, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol. 2001;19(16):3622-3634.

11. Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick (>4mm) primary melanoma. Ann Surg Oncol. 1998;5(4):322-328.

12. PDQ Adult Treatment Editorial Board. Melanoma Treatment (PDQ^®): Health Professional Version. Bethesda, MD: National Cancer Institute. https://www.ncbi.nlm.nih.gov/books/NBK66034. Published January 26, 2017. Accessed June 20, 2017.