Classic Solitary Kaposi Sarcoma of the Foot in an Immunocompetent Patient: A Case Report

Kaposi sarcoma (KS) is a tumor derived from endothelial cell lineage caused by Kaposi sarcoma-associated virus or human herpesvirus-8. The authors have set forth to describe a unique presentation of the classical form of KS in a homosexual individual. The authors demonstrate that a full history and physical are important in determining how to guide treatment along with ancillary tests, which can prove vital to determine management strategy. The authors then provide a brief discussion about variants of KS, biopsy techniques, and current treatment options available to patients diagnosed with this condition. The patient described is a 60-year-old male of Eastern European descent, who is immunocompetent in a monogamous homosexual relationship with a new onset and rapidly progressing skin lesion on the plantar aspect of his foot. Surgical excision of the tumor was performed and surveillance was determined to be the treatment of choice.

Kaposi sarcoma (KS) is a vascular tumor derived from the endothelial cell lineage caused by Kaposi sarcoma-associated virus (KSHV), also known as human herpesvirus-8 (HHV-8). It represents about 1% of all diagnosed cancer cases worldwide.^1,2 Five subtypes of KS have been described: classic KS, African endemic KS, immunosuppression-associated KS, AIDS-associated KS, and nonepidemic gay-related KS.^1-5 More than 95% of the lesions have been found to be infected with HHV-8, regardless of the clinical subtype.⁶ Classic KS usually occurs in elderly men from the Mediterranean region. It is a chronic, slowly progressing disorder, usually confined to the skin, which only rarely affects other organs.⁷ Nonepidemic gay-related KS is associated with homosexual males and has a similar presentation to classic KS, but has several distinct characteristics including lesions occurring most frequently on the extremities and genitalia, and new lesions occurring every few years.^8,9 The authors present a case study of a classic KS in a homosexual male who is HIV1/2 antibody negative, discovered as a solitary mass which was a rapidly growing skin lesion on the plantar midfoot at a large academic institution.

The authors report the case of a 60-year-old male patient who presented to the Podiatry Clinic at the University of Michigan Hospital and Health Systems, Ann Arbor, MI with a solitary raised, pedunculated mass on the plantar aspect of his right foot (Figure 1). He reported that the lesion grew rapidly over the course of 1 week and was beginning to interfere with his ambulation. He denied a significant family history of skin lesions and had a past medical history significant for gastroesophageal reflux disease, hypothyroidism, hypertension, and hyperlipidemia. The patient denied smoking and illicit drug use, occasionally drank alcohol, and was involved in a long-term monogamous homosexual relationship. The patient’s last negative HIV test was in 2008 and repeat testing performed in 2015 was again negative. The patient, a physician by vocation, routinely performed skin examinations on himself for suspicious changes. His review of systems was negative. 

The mass, approximately 1.5 cm in length (measured from medial to lateral) by approximately 1.0 cm (measured from anterior to posterior), was red-to-violaceous in color with 2 lobules attached to the skin medially by a stalk. There was significant venous congestion noted to the entire arch. There was significant bleeding upon mechanical irritation of the mass. Surrounding the mass, the medial aspect of the plantar arch was purple with venous congestion that was blanchable and dependent in nature.  There were no other visible primary or secondary skin changes on his foot, leg, or thigh.  There was no lymphadenopathy. Differential diagnosis included eccrine poroma, angioma, pyogenic granuloma, melanotic melanoma, arteriovenous malformations, among other vascular proliferative lesions. 

After discussion about the lesion and considering its rapidly occurring nature, an excisional biopsy was performed in the office on the same day under local anesthesia. Informed consent was obtained. The surrounding skin was prepped and draped in standard aseptic technique and an injection of 1% lidocaine was utilized with dilute epinephrine (1:200,000 dilution) to aide in hemostasis. The pedunculated mass did not have any attachments to underlying skin laterally. Excisional biopsy was therefore planned in standard 3:1 length to width ratio utilizing 2 semi-ellipses with approximately 4-mm margins planned circumferentially about the stalk of the lesion.  The lesion, including subcutaneous tissue, was excised in toto and the base of the wound was cauterized with electrocautery for hemostasis. It was allowed to close by secondary intention because of pre-biopsy venous congestion. Bleeding occurred during excisional biopsy with approximately 5 mL of blood loss. The specimen was passed off the field into a 10% formalin specimen cup and was sent for anatomic pathology for identification.

Pathology
The dermatopathologist described the  lesion as a pink-tan to red-brown ragged and irregularly shaped soft tissue mass. It measured 1.9 cm x 1.5 cm x 1.3 cm covered partly in a blood clot. It was identified as KS and immunohistochemical stains for HHV-8 and ETS-related gene (ERG) were both positive in neoplastic cells, confirming the diagnosis of KS. 

Histology
Hematoxylin and eosin (H&E) stains, high and low magnification of skin lesions respectively are shown in Figure 2. Classic KS demonstrates a dermal nodule (Figure 2A) with dermal proliferation comprised of a spindle cell proliferation (Figure 2B) of endothelial cells forming sinuous vascular spaces. Upon higher magnification, this pattern has been likened to schools of fish. This can be appreciated especially on the left aspect of the high magnification H&E stain. Figure 2 demonstrates the use of an antibody to HHV-8 to confirm diagnosis. The antibody to HHV-8 latent nuclear antigen 1 (brown) is a highly specific commercial stain and has simplified the diagnosis in difficult cases. The antibody is quite reactive to the specimen (Figure 3). 

Treatment
Following excisional biopsy with circumferential 4-mm margins about the stalk and the resultant KS diagnosis, the patient was referred to the Podiatry Clinic at University of Michigan Hospital and Health Systems (Ann Arbor, MI). The biopsy site healed within 3 weeks of the biopsy. At the sarcoma clinic, the patient was determined to not have any other skin lesions suspicious for KS. Due to the lack of additional suspicious skin lesions, the oncologist at this time deferred treatment and placed the patient under surveillance following complete resection, albeit with possible positive skin margins. The plantar aspect of the involved foot healed unremarkablely following a single excisional biopsy treatment. The patient’s discomfort and venous congestion also completely resolved within 2 weeks following the single complete excision of the lesion. The patient is now 6 months beyond the date of excision and no recurrence has been noted (Figure 4).

Of all diagnosed cancer cases worldwide, 1% are KS.^1,2 There are 5 subtypes of KS including: classic KS, African endemic KS, immunosuppression-associated KS, AIDS-associated KS, and nonepidemic gay-related KS.^1-5,10 The variety and prevalence of each subtype of KS depends largely on the population. For instance, classic KS occurs primarily in elderly men of Eastern European or Mediterranean origin,¹ and the male predominance of classic KS diagnosis is almost 10:1.¹ Meanwhile, in immunosuppression-associated KS, the incidence of KS in solid organ recipients is about 500 times than that found in the general population.⁴ Patients with AIDS-associated KS are subject to multiple neoplasms, but KS accounts for most of them.⁵ Prior to the AIDS epidemic, there was only about 2 new cases of KS found for every million people in the United States each year.^5,8 During the AIDS epidemic, the rate of KS in this country increased more than 20 times, peaking at about 47 cases per million people per year in the early 1990s.^8,11 Because of new treatments for AIDS, KS has become less common in the United States, and it now occurs at a rate of about 6 cases per million people each year.^8,12 Therefore, the likelihood of having KS largely depends on the patient’s medical history and demographic data. In the presented case, the patient is a middle-aged, white male of Eastern European descent with a primary rapidly occurring solitary lesion. Although he is a homosexual male, his lack of prior mass and rapid occurrence does not coincide with case reports on non-epidemic gay-related KS.    

Traditionally, 3 types of biopsy techniques are available when faced with a soft tissue tumor or abnormal skin lesion: excisional, incisional, and core needle. Excisional biopsies are ideally utilized when removal of the entire lesion is reasonable. Punch biopsy, shave biopsy, and sauceratization are well described in the literature.¹¹ It is recommended that skin lesions for excisional biopsy techniques be smaller than 3 cm because of ideal length to width ratios of 3:1 to reapproximate skin for closure. Clinicians also must remember that while saucerization and shave biopsy techniques offer information about the lesion above the surface of the skin, estimating depth of tissue invasion from these techniques are their greatest limitation. Punch biopsy, however, allows for adequate depth to be obtained when removing the lesion, but it may not allow for removal of the entire lesion, depending on its size.¹³ Common available punch biopsy sizes are 2–8 mm, with a punch biopsy larger than 4 mm requiring a suture for appropriate hemostasis and skin reapproximation.¹³

Incisional biopsy allows for removal of only part of the lesion for pathological evaluation. This technique works when the lesion is too large to excise in toto with excisional biopsy or when there are multiple lesions that need to be evaluated.¹⁴ It is desirable to obtain at least part of the lesion and margins that are normal in appearance for comparison under microscopy. It is important to remember that if the skin lesion of interest is suspected to be an inflammatory condition, the skin that appears most active is best for sampling.¹³ Because only a small sample is taken, this inherently is the limitation of the incisional biopsy technique. 

Finally, fine needle aspiration uses a small hollow needle to obtain cells for evaluation. A core needle biopsy is similar in that it removes more tissue from the lesion, not just the cells within the lesion.¹³

Treatment usually depends on the type of lesion present and whether there is a solitary lesion or multiple lesions. These treatments are based largely on the extent of involvement of skin, lymph nodes and mucosa, and status of the immune system. In general, for patients with a single lesion, excisional biopsy is usually a definitive option.¹⁵ An alternative to excisional biopsy includes cryotherapy, topical retinoid treatment (ie, alitretinoin), curettage and electrodessication, radiation therapy, photodynamic therapy, and intralesional chemotherapy.⁸ In the treatment of this patient, an attempt was made to obtain clean margins through excisional biopsy, but this approach failed in practice. Prompt identification of the suspicious lesion did allow for a higher level of care to be established and a comprehensive plan created. Lack of clean margins does not always necessitate further surgery because observation is a viable option, especially with solitary lesions in immunocompetent patients. However, multiple excisions may be a reasonable approach to achieve good control of the disease if recurrence is local. To date, there is no recurrence, and reepithelialization has been visualized in this patient. 

In patients with extensive KS, disease can be managed using chemotherapy or radiation if the disease is limited to the skin with or without superficial lymph node involvement. A liposomal anthracycline, such as pegylated liposomal doxorubicin and daunorubicin, is usually a first-line therapy,¹⁶ and a taxane, either paclitaxel or docetaxel, is used as second-line therapy when required.^17-19 New treatment methods include topical use of imiquimod, angiogenesis inhibitors, thalidomide, and other immunomodulating agents.²⁰ Ongoing HIV vaccines may have a particular use in AIDS-related KS. As most KS types are associated with HHV-8, this has become a new target for KS drug development and biologic therapy.^20-26 

In this patient’s case, excisional biopsy was chosen for diagnostic and therapeutic reasons because of the solitary and small (less than 3 cm in size) nature of the presenting lesion. While clean margins were not obtained, complete resolution of the skin abnormality was demonstrated and surveillance was undertaken as a definitive treatment plan by a multispecialty team. Because of the patient’s education as a medical professional, his vigilance was a critical aspect to determine the necessity of other treatments. His training aids in selecting surveillance as a treatment option, but resolution and lack of other lesions make this a reasonable treatment plan.   

To date there has been no recurrence. This was a 6-month period of local surveillance by the biopsy-performing physician, primary care physician, and patient. The excisional biopsy site remains clinically clear and with complete reepithelialization, as was the case within 6 weeks of the original procedure. There remains no pain with ambulation and the patient is otherwise doing well. The classic form of KS is usually a chronic, indolent disorder, slowly progressing over a period of several years or decades. The uniqueness of this case is the rapid progression of the tumor and the solitary and papulosquamous eruptive nature in a nonheterosexual male with immunocompetent status. Secondarily, there has not been recurrence anywhere on the patient’s body since the initial excisional biopsy was performed. With thorough history and patient work-up, the KS was biopsied without delay and appropriate referral to an oncologist was obtained in an expeditious manner. It remains important to have a high index of suspicion of KS with a rapidly expanding primary skin lesion on the plantar surface of the foot so appropriate care can be obtained for the patient.    

Affiliations: University of Michigan Hospital and Health Systems, Department of Internal Medicine, Division of Metabolism, Endrocrinology, and Diabetes, Ann Arbor, MI

Correspondence:
Brian M. Schmidt, DPM
Domino’s Farms
(Lobby C, Suite 1300)
24 Frank Lloyd Wright Drive
Ann Arbor, MI 48106
bmcs@med.umich.edu

Disclosure: The authors disclose no financial or other conflicts of interest.