Classical Kaposi's Sarcoma Presenting in the Oral Cavity: A Case Report and Literature Review

Robert J. Martino, B.A., Carla Pulse, D.D.S., David J. Zegarelli, D.D.S.

Kaposi's Sarcoma of the "classic" type is a rare disorder, typically presenting itself with initial lesions on the extremities. Primary involvement of the oral cavity is an even rarer condition. A case is presented below of an elderly Jewish female with, to date, only solitary oral involvement of Kaposi's Sarcoma having neither evidence of HIV positivity nor a history of immunosuppressive therapy. The case illustrates that awareness of this possible manifestation of Kaposi's Sarcoma can aid in the diagnostic work-up of vascular lesions in the oral cavity . A brief review of the Kaposi's Sarcoma literature is also presented.

INTRODUCTION
In 1872, Moritz Kaposi, a Hungarian dermatologist, described odd skin tumors in five men in their sixth and seventh decades of life as "idiopathic multiple pigmented sarcoma of the skin."(26) Since these initial findings, four main types of Kaposi's Sarcoma (KS), also termed "multiple idiopathic hemorrhagic sarcoma", have been documented. The most common form, that associated with Acquired Immunodeficiency Syndrome, has been well documented since first described in the early 1980's. (13) This form appears in up to 40% of AIDS patients and may account for up to 90% of all cancers found in the AIDS population.(19) The African type, primarily found in regions of equatorial Africa is a much more common entity within its geographic setting, with findings of up to 9% of all malignancies in eastern Zaire.(24) While usually less severe than the AIDS-associated condition, the African-type is the only form known to regularly occur in children.(24) A third type of Kaposi's Sarcoma is that associated with patients on immunosuppressive therapy. As the practice of renal transplantation began in the 1970's, and the subsequent use of immunosuppressive therapy that is associated with it, the incidence of non African Kaposi's Sarcoma began to increase.(7) The course of this form of the disease is more variable, however reduction or cessation of the therapy can result in regression of the tumor.(19)

The fourth type of Kaposi's Sarcoma, the original type documented (8), is that which is covered in the case presented below. "Classic" Kaposi's Sarcoma is a rare condition. Primarily occurring in men of eastern-European (particularly Jewish) and Italian descent, the condition is rarely found in females.(25) While the patient in the case presented has an ethnic background consistent with classic KS, her gender makes the case unusual. Traditionally, the lesions have a general distribution, often appearing first on the limbs.(18) Oral involvement is a rare manifestation, occurring in approximately 11% of all cases described.(20) Initial oral involvement is an even rarer occurrence, with only fourteen cases previously documented.(1-3,8-10, 12, 14 16,18, 22, 23, 26) The case presented here is one of primary oral involvement of Kaposi's Sarcoma on the hard palate with no other signs of the condition in any other region of the body. The patient described is an elderly female of Jewish descent without a history of immunosuppressive therapy or AIDS. Due to the heightened awareness of Kaposi's Sarcoma's grim association with AIDS, its inclusion in the differential diagnosis can be often overlooked in the case of an HIV-negative individual.

Classic Kaposi's Sarcoma is typically a slowly progressing disease of older men with initial lesions usually appearing on the lower extremities. The multiple tumors that often appear cutaneously are not the result of true metastasis, but instead are multiple foci(20) The tumor rarely involves lymph nodes and responds well to radiation therapy. Classic KS may cause death, with the average duration of disease from diagnosis to death being eight years, as reported by O'Brien and Brasfield(16). Death from Classic KS itself is more the exception than the rule. Its slowly progressive nature leaves a long interval prior to metastasis. Patients that reach this stage of the disease usually die from gastrointestinal hemorrhage(12).

There has been evidence of an association of KS with second primary malignancies. Most often, patients with classic KS are at special risk of developing a malignancy of the lymphoreticular system(20). In a study done by Safai(21), 37% of KS patients had other primary malignancies.

The etiology of Kaposi's Sarcoma is still unknown. Friedman-Kien, et. al.(11) have suggested a genetic predisposition to the disease as a result of studies implicating increased incidence of the histocompatibility marker HLA-DR5 in 62% of classic KS cases. Windle-Taylor and Shah suggest an environmental etiology due to the overall geographical distribution of the disease(25). More recently, viral causes for KS have been explored. There has been some correlation between Cytomegalovirus antibodies found in the bloodstream and the incidence of classic, African, and HIV-related KS .(24) More recently, DNA sequences of a new human herpes virus were found in KS lesions of AIDS patients(6). A causal link between either Herpes virus or CMV and KS has not been thoroughly established.

While immunosuppression is highly associated with KS, it can not be considered an etiology. Immunosuppression is believed to create an environment that allows an opportunistic factor to cause KS. A causal model to explain the occurrence of KS has been developed by Wahman et. al..(24) Their cofactor model suggests that "the combined effects of numerous infectious agents, host factors, and environmental factors encourage KS proliferation."(24)

CASE REPORT

In May, 1995, an 86 year old white female of Jewish descent presented with a chief complaint of having lesions on the palate. Her past medical history was significant for a prosthetic aorta replacement and for carcinoma of the left kidney, which was treated with a left nephrectomy. Both surgeries were don one and a half years prior to the patient's first complaints about the palatal lesions. The patient had poor hearing and was legally blind. The rest of her history was non-contributory.

Clinical examination of the patient revealed the intraoral soft tissues to be within normal limits except for the area of the anterior right hard palate. In this area there were two purple/blue papillomatous-appearing exophytic lesions. One lesion measured approximately 0.5 cm in diameter and the second measured 0.2 cm. History regarding these lesions was non-contributory. The initial clinical differential diagnoses included the presence of two benign vascular lesions,

capillary hemangiomas, varices, etc., as well as possibly two papillomas having florid vascular components. These were the only such lesions found anywhere on the patient.

With local anesthesia and antibiotic prophylaxis, local excision of both lesions was completed. Microscopic examination of both displayed areas very consistent with KS. The smaller of the two specimens was an oval piece of soft tissue covered on one surface by benign appearing stratified squamous epithelium having overlying parakeratotic material. Beneath the epithelium, a well-defined zone of vascular tumor was evident. The tumor was composed of sweeping fascicles of slightly enlarged and spindle-shaped cells that ran in haphazard directions. There were numerous tiny vascular slits filled with extravasated red blood cells. Minimal mitotic activity was noted. The larger and more posterior of the two lesions had a similar histological appearance except for its surface. This specimen displayed soft tissue incompletely covered by a focally ulcerated layer of benign-appearing stratified squamous epithelium. Beneath the surface, acute and chronic inflammatory cells were evident along with the underlying vascular lesion. The diagnosis for both lesions was undeniably Kaposi's Sarcoma. As a result of these findings, the patient was HIV tested and asked about any history of immunosuppressive therapy. The patient tested negative for HIV and denied any immunosuppressive therapy. Her physician verified her medical history and found no evidence of extraoral KS lesions.

The patient returned for a three month follow-up examination. A clinical examination revealed two tiny exophytic blue/purple lesions of the right anterior palate in the same area of the two prior lesions. Under local anesthesia and antibiotic prophylaxis, both lesions were excised. The smaller specimen, present on the right palatal gingiva, had mild suggestion of KS. The larger lesion, found closer to the palatal midline, was diagnostic of KS. Despite our efforts, the patient has not returned for further follow-up examinations.

DISCUSSION

The awareness of oral Kaposi's Sarcoma as a diagnostic possibility can help in the work-up of vascular lesions in the oral cavity of non-immunosuppressed individuals. The non African, non-immunosuppressed, HIV-negative individual is rarely a candidate for oral KS. The tumor's strong association with AIDS and individuals on immunosuppressive therapy can cause one to overlook that KS existed long before AIDS and renal transplants.

The above mentioned case did not include KS in the initial clinical differential diagnosis. The rarity of solitary KS in an HIV(-) and non-immunosuppressed patient contributed to the absence of KS as a diagnostic possibility in the work-up of the patient. Clinically, the lesion can be confused with capillary hemangiomas, pyogenic granulomas or other benign vascular proliferations. Microscopically, in the early stages of the tumor's growth, the diagnostic spindle cell proliferation is not always evident. Therefore, it is also possible that a biopsy can be initially misdiagnosed as a benign vascular lesion.

The findings of lesions on the palate of the patient are consistent with the findings of Farman and Uys in that the most common site of intraoral KS is the palate, followed by the lips and tongue.(7)

Several different treatment methods have been used on KS patients, including surgical excision, radiation therapy, as well as systemic and intralesional chemotherapy. All have led to variable success rates, with reported recurrence after each method. This patient was treated with complete excision of the two lesions. This is the preferred method of treatment for small isolated intraoral lesions. For more extensive, coalescent lesions, radiation is the preferred method of treatment. The irradiation varies with the size and depth of the lesion.(17) Borock, et. al, suggest using more aggressive and extensive radiotherapy in the initial stages in an effort to stop the progression. (5) An alternate method of treatment of KS that has met with some success is intralesional chemotherapy. This method, found to be more successful than systemic chemotherapy, involves intralesional injection of either interferon or vinblastine.(6) Intralesional injections eliminate the risk of immunosuppression that can be associated with systemic chemotherapy. (6)

SUMMARY

Kaposi's Sarcoma is an unusual vascular neoplasm. Its etiology continues to be speculated upon and its behavior is sometimes unpredictable. In the past fifteen years, KS has come to be synonymous with AIDS. The tumor's existence as an individual entity has been shadowed by this association. Still, classic forms of KS exist and the clinician should be cognizant of the clinical manifestations of this subtype.

Intraoral manifestations of Classic KS, whether associated with generalized lesions or existing as the sole presentation of the condition, are extremeley rare findings. Since the first documented case of primary oral KS by Feit (8) in 1928, only fourteen similar cases have been reported. Of those fourteen, only six described a physical examination to confirm the absence of cutaneous lesions. (3,9,14,16,22,25) Interestingly, half of those cases also involved a female patient. Our paper represents the sixth reported case of well documented primary oral KS of the classic type without, to date, associated cutaneous lesions.

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