Differentiating Non-Pigmented Tumors In The Lower Extremity

Tracey C. Vlahovic, DPM

Given the high stakes in diagnosing potentially dangerous lower extremity tumors, having a clear idea of the clinical presentation is vital. This author uses several case studies to demonstrate the effective diagnosis and treatment of non-pigmented tumors.

   Flesh colored lesions anywhere on the body can pose a diagnostic challenge. They typically are the “zebras” in a field of horses. In other words, they are uncommon but one should think of them on a regular basis when a lesion presents as unusual or not responding to common therapies.

   On the lower extremity, a delay in diagnosis for a lesion such as amelanotic melanoma can be devastating for both the patient and practitioner. This article will address both benign and malignant non-pigmented tumors of the lower extremity.

What You Should Know About Dermatofibromas

   Dermatofibromas, which most commonly occur on the lower extremities, are flesh-colored, dome-shaped papules or nodules that are firm to the touch.1 They can occasionally be pigmented but often will be tan to pink. Pinching them in toward their center will cause them to umbilicate (i.e. the “dimple sign”).2 These lesions typically occur on the anterior tibia in females and are usually asymptomatic. Patients have reported pain, making dermatofibromas the most painful of skin lesions when this does occur.3 The patient may complain that the site was originally an insect bite or a cut, but in reality, a dermatofibroma’s origin is truly unknown.

   Histologically, dermatofibromas are a nodular proliferation of fibroblasts in the reticular dermis with overlying hyperplasia of the epidermis.1 Clinically, they may resemble a scar, a keloid or the malignant dermatofibrosarcoma protuberans and nodular Kaposi’s sarcoma. Dermatofibromas are usually solitary lesions but they can also occur in clusters in patients who are immunocompromised.

   Treatment consists of complete excision or leaving the lesion alone. Due to the lesion’s typical location of the anterior tibia and the scarring potential there, most physicians opt to excise only if clinical signs and symptoms warrant it. In this case, the scar can be worse cosmetically than the original nodular lesion. However, some patients prefer the scar over the original protrusion.

Inside Insights On Fibromas

   Fibromas, also known as cutaneous angiofibromas, are firm, smooth skin-colored exophytic columns that usually extend from the nail unit. If present dorsally on the nail plate, fibromas will cause a vertical depression in the nail plate that can reverse once one removes the lesion. Fibromas can also arise plantar to the nail plate at the hyponychium. One would see solitary lesions in adults. Multiple lesions (called Koenen’s tumors) in and around the nail unit at puberty are linked to tuberous sclerosis. Differential diagnoses include verrucae, skin tags and nevi.

   Treatment of the problematic fibroma typically consists of excision although recurrence rates are high. Researchers have described treatment with both electrodesiccation and a CO2 laser post-excision, but the nail plate and surrounding tissue may be damaged with these modalities.4 Application of phenol to the area of the excised fibroma has been a successful treatment both cosmetically and clinically.4 One simply shaves the fibroma and applies phenol without removing the nail plate, thus protecting the nail matrix.

How To Treat Digital Mucous Cysts

   Digital mucous cysts (cutaneous myxoid cysts) occur on the dorsal surface of the distal phalanx and ultimately result in a longitudinal depression in the nail plate.5 Differential diagnoses to consider are: fibroma, rheumatoid nodule and giant cell tumor of the tendon sheath. The etiology is unknown and pain is uncommon in most cases.

   One can attempt transillumination with a penlight to distinguish the cyst from a giant cell tumor. However, a preoperative ultrasound or MRI will prove more useful.6 Of course, researchers have described numerous excisional methods, such as needling the lesion, injecting it with corticosteroids and cold steel excision.

   When it comes to recalcitrant and recurrent tumors, a satisfactory treatment method is one that includes partial excision of the proximal nail fold with healing by secondary intention.7

   A 43-year-old female with a history of gout presented for a second opinion of a painful cyst on the dorsum of her left second toe. It was present 3 mm from her cuticle. Her previous physician had injected the cyst with steroids and had tried to evacuate the fluid from the cyst with no relief. The doctor had also “removed” the cyst at one point in the office but the patient did not remember having stitches. The lesion was recurrent and the patient wanted it removed.

   In the OR, the surgeon excised the lesion and 1 mm of surrounding proximal nail fold in toto. There was no connecting stalk to the tendon sheaths or joint plantarly. The pathology report returned as a cutaneous myxoid cyst. The patient healed uneventfully and there has been no recurrence of the lesion six months after the procedure.

Pertinent Pearls On The Various Types Of Porokeratosis

   The term porokeratosis in the podiatric field usually denotes a solitary pitted lesion (porokeratosis plantaris discreta). However, in the dermatology world, the term describes a lesion that has a specific histologic finding via biopsy: the cornoid lamella.8 The cornoid lamella is a wall of parakeratosis, which correlates to the raised border one would see around these lesions clinically. Also bear in mind that researchers have described malignant transformation of these lesions into squamous cell carcinoma in all types of porokeratosis.9

   The clinical variants of porokeratosis are: porokeratosis of Mibelli (PM), disseminated superficial actinic porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata (PPPD), linear porokeratosis and punctate porokeratosis.

   Porokeratosis of Mibelli begins in childhood as a brown to pink skin colored papule that extends into a plaque. Classically, a thin keratotic border surrounds this plaque and the center of the lesion may become atrophic. It is usually unilateral and tends to affect the extremities.

   Disseminated superficial actinic porokeratosis occurs on the legs bilaterally and symmetrically, but spares the plantar feet. It presents as small pink to flesh-colored pruritic papules. It is questionable if they are truly ultraviolet-induced but they often resemble and coexist with actinic keratoses. True DSAP will involve only the legs while DSAP and actinic keratoses will also involve lesions on the face.

   Porokeratosis palmaris et plantaris disseminata is a smaller version of PM but has less keratosis and typically occurs on the palms and soles. Linear porokeratosis begins in childhood, appears usually as one plaque on the extremity and is rare. Punctate porokeratosis occurs on the palms and soles commonly during puberty or adulthood.

   Differential diagnoses include punctate keratoderma, verrucae, “seed corns” and keratosis punctata palmaris et plantaris of the instep, which commonly occurs in the African-American population. None of the above differentials have a cornoid lamella histologically. Accordingly, one cannot place them in the category of porokeratosis.

   The reason for malignant transformation into squamous cell carcinoma is unknown but it occurs more frequently in older patients and older lesions. Treatments are meant to be destructive and curative. These treatments include: cryotherapy, topical 5-fluorouracil (Efudex, Valeant Pharmaceuticals), excision, curettage and CO2 laser.10 All have varying success and, of course, one should tailor treatment to the patient’s situation.

Why The Presence Of Verrucae Can Be Deceptive

   The cutaneous manifestation of human papillomavirus (HPV) infection, verruca, poses an annoyance to most patients and practitioners due to its stubborn nature. Both plantar and flat verrucae appear as flesh colored interruptions in the geography of the skin. Flat or plain verrucae may also be confused with lichen planus. However, the lacey white pattern of Wickham’s striae within the lesions of lichen planus should alert the practitioner.11 Hyperkeratotic lesions, punctate porokeratosis, hyperhidrotic pitting with pitted keratolysis, and the association of amelanotic melanoma with the nail may be confused with plantar verrucae.

   Long standing cauliflower-like lesions that do not respond to typical verruca treatments or are fungating or draining should alert the physician to the possibility of malignancy.

   A 67-year-old man with a history of melanoma on his chest presented with a 20-year-old lesion on his plantar foot. His podiatric physician had been treating the lesion as verruca with salicylic acid and cryotherapy with no change. The patient presented in the clinic with a lesion that was non-pigmented, fungating, malodorous and draining.

   The patient underwent an incisional biopsy in the office. The pathology results revealed squamous cell carcinoma. The patient went to the OR for a full excision and received follow-up by oncology.

   In his case, a previous personal diagnosis of melanoma warranted a deeper look into his fungating lesion. Patients who have had a previous non-melanoma skin cancer or melanoma skin cancer have almost a 60 percent chance of developing a second skin cancer.12

   A 70-year-old female with a history of diabetes, gout, hypertension and peripheral neuropathy had been treated for a verruca on the lateral side of her foot for several years with no change. She presented with a cauliflower like lesion that was draining a milky-like fluid on the lateral aspect of her foot proximal to her fifth digit.

   An incisional biopsy revealed a verrucous carcinoma. Further surgical care included amputation of the fifth digit, resection of the fifth metatarsal and surrounding skin. The verrucous carcinoma had invaded the bone and the physician noted resulting osteomyelitis. All margins were clear and the wound healed uneventfully. The patient received follow-up by oncology.

How To Diagnose And Treat Amelanotic Melanoma

   Melanoma is characterized by clinical variegation in pigment: blue, black, red and white. However, the more deadly and rarer form of melanoma is amelanotic due to its lack of easily recognizable signs, which ultimately lead to a delay in diagnosis. Amelanotic melanoma lacks most pigment but may have a small lentigo (pigmented lesion) nearby that can serve as a clue to the astute practitioner. As in the case with any suspicious lesion, the ABCs of melanoma can be a starting point for diagnosis and treatment.13

   B=border irregularity
   C=color variegation (red, white, blue within the lesion)
   D=diameter. Is it larger than a pencil eraser?
   E=evolution. This is especially important for a lesion that is amelanotic. How has it changed or how is it different from other lesions on the body?

   I also add an F for family or personal history of melanoma or other skin cancer.

   When it comes to the lower extremity, researchers have reported numerous cases of amelanotic melanoma.

   Gosselink and colleagues reported a rapidly growing and ulcerated red mass at the hallux in a patient with a family history of melanoma that was eventually diagnosed as subungual amelanotic melanoma.14 In this patient, differential diagnoses would include: verruca, chronic paronychia and pyogenic granuloma. The evolution of the lesion (i.e. rapid growth over one month) tipped the authors to be proactive surgically.

   Additionally, researchers have reported other amelanotic podiatric cases. An enlarging, lobulated mass on the heel and chronic non-healing plantar ulcer are just two lesions that mimicked verruca, pyogenic granuloma, neuropathic ulcer, foreign body granuloma and cavernous hemangioma.15 Due to this, amelanotic melanoma is known as the “great masquerader” and should be among the differential diagnoses when one is faced with an unusual and atypical lesion.16

   In addition to amelanotic melanoma, physicians should consider diagnoses of nonpigmented basal cell carcinoma and squamous cell carcinoma. One should suspect a non-healing, red scaly lesion of being malignant in the appropriate clinical scenario.

   For example, a 52-year-old female presented for a second opinion with her hallux nail partially removed and sanguinous drainage. She reported no pain or discomfort. However, she related that every time she ran on her treadmill, her hallux toenail would bleed. Her previous physician told her to stop running on the treadmill and trimmed the nail to relieve any pressure. During her visit, she underwent an excisional biopsy. Pathology reported a diagnosis of squamous cell carcinoma and the patient got a referral to a Mohs surgeon for appropriate follow-up surgical care.

In Conclusion

   Overall, the above lesions can prove to be a diagnostic and therapeutic challenge. It is important for the podiatric practitioner to be proactive in obtaining a thorough history and performing a skin biopsy when warranted.

Dr. Vlahovic is an Associate Professor at the Temple University School of Podiatric Medicine in Philadelphia. She is a Fellow of the American Professional Wound Care Association (APWCA).


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