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Diagnosing And Treating Primary Malignant Melanoma In The Hallux

Noting the danger of misdiagnosis, these authors discuss the diagnosis and treatment of primary malignant melanoma in the hallux in a 94-year-old patient.

Malignant melanoma in the foot is a rare malignancy and proper diagnosis is often delayed. Although rare, when malignant melanoma arises in the foot, it is more likely a secondary form due to metastasis. Misdiagnosis can often lead to a delay in proper treatment and poorer outcome.

Malignant melanoma is a type of cancer of the skin secondary to the proliferation of melanocytes.1 In women, these lesions are most common on the legs and for men, they are most common on the back. The primary cause of melanoma is ultraviolet light. Treatment typically includes excision but can also include immunotherapy, biologic therapy, radiation or chemotherapy. With treatment, the five-year survival rate is 98 percent for those with localized disease and 17 percent among those with metastasis. Although melanoma accounts for less than 5 percent of skin cancers, it accounts for more than 75 percent of skin cancer deaths.

Reportedly up to 15 percent of all cutaneous melanomas are localized to the foot and ankle with melanoma being the most common neoplasm.2 When malignant melanoma is the primary lesion on the foot or ankle, mortality rates drop to 52 percent at five years in comparison to 84 percent when appearing elsewhere on the lower extremity.3  

One of the most important prognostic indicators for melanoma is time from onset to diagnosis. With early detection, melanoma is treatable and often curable. With this in mind, clinicians have utilized the ABC mnemonic for fast and reliable diagnosis of melanoma.4 Due to the morbidity associated with misdiagnosis, all physicians should keep this mnemonic in mind as well as newer ones such as CUBED when evaluating a suspicious skin lesion.5

Based on these criteria, if melanoma is a plausible diagnosis, order a biopsy promptly.4

A Closer Look At The Patient Presentation

A 94-year-old African-American male presented to our wound care center for the care of a wound he had on his left hallux. The patient was a very poor historian. He was unsure of how long he had the wound but maintained that he had it for quite some time. Previous providers had been administering local wound care consisting of dressing changes and infrequent debridements.

Upon presentation, the lesion was grossly hypertrophic with a reddened, cauliflower-like appearance. The lesion involved the entirety of the nail bed, extending to the distal aspect of the dorsal hallux.

Plain film radiographs did not show any bony involvement or periosteal reaction. Laboratory test results were normal.  

To confirm a diagnosis, we obtained a 3 mm skin punch biopsy. Microscopically, the biopsy showed a spindle cell neoplasm having non-distinctive morphology consisting of cells with palely eosinophilic cytoplasm and atypical hyperchromatic nuclei. The pathologist went on to classify this as “sarcoma not otherwise specified” and recommended complete excision for further evaluation and definitive diagnosis upon removal.

Six weeks after biopsy results, the patient had a hallux amputation at the level of the first metatarsophalangeal joint (MPJ). The delay was due to awaiting pathology’s assessment as well as surgical planning with the patient. Upon amputation, the proximal phalangeal base appeared healthy with no cortical changes. Subsequent clinical follow-up proved unremarkable.

The pathologist described the specimen as a melanoma of the nail bed of the left great toe, measuring approximately 4.5 cm x 3.0 cm x 2.5 cm. The lesion was mostly spindle cell proliferations with medium-sized to small oval cells involving the dermal/epidermal junction with associated melanin pigment. The overall histopathology and immunophenotype of the tumor was consistent with the diagnosis of a malignant melanoma with a predominant spindle cell component. The surgical margin of the amputation was focally positive for melanoma representing microsatellitosis with a mitotic rate of more than 15 mitotic figures per square millimeter. The additional proximal margin was negative for melanoma. Additionally, bone scan results showed no other sites of osseous involvement or metastasis.

Key Insights On Detecting Malignant Melanoma

For this patient, plain film imaging was not suggestive of any bony involvement. An adequate biopsy was essential for proper diagnosis and was delayed for several months in this case. Although the punch biopsy did not elucidate the definitive diagnosis, it did still guide treatment as malignancy was present with recommendations for excision. Surgical removal of the hallux allowed further examination as to the pathology. The images above show the difference between the obtained punch biopsy and the final surgical specimen. Note the comparison between the SOX-10 staining.

SOX-10 is a key nuclear transcription factor for differentiating neural crest progenitor cells from melanocytes. Researchers have demonstrated that SOX-10 is sensitive and specific as a marker for malignant melanoma, noting up to 100 percent identification of malignancy.6

When malignant melanoma presents as a primary lesion in the lower extremity, patients have an excellent prognosis with five-year survival rates at 98 percent post-treatment.6 Most often, however, when one discovers malignant melanoma in the lower extremity, it is often a secondary lesion and sign of metastasis. This offers a much grimmer prognosis with a 17 percent five-year survival rate.1 Additionally, subungual lesions occurred on the hallux 92 percent of the time and were associated with a survival rate of 17 percent at 10 years.7,8 Correspondingly, lesions localized to the plantar surface and subungual sites are associated with a higher prevalence of clinical misdiagnosis.9   

Acral lentiginous melanoma in Asians, Africans and the Middle Eastern population shows a significantly higher prevalence in comparison to Caucasians, and accounts for up to 70 percent of all melanomas.10 Other studies cite an accompanying poorer prognosis secondary to a delay in diagnosis. The mean delay in diagnosis ranges from 9 to 18 months with more advanced staging upon diagnosis and a lower estimated five-year survival rate.10

For this patient, proper diagnosis did not occur until surgical intervention with subsequent pathological examination of surgical specimen. Punch biopsy, however, was useful in elucidating the invasive nature of the lesion and identifying a spindle cell neoplasm.

In Conclusion

In the aforementioned case, a 94-year-old African-American male presented with a primary malignant melanoma in the hallux nail bed that went undiagnosed for several months. The patient had a thorough workup and a successful hallux amputation. The surgical margins showed malignant melanoma and the clean margins we obtained were negative for further infiltration. A bone scan was negative for metastasis. Early accurate diagnosis through punch biopsy will lead to more favorable outcomes with decreased likelihood of metastasis and poorer outcomes.

Dr. Ogden is an attending physician within the Norton Hospital system in Louisville, Ky.

Dr. Cicero is a first year resident in the Norton Hospital system in Louisville, Ky.

Dr. Troxell is a second year resident in the Norton Hospital system in Louisville, Ky.

The authors especially thank Lisa-Wills Frank, MD for her collaboration.

References

  1. American Cancer Society. Cancer facts and figures 2011. Available at https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2011.html . Accessed April 2017.
  2. Sondermann W, Zimmer L, Schadendorf D, et al. Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis. Medicine. 2016; 95(29):e4332.
  3. Willis BC, Johnson G, Wang J, Cohen C. SOX 10: a useful marker for identifying metastatic melanoma in sentinel lymph nodes. Appl Immunohistochem Mol Morphol. 2015; 23(2):109-12.
  4. Roebuck HL, Siegel MT. The ABCs of melanoma recognition. Nurse Practitioner. 2006; 31(6):11-13.
  5. Bristow IR, Berker DA, Acland KM, et al. Clinical guidelines for the recognition of melanoma of the foot and nail unit. J Foot Ankle Res. 2010; 3:25.
  6. Barnes BC, Seigler HF, Saxby TS, et al. Melanoma of the foot. J Bone Joint Surg Am. 1994; 76(6):892-8.
  7. Feibleman CE, Stoll H, Maize JC. Melanomas of the palm, sole, and nailbed: a clinicopathologic study. Cancer. 1980; 46(11):2492-504.
  8. Fortin PT, Freiberg AA, Rees R, et al. Malignant melanoma of the foot and ankle. J Bone Joint Surg Am. 1995;77(9):1396-403.
  9. Metzger S, Ellwanger U, Stroebel W, et al. Extent and consequences of physician delay in the diagnosis of acral melanoma. Melanoma Res. 1998; 8(2):181-6.
  10. Walsh SM, Fisher SG, Sage RA. Survival of patients with primary pedal melanoma. J Foot Ankle Surg. 2003;42(4):193-8.
Online Exclusives
Ronald Troxell, DPM, Jared Cicero, DPM, and Zachary Ogden, DPM
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