When A Patient Has Not Responded to Treatment for a Suspected Fungal Infection

A 59-year-old White male presented to the clinic due following failed treatment of a suspected right foot fungal infection. His past medical history included type 2 diabetes without complications, hypertension, and increased body habitus. He related no significant family history of skin lesions or malignancies. The patient had undergone several months of topical antibacterial and antifungal therapy, with no improvement noted. He presented to our clinic due to a referral following failed treatment of a persistent lesion. His complaint originally presented as a painless lesion of unknown origin without itching, burning, or drainage. No structural bony prominences were noted. He was initially treated for localized tinea pedis.

Per his history, the lesion initially appeared as a hyperkeratotic fissure to the plantar right fourth digital sulcus. Upon our examination, progressive medial and lateral erythematous superficial dermal eruptions extended to the third and fifth digital sulci, with no hyperpigmentation noted. The fissure was still present, which at the time of the encounter measured 1 cm x 0.2 cm x 0.1 cm (Figure 1). The patient did not experience any pain at the site. Due to the chronicity and recalcitrant nature of the lesion, we performed a 4-mm punch biopsy. There was localized hyperpigmentation with skin peeling. However, the lesion did not display significant edema, calor, malodor, or drainage. At the center of the lesion was a fissure against Langer lines with mild hyperkeratotic skin buildup that did not probe deep to capsule or bone. No digital deformities were noted superior to the lesion.

The biopsy results revealed a diagnosis of acral melanoma. We referred the patient to oncology, which recommended wide excision of the malignant lesion. He underwent this procedure under intravenous sedation in a hospital setting. The surgical excision involved an encompassing ellipse to the depth of the deep fascia. Closure of the site occurred primarily without issue. Review by the hospital pathologist and confirmed the diagnosis of malignant acral melanoma; however, they could not determine a specific categorization. The lesion was recorded as 2.9mm Breslow’s depth and pathology confirmed negative margins. The patient was immediately lost to follow-up, and did not keep appointments with either podiatry or oncology. No further specialized imaging or treatments were initiated at that time.

The patient returned to our clinic a year after the index procedure. Once again, he presented with a lesion on the right foot, seemingly a recurrence at the plantar fourth digital sulcus. Unlike originally, the lesion now presented with an increased granular base and adjacent hypopigmentation (Figure 2). There was no hyperkeratosis, but we did note surrounding maceration beneath the fourth digit. The lesion measured 2.2 cm x 1.2 cm x 0.1 cm at this encounter. Again, we referred the patient to oncology and the patient underwent another wide excision, this time with a concurrent inguinal node biopsy (Figure 3). The excision was again closed primarily (Figure 4). The postoperative pathology report confirmed malignant melanoma, superficial spreading type. The lesion showed evidence of invasion within the reticular dermis with Breslow’s thickness of 3mm and negative excisional margins. A right inguinal sentinel lymph node biopsy did not exhibit metastasis. A postoperative positron emission tomography (PET) scan revealed positive uptake at the popliteal lymph nodes. Surgical oncology performed a repeat sentinel node biopsy, this time popliteal, which was positive for 2 metastatic malignant melanoma tumors 2.5cm in size. The patient is currently undergoing chemotherapy per oncology. At the patient’s second and fourth week follow-ups, the surgical site was fully healed without complications or digital contractures.

Key Questions to Consider

1. What might one include in a differential diagnosis for this patient?
2. What history and exam findings might trigger one to perform a biopsy?
3. What is a vital component of the prognosis for this condition?

Answering The Key Diagnostic Questions

1. Tinea pedis, recalcitrant fissure or abrasion, verruca plantaris, fibroma, malignancy, structural deformity leading to pressure point (plantar plate tear, hypermobility of TMTJ)
2. Length of time associated with the presenting concern, evolving nature of the appearance of the lesion, and lack of response to other treatment.
3. Lesion depth largely determines prognosis.

What You Should Know About the Diagnosis

Melanomas account for 5% of skin tumors but have increased rates of metastasis and account for 80% of skin tumor-related deaths.¹ The incidence of pedal melanoma is between 3 and 15%.^2,3 Melanomas found on the extremities are described as acral melanomas. Melanomas of the lower extremity are uncommon and difficult to manage. These cases are complicated further by unusual visual manifestations that may not be immediately indicative of a malignant lesion.

It is important to distinctly note the terminology of acral melanoma. Acral melanomas are defined by their locations on the extremities, typically on hairless surfaces. One should not confuse this with acral lentiginous melanoma, which is a distinct histopathological classification of cutaneous melanoma.⁴ Confusingly, the World Health Organization (WHO) does not define the dorsal surfaces of the hands and feet as acral locations, which the literature commonly describes as such.⁵

Superficial spreading melanoma is a subgroup of melanoma and the most common cutaneous melanoma in the lower extremity in Western countries.⁶ A strong clinical suspicion should be held for concerning lesions of the plantar foot in Asian, African, and Latin populations as they have an increased incidence of acral melanoma.^3,7 Superficial spreading melanoma is typically confined to the epidermis, commonly found outside of volar skin, and does not necessarily correlate with cumulative sun damage.⁸ It initially starts with radial spread followed by an invasion via vertical growth. Depth is the most important prognostic factor in melanomas.^9,10 On evaluation, superficial spreading melanoma is likely to be asymmetric and ranging in pigmentation. However, amelanotic superficial spreading melanomas are rarely encountered and rarely reported.

To our knowledge, superficial spreading melanoma has yet to be described in the literature on the plantar foot surface. Tas and colleagues describe superficial spreading melanoma with an atypical presentation of an amelanotic nodular center more consistent with other melanomas.¹¹ Like this patient’s presentation, the histopathologic results were inconsistent with the clinical presentation. Regardless of diagnosis, prompt recognition of suspicious lesions is critical to prevent metastasis. Updated WHO guidelines reaffirm that histopathological analysis is the cornerstone for diagnosis.⁵ However, genetic analysis is becoming more commonly utilized for more precise diagnosis.

Most podiatric physicians are familiar with grading suspicious lesions based on the acronym ABCDE (asymmetric shape, border, color, diameter, evolution). However, the use of ABCDE can easily break down in the absence of pigmentation. The addition of the acronym CUBED (colored, uncertain diagnosis, bleeding, enlargement or ulceration, delay in healing beyond 2 months) can apply in the setting of foot lesions.¹² Although patient nonadherence was an issue, earlier recognition prior to the referral to our practice may have changed the trajectory of his disease.

After initial diagnosis, treatment of melanoma in the foot is challenging due to the need for adequate excision while remaining functional outcomes. Luckily, our patient’s lesion was in an area favorable for uncomplicated closure. A variety of options are available, from primary closure to biologics and local pedicle flaps.¹³ Careful planning and procedural selection are a necessity for treatment. Comprehensive treatment of foot melanomas requires a team approach from primary care physicians, surgical and nonsurgical oncologists, dermatologists, and podiatrists.

Dr. Ferryanto is a Podiatric Medicine and Surgery Resident at Ascension Health Saint Joseph Hospital in Chicago.

Dr. Palmieri is an Attending Podiatric Medicine and Surgery Physician at Ascension Alexian Brothers in Elk Grove Village. He is a Fellow of the American College of Foot and Ankle Surgeons and the American College of Podiatric Medicine.

References

1. Bichakjian CK, Halpern AC, Johnson TM, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011;65:1032-1047.
2. Tseng JF, Tanabe KK, Gadd MA, et al., Surgical management of primary cutaneous melanomas of the hands and feet. Ann Surg. 1997;225(5):544–553.
3. Lee HY, Chay WY, Tang MB, et al. Melanoma: differences between Asian and Caucasian patients. Ann Acad Med Singapore. 2012;41:17–20.
4. Bernardes SS, Ferreira I, Elder DE, et al. More than just acral melanoma: the controversies of defining the disease. J Pathol Clin Res. 2021;7(6):531-541.
5. Elder DE, Bastian BC, Cree IA, et al. The 2018 World Health Organization classification of cutaneous, mucosal, and uveal melanoma: detailed analysis of 9 distinct subtypes defined by their evolutionary pathway. Arch Pathol Lab Med. 2020;144:500–522.
6. Crowson AN, Magro CM, Mihm MC. The Melanocytic Proliferations. (2nd ed) John Wiley & Sons:2014.
7. de Vries E, Sierra M, Piñeros M, Loria D, Forman D. The burden of cutaneous melanoma and status of preventive measures in Central and South America. Cancer Epidemiol. 2016;44 Suppl 1:S100-S109.
8. Bobos M. Histopathologic classification and prognostic factors of melanoma: a 2021 update. Ital J Dermatol Venerol. 2021;156(3):300-321.
9. Nunes LF, Mendes GLQ, Koifman RJ. Sentinel lymph node biopsy in patients with acral melanoma: analysis of 201 cases from the Brazilian National Cancer Institute. Dermatol Surg. 2019;45:1026–1034.
10. Bello DM, Chou JF, Panageas KS, et al. Prognosis of acral melanoma: a series of 281 patients. Ann Surg Oncol. 2013;20:3618–3625.
11. Tas B, Ozen A, Caglar A. Amelanotic nodular appearance within superficial spreading melanoma. J Cosmet Dermatol. 2022;21(9):3949-3953.
12. Bristow IR, de 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.
13. Ruffolo AM, Sampath AJ, Kozlow JH, Neumeister MW. Melanoma of the hands and feet (with reconstruction). Clin Plast Surg. 2021;48(4):687-698.