Spontaneous Regression of Oral Kaposi Sarcoma in an HIV Negative Male

Abstract

Oral Kaposi sarcoma is a slowly progressing, HHV-8 related angioproliferative disorder strongly associated with immunosuppression. Regression can occur with treatment. We present a 49-year-old HIV-seronegative Caucasian male individual with two rapidly enlarging OKS lesions that spontaneously regressed and completely resolved without treatment after a few months. The individual was under treatment with valacyclovir for herpes simplex infection and was receiving emtricitabine/tenofovir for HIV pre-exposure prophylaxis. Only the mandibular lesion was biopsied, revealing classic endothelial spindle cell proliferation with formation of slit-like spaces and multiple newly formed vessels. Nuclear HHV-8 was immunohistochemically confirmed. Serologic tests prior to and after the development of OKS did not reveal HIV infection. Emtricitabine/tenofovir prophylactic treatment may have contributed to the remission and resolution.

Kaposi sarcoma (KS) is a slow-growing vascular proliferation caused by human herpesvirus 8 (HHV8). Four nosologic types are described; classic KS (cKS), endemic/African KS, iatrogenic (transplant-related) KS (TKS), and epidemic/AIDS-related KS (AIDSKS). AIDSKS is considered the most common and aggressive type suggesting a synergistic relationship between human immunodeficiency virus (HIV)-1 and HHV-8.

We report a 49-year-old, HIV-negative, Caucasian male presenting with a fast-enlarging purple, multilobular lesion on the left anterior mandibular gingiva measuring 1.5 cm x 2.5 cm (Fig. 1A). A second lesion with similar appearance was identified on the right maxillary gingiva (Fig. 1B). Medications included valacyclovir for herpes simplex infection, and emtricitabine/tenofovir for HIV pre-exposure prophylaxis. Incisional biopsy of only the mandibular lesion revealed proliferation of endothelial cells featuring round, ovoid or spindle nuclei, eosinophilic cytoplasm and indistinct cytoplasmic borders, that formed sheets, small vessels or lined slit-like spaces with extravasated red blood cells (Fig. 2A). Endothelial cells were positive for HHV8 immunohistochemical stain (Fig. 2B). No other cutaneous lesions were identified, and CT and PET did not reveal any lesions. Serological testing for HIV infection was ordered and was again negative. Although treatment options were discussed, it was decided to delay treatment and just keep the individual on close surveillance intervals. In the next few weeks, both gingival lesions began to regress in size, and at four months they were almost completely resolved (Fig. 3). After 32 months there has been no evidence of recurrence or development of new lesions.

Fig. 1.

(A) Multilobular purplish nodule on the left side of the mandibular gingiva. (B) Slightly purplish papular lesion on the right side of the maxillary gingiva

Fig. 2.

(A) Endothelial cell proliferation characterized by cells with round, ovoid or spindle nuclei, eosinophilic cytoplasm and indistinct cytoplasmic borders. The cells formed sheets, small vessels or lined slit-like spaces with extravasated red blood cells. (B). Endothelial cells disclosed positive nuclear staining with HHV8 antibody

Fig. 3.

The mandibular lesion was almost completely resolved at 4 months

Controversy exists regarding KS definition as a true neoplasm or hyperplasia, or perhaps progression from an early hyperplastic process to a true sarcoma [1]. Although there is near 100% association with human herpesvirus 8 (HHV-8), it is thought that infection with HHV-8 is not sufficient to cause KS, and healthy individuals may be able to functionally limit progression of the virus to disease. Host immune dysfunction, genetic factors, and environmental factors likely play contributory roles [2]. Saliva has demonstrated higher copy numbers of HHV-8 than other bodily fluids. The oral cavity appears to be the primary portal of entry, with oropharyngeal epithelial cells exposed to HHV-8 facilitating replication. Thus, transmission of HHV-8 via mucosal shedding may explain its increased seroprevalence in men who have sex with men (MSM). The individual presented herein satisfies criteria for the recently and increasingly recognized new and 5th subtype of KS referred to as non-epidemic variant seen in MSM [3]. Only 1/72 individuals reported presented with oral lesions. This subtype has a better prognosis, and lesions are often limited to a single location [4].

Most cases of KS are treated with radiotherapy or chemotherapy. Reports of regression or remission of KS is associated with restoration of immunocompetence, with complete spontaneous remission reported in only 2–4% of cases [5]. Table 1 includes oral KS cases we were able to identify, regardless of the type, that regressed, and the treatment method in each one. In the present case, emtricitabine/tenofovir prophylactic treatment may have contributed to the remission and resolution.

Table 1.

Reported oral KS cases, regardless of type, that featured regression, and the reported treatment method

Case	Sex	Age	Location	Duration (in months)	KS type	Treatment	HIV status	Additional information	Reference PMID
1	M	5	Left palatal ridge	NA	Iatrogenic	Chemotherapy	Negative	History of acute lymphoblastic leukemia/Complete resolution	36329498
2	M	28	Gingiva, palate	3	Classic	Radiotherapy	Negative	Complete resolution	31,565,993
3	M	50	Gingiva, face, arms and torso	5	AIDS-related	Antiretroviral therapy and surgical excision	Positive	Left mandibular tumor was excised/no more information	30,601,874
4	M	49	Hard palate	1	AIDS-related	Antiretroviral therapy and surgical excision	Positive	Complete resolution	30,552,825
5	M	39	Palate and gingiva	3	AIDS-related	Radiotherapy	Positive	Complete resolution	14,682,665
6	M	35	Mucogingival junction, maxillary	2	NR	Surgical excision	Negative	Complete resolution	31,959,404
7	M	80	Hard and soft palate	NA	NR	Radiotherapy	Negative	Complete resolution	28,725,131
8	M	55	Maxilla	1	Iatrogenic	Chemotherapy (Everolimus)	Negative	History of liver transplantation/Complete resolution	28,708,648
9	M	27	Gingiva, hard palate	8	AIDS-related	Antiviral therapy (Zidovudine)	Positive	“Homosexual”/Gingiva-complete resolution	2,527,052
10	F	38	Palate, gingiva	8	Iatrogenic	Immunosuppressive drug (Sirolimus)	Negative	Pulmonary metastasis, CMV positive/Complete resolution	20,529,483
11	M	34	Gingiva, skin abdomen, foot	4	AIDS-related	Surgical excision and antiretroviral therapy	Positive	Complete resolution	18,978,711
12	M	23	Palate, buccal gingiva	NA	AIDS-related	Retroviral therapy	Positive	Complete resolution	18,978,711
13	F	76	Tongue	6	NR	Radiotherapy	Negative	Complete resolution	17,614,259
14	F	21	Mandible	4	Iatrogenic	Chemotherapy	Negative	History of renal transplant/Complete resolution	21,872,483
15	F	71	Hard palate		NR	Chemotherapy	Negative	Complete resolution	17,767,100
16	M	46	Lip, leg, toe	3	NR	Radiotherapy	Negative	Good response/Patient died for pulmonary tuberculosis	17,767,100
17	M	53	Tuberosity of the maxilla	NA	NR	Erythromycin/ Biopsy	Negative	“Homosexual”/Complete resolution	15,537,468
18	M	30	Maxilla (intraosseous), cutaneous lesions	< 1	AIDS-related	Chemotherapy (vinblastine)	Positive	Complete resolution	7,532,218
19	F	24	Palate	1	NR	Surgical excision	Negative	Complete resolution	13,431,211
20	M	32	Tuberosity, buccal mucosa, palate	6	AIDS-related	Tenofovir, lamivudine and efavirenz	Positive	Complete resolution	23,881,519
21	M	36	Alveolar ridge and palate	NA	AIDS-related	Antiretroviral therapy	Positive	Complete resolution	30,711,137
22	F	30	Tongue	4	NR	Surgery	Negative	History of pemphigus vulgaris/Complete resolution	22,135,617
23	F	86	Hard palate	12	NR	Radiotherapy	Negative	Complete resolution	2,212,159
24	M	28	Gingiva, palate	3	NR	Radiotherapy	Negative	Hepatitis B positive/Complete resolution	31,565,993
25	M	71	Parotid gland	3	NR	Surgery	Negative	Complete resolution	19,579,875
26	M	35	Hard palate and lower extremities	12	AIDS-related	Antiretroviral therapy (ritonavir and zidovudine)	Positive	“Homosexual”/Complete resolution	9,692,061
27	M	34	Palate, maxillary sinus and nasal cavity	4	AIDS-related	Surgery and radiotherapy	Positive	“Homosexual”, hepatitis B, syphilis/Complete resolution	3,476,707
28	M	37	Hard palate	NA	AIDS-related	Antiretroviral	Positive	Complete resolution	25,947,417
29	M	38	Soft palate, limbs, trunk, back, feet	NR	AIDS-related	Chemotherapy, antiretroviral	Positive	“Bisexual”/Complete resolution	38,444,698

NA: Information not available

The terms “homosexual” and “bisexual” are in quotes since they were used by the authors of those papers

Author Contributions

Clinical evaluation and follow-up was performed by IG, KA and AR. The manuscript was prepared by IG, SRS, RA, and IGK. The pathology evaluation was performed by SRS and IGK. All authors reviewed this manuscript.

Funding

No funding was necessary for this study.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Ethics Approval and Consent to Participate

For this type of study informed consent is not required. For this type of study consent for publication is not required. All procedures performed in studies involving the human participant were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The individual allowed photography of the lesions.

Consent for Publication

The clinical photographs used for the publication do not compromise the privacy of the individual.

Competing Interests

The authors declare no competing interests.

Conflict of Interest

The authors declare that they have no conflict of interest.

Code Availability

There is no software or custom code associated with this paper.