Nodular lesion on the posterior dorsal surface of the tongue

A 47-year-old man was referred to the Oral Medicine Service of our institution complaining of discomfort during eating and speaking because of the presence of a painless nodule on the posterior dorsal surface of the tongue. The patient had noticed the tongue lesion 1 month ago, and it had gradually expanded until it reached the size seen in the current clinical presentation. The medical history was noncontributory. Intraoral examination revealed a pink, pedunculated, exophytic, well-defined nodule, with a discretely lobulated and substantial ulcerated surface covered by a yellowish pseudomembrane without any tendency to bleed; measuring approximately 2 cm in greatest diameter; and located on the posterior dorsal region of the tongue (Figure 1). Considering that the clinical features of the nodule on the tongue favored a reactive lesion (pyogenic granuloma), benign tumor (schwannoma, neurofibroma, angioleiomyoma, rhabdomyoma, granular cell tumor, ectomesenchymal chondromyxoid tumor), and developmental abnormality (lingual thyroid), we did not include malignant neoplasms, such as squamous cell carcinoma (especially, the spindle cell variant), adenocarcinoma of minor salivary glands, soft tissue sarcoma and lymphoma in the differential diagnosis. The tongue is a common site for reactive lesions. Pyogenic granuloma is a common reactive lesion of the oral cavity and arises in a response to various stimuli, such chronic irritation or traumatic injury.1Jafarzadeh H. Sanatkhani M. Mohtasham N. Oral pyogenic granuloma: a review.J Oral Sci. 2006; 48: 167-175Crossref PubMed Scopus (242) Google Scholar This lesion can present with a wide variety of clinical appearances, ranging from a sessile lesion to an elevated mass.2Kamal R. Dahiya P. Puri A. Oral pyogenic granuloma: various concepts of etiopathogenesis.J Oral Maxillofac Pathol. 2012; 16: 79-82Crossref PubMed Scopus (92) Google Scholar Its development is slow, and it is asymptomatic, but it may also grow rapidly. The surface is characteristically ulcerated and may be covered by a yellowish-gray fibrinous membrane.1Jafarzadeh H. Sanatkhani M. Mohtasham N. Oral pyogenic granuloma: a review.J Oral Sci. 2006; 48: 167-175Crossref PubMed Scopus (242) Google Scholar The gingiva is the predominant site, followed by the lips, tongue, buccal mucosa, and hard palate.2Kamal R. Dahiya P. Puri A. Oral pyogenic granuloma: various concepts of etiopathogenesis.J Oral Maxillofac Pathol. 2012; 16: 79-82Crossref PubMed Scopus (92) Google Scholar,3Sharma S. Chandra S. Gupta S. Srivastava S. Heterogeneous conceptualization of etiopathogenesis: oral pyogenic granuloma.Natl J Maxillofac Surg. 2019; 10: 3-7Crossref PubMed Google Scholar Schwannomas, or neurilemmomas, are benign peripheral nerve tissue tumors that can be found in the oral cavity, preferentially on the tongue. Schwannomas may occur at any age and has no gender predilection. Clinically, it is an asymptomatic, slowly enlarging, nontender mass.4Rocha A.L. Nunes L.F.M. Travassos D.V. et al.A sessile nodule in the dorsum of the tongue.Oral Surg Oral Med Oral Pathol Oral Radiol. 2019; 128: 449-455Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Multiple schwannomas can be detected in patients with neurofibromatosis type 2 and schwannomatosis. Similar to schwannoma, neurofibroma can also manifest as an asymptomatic mass. Neurofibromas are often diagnosed in the second to fourth decades of life and have no gender predilection. However, patients with neurofibromatosis type 1 syndrome are diagnosed at younger ages, and not uncommonly, these tumors present as multiple neurofibromas. The tongue, buccal mucosa, gingiva, and lips can be affected by neurofibromas, with the tongue being the most common intraoral site.5Brito J.A. de Souza F.T. de Lacerda J.C. Bernardes V.F. Gomes C.C. Gomez R.S. Asymptomatic nodule in the tongue.Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 114: 281-283Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar,6Jouhilahti E.M. Visnapuu V. Soukka T. et al.Oral soft tissue alterations in patients with neurofibromatosis.Clin Oral Investig. 2012; 16: 551-558Crossref PubMed Scopus (28) Google Scholar Angioleiomyoma is a neoplastic proliferation of vascular smooth muscle cells and mainly affects middle-aged men, between the fourth and sixth decades of life. In the oral cavity, angioleiomyoma can affect the buccal mucosa, lips, tongue, palate, and gingiva. Clinically, it is a circumscribed, slow-growing, asymptomatic nodular lesion. Surgical excision is the treatment of choice. If completely removed, recurrence is rare.7Rawal S.Y. Rawal Y.B. Angioleiomyoma (vascular leiomyoma) of the oral cavity.Head Neck Pathol. 2018; 12: 123-126Crossref PubMed Scopus (12) Google Scholar Rhabdomyoma is a benign mesenchymal tumor of striated muscle origin, being topographically differentiated into cardiac and extracardiac types. Cardiac rhabdomyomas appear to be hamartomatous (often undergo spontaneous resolution) and show a strong association with tuberous sclerosis. Extracardiac rhabdomyomas comprise approximately 2% of the neoplasms with skeletal muscle differentiation. They can be divided into adult, fetal, and genital types. In the head and neck region, rhabdomyomas have been reported to affect the floor of the mouth, tongue, palate, lips, larynx, parapharynx, and submandibular spaces.8Karaman E. Saritzali G. Ozcora E. Rhabdomyoma of the tonsillar fossa.J Craniofac Surg. 2009; 20: 1207-1209Crossref PubMed Scopus (6) Google Scholar Granular cell tumor (GCT) is an uncommon benign neoplasm, believed to be neural in origin. Clinically, GCT is characterized by an asymptomatic solitary nodule, with a yellowish or normal-colored surface. About 45% to 65% of GCTs are located in the head and neck region; of these, 70% are located intraorally. The dorsum and the borders of the anterior two-thirds of the tongue, followed by buccal mucosa, are the most common sites affected in the oral cavity. There is female predilection (female-to-male ratio 2:1), with the mean age of occurrence being the fourth decade of life.9Van de Loo S. Thunnissen E. Postmus P. Van der Waal I. Granular cell tumor of the oral cavity: a case series including a case of metachronous occurrence in the tongue and the lung.Med Oral Patol Cir Bucal. 2015; 20: 30-33Crossref PubMed Scopus (19) Google Scholar,10Lafuente Ibáñez de Mendoza I. López Ortega K. Trierveiler M. et al.Oral granular cell tumour: a multicentric study of 56 cases and a systematic review.Oral Dis. 2020; 26: 573-589Crossref PubMed Scopus (2) Google Scholar Ectomesenchymal chondromyxoid tumor is a rare benign neoplasm of uncertain histogenesis, in most cases affecting the anterior dorsum of the tongue. In a few cases, the posterior dorsal tongue has been affected. This tumor mainly occurs between the third and sixth decades of life, clinically presenting as a slow-growing, painless nodule. There is no gender predilection. Surgical excision is the treatment of choice, and recurrence is rarely observed.11Almeida L.Y. Dominguete M.H.L. Dominguete P.R. Ribeiro-Silva A. Teixeira L.R. León J.E. Immune cell infiltration in ectomesenchymal chondromyxoid tumor: an immunohistochemical study.Oral Oncol. 2018; 81: 112-115Crossref PubMed Scopus (4) Google Scholar Lingual thyroid is a rare condition, defined as an ectopic thyroid gland tissue located in the midline of the tongue base and caused by a developmental anomaly of the descent of thyroid gland. It usually manifests as an asymptomatic nodular lesion. Interestingly, in autopsy studies, the prevalence is approximately 10%. In about 70% of the lingual thyroid cases, it is the only thyroid tissue present. Lingual thyroid is predominant in females (ratio varying from 4:1 to 7:1) and occurs often between ages 18 and 40 years, especially in the Asiatic population. Scintigraphy scanning with the use of Tc-99 m is the most useful diagnostic tool in localizing ectopic thyroid tissue.12Castro P.H. Volpato L.E. Tramujas J. Borges A.H. Ectopic thyroid at the base of the tongue of a young patient.Case Rep Dent. 2016; 20169174970PubMed Google Scholar Treatment of lingual thyroid consists of thyroid hormone therapy to suppress the lingual thyroid and reduce its size. Rarely, surgical excision is necessary, especially when ulceration or secondary infection is present.12Castro P.H. Volpato L.E. Tramujas J. Borges A.H. Ectopic thyroid at the base of the tongue of a young patient.Case Rep Dent. 2016; 20169174970PubMed Google Scholar On the basis of the possibilities of clinical diagnosis mentioned above, a reactive or benign lesion was favored, and an excisional biopsy was performed. Before this, scintigraphy examination was required to exclude the possibility of lingual thyroid, and the result was negative. Microscopy findings revealed fusocellular mesenchymal proliferation with fascicles of spindle-shaped cells, showing areas of vascular leakage and diffuse lymphoplasmacytic inflammatory infiltrate, red blood cell extravasation, siderophages, and eosinophilic globules. The proliferating cells exhibited hyperchromatism and scarce mitotic figures. At the periphery, focal ulcerated surface was evidenced (Figure 2). At the deepest part of the lesion, no infiltration into skeletal muscle tissue was detected. After histopathologic analysis, an immunohistochemical analysis, including the markers for CK AE1/AE3, epithelial membrane antigen, vimentin, alpha-smooth muscle actin, desmin, CD34, S100, p53, and Ki-67, was performed to characterize the spindle cell proliferation. The lesion revealed strong positivity for vimentin and CD34. The Ki-67 labeling index was 5%, whereas cells that were p53 positive were scarce. Complementary immunohistochemical analysis showed positivity for human herpesvirus‐8 (HHV‐8)–encoded latency‐associated nuclear antigen (Figure 3). Thus, the histopathologic and immunohistochemical findings were consistent with a diagnosis of Kaposi sarcoma (KS).Fig. 3Immunohistochemical analysis showed negativity for CK AE1/AE3 (A), whereas alpha-smooth muscle actin (SMA) (B) evidenced focal areas faintly positive. S100 (C) revealed only scarce dendritic-like cells through the entire tumor mass. Differently, CD34 was strongly positive (D). The Ki-67 labeling index was 5% (E). Notably, the human herpesvirus‐8 (HHV‐8)–encoded latency‐associated nuclear antigen was homogeneously positive (F) (A, × 10; B, × 40; C, × 10; D, × 10; E, × 10; F, × 10). A high-resolution version of these slides for use with the Virtual Microscope is available as eSlide: VM05823 (Figure 3D), VM05824 (Figure 3E), and VM05820 (Figure 3F).View Large Image Figure ViewerDownload Hi-res image Download (PPT) In view of this diagnosis, because KS is a condition that affects individuals with immunosuppressive states, serology for human immunodeficiency virus (HIV) was requested, and the result was positive. The patient was referred to specialized service for treatment and follow-up. Currently, he is well, without recurrence or alteration in the lesional area, and is under regular monitoring in our service (Figure 4). KS is a locally aggressive vascular neoplasm of intermediate-grade biologic potential and presents 4 clinical variants: classic, endemic, epidemic or acquired immunodeficiency syndrome (AIDS)–associated, and iatrogenic or post-transplantation types.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar KS is strongly associated with HHV-8 infection.14Sikora A.G. Shnayder Y. Yee H. DeLacure M.D. Oropharyngeal Kaposi sarcoma in related persons negative for human immunodeficiency virus.Ann Otol Rhinol Laryngol. 2008; 117: 172-176Crossref PubMed Scopus (8) Google Scholar In the head and neck region, KS is most often seen affecting the oral mucosa, specifically the hard and soft palates, the gingiva, and the tongue dorsum; however, some cases involving the mucosae of the pharynx, larynx, and nasal cavity have also been described. KS can present in the form of a solitary lesion or can affect multiple locations, with variations in size and shape, manifesting as a macule, which may progress to a papule, nodule, or exophytic mass.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar,15Keles E. Türker C. Artaş G. Karlıdağ T. Tonsillar Kaposi sarcoma in an HIV-negative patient: a case report.Turk Arch Otorhinolaryngol. 2019; 57: 46-49Crossref PubMed Google Scholar Microscopically, KS is characterized by a mixture of proliferating spindle-shaped cells, inflammatory cells, incomplete vascular slits, hyaline globules, and extravasated erythrocytes.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar The diagnosis of KS is supported by immunohistochemical analysis because positivity for endothelial markers (CD34, CD31, D2-40, Lyve-1, and factor VIII-related antigen), and mainly for HHV-8, confirms the final diagnosis.14Sikora A.G. Shnayder Y. Yee H. DeLacure M.D. Oropharyngeal Kaposi sarcoma in related persons negative for human immunodeficiency virus.Ann Otol Rhinol Laryngol. 2008; 117: 172-176Crossref PubMed Scopus (8) Google Scholar,16Lombardi N. Varoni E. Sardella A. Lodi G. Oral Kaposi's sarcoma in a HIV-negative young patient.Oral Oncol. 2020; 17104567Crossref Scopus (6) Google Scholar Moreover, the transcription factors erythroblast transformation-specific–related gene, Prox1, and Fli-1 are expressed in vascular endothelial cells and, therefore, are also potential markers for confirming the KS diagnosis.17Miettinen M. Wang Z.F. Paetau A. et al.ERG transcription factor as an immunohistochemical marker for vascular endothelial tumors and prostatic carcinoma.Am J Surg Pathol. 2011; 35: 432-441Crossref PubMed Scopus (227) Google Scholar In the current case, after KS diagnosis, a positive HIV test result was obtained. Of note, no other signs of HIV infection were observed. Instead, given the serologic result, the patient reported non-injected illicit drug use and unprotected extramarital sexual practices. As found in the current case, the epidemic and iatrogenic clinical variants of KS are the most frequent, in contrast to the endemic and classic variants of KS, which represent approximately 5% and 2% of the cases, respectively.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar In most cases of HIV-associated KS, the extraoral sites (skin, followed by visceral and lymphatic organs) are frequently involved. Simultaneous involvement of both skin and oral mucosa occurs between 16% and 25% of HIV-positive patients.18Birman E.G. Silveira F.R.X. Godoy L.F. Costa C.R. Kaposi's sarcoma in Brazilian AIDS patients: a study of 144 cases.Pesqui Odontol Bras. 2000; 14: 362-366Crossref Google Scholar,19Khammissa R.A. Pantanowitz L. Feller L. Oral HIV-associated Kaposi Sarcoma: a clinical study from the Ga-Rankuwa area, South Africa.AIDS Res Treat. 2012; 2012873171PubMed Google Scholar Oral KS occurs more often in men (age range 20– years). The hard palate, followed by the gingiva and the tongue, are the more affected sites.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar,18Birman E.G. Silveira F.R.X. Godoy L.F. Costa C.R. Kaposi's sarcoma in Brazilian AIDS patients: a study of 144 cases.Pesqui Odontol Bras. 2000; 14: 362-366Crossref Google Scholar,20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar A study assessing KS in Brazilian patients with AIDS showed that about 11% presented isolated oral KS.18Birman E.G. Silveira F.R.X. Godoy L.F. Costa C.R. Kaposi's sarcoma in Brazilian AIDS patients: a study of 144 cases.Pesqui Odontol Bras. 2000; 14: 362-366Crossref Google Scholar Additionally, it is relevant to mention that oral KS can be the initial clinical manifestation of HIV infection in 22% to 57% of patients,19Khammissa R.A. Pantanowitz L. Feller L. Oral HIV-associated Kaposi Sarcoma: a clinical study from the Ga-Rankuwa area, South Africa.AIDS Res Treat. 2012; 2012873171PubMed Google Scholar, 20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar, 21Fatahzadeh M. Kaposi sarcoma: review and medical management update.Oral Surg Oral Med Oral Pathol Oral Radiol. 2012; 113: 2-16Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar frequently affecting the palate,20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar,22Arul A.S. Kumar A.R. Verma S. Arul A.S. Oral Kaposi's sarcoma: sole presentation in HIV seropositive patient.J Nat Sci Biol Med. 2015; 6: 459-461Crossref PubMed Scopus (12) Google Scholar followed by the gingiva.20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar An interesting study showed that 12 (9%) of 134 patients with HIV-associated oral KS presented involvement of the tongue dorsum.20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar Relevantly, one of these cases (see Figure 4)20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar exhibited clinical characteristics, such as those described in the current case, and it was also the only evident lesion of KS.20Ficarra G. Berson A.M. Silverman Jr., S. et al.Kaposi's sarcoma of the oral cavity: a study of 134 patients with a review of the pathogenesis, epidemiology, clinical aspects, and treatment.Oral Surg Oral Med Oral Pathol. 1988; 66: 543-550Abstract Full Text PDF PubMed Scopus (101) Google Scholar Similarly, another study evaluating KS in Brazilian patients with AIDS observed that only 2 (1.4%) of 144 cases showed isolated tongue involvement.18Birman E.G. Silveira F.R.X. Godoy L.F. Costa C.R. Kaposi's sarcoma in Brazilian AIDS patients: a study of 144 cases.Pesqui Odontol Bras. 2000; 14: 362-366Crossref Google Scholar These findings show that isolated KS on the tongue is rare. To date, 12 cases of HIV-negative KS affecting the oral and oropharyngeal cavities have been reported in the literature (Table I). Notably, none of these patients had involvement of extraoral or extraoropharyngeal sites. Of them, 4 were females, and 8 were males (age range 28–83 years; mean 61 years). Clinically, these lesions presented as papules, nodules, and submucosal masses, affecting mainly the palate, palatine tonsil, and tongue and were clinically diagnosed as reactive lesions. Seven and five cases presented solitary and multiple lesions, respectively, and only 3 cases had unrelated systemic conditions, including type 2 diabetes mellitus, hypertension, and asthma. Interestingly, only 1 case was clinically diagnosed as lingual thyroid.23Bottler T. Kuttenberger J. Hardt N. Oehen H.P. Baltensperger M. Non-HIV-associated Kaposi's sarcoma of the tongue. Case report and review of the literature.Int J Oral Maxillofac Surg. 2007; 36: 1218-1220Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Therefore, when assessing nodular lesions on the midposterior dorsum of the tongue, lingual thyroid should be included in differential clinical diagnosis, especially if clinicopathologic features, such as age, gender, symptomatology, and time of evolution, are in accordance with this possibility, and it should be investigated by using scintigraphy, before the surgical treatment, because of the therapeutic and prognostic implications. Moreover, in cases that raise any suspicion, a detailed individual assessment supported by multidisciplinary team decision, is recommended. In HIV-negative patients, KS lesions were treated by surgery, chemotherapy, or radiotherapy, resulting in a good prognosis. In fact, none of these cases evidenced recurrence after treatment (see Table I). The presence of HHV-8 has been implicated in the pathogenesis of KS, frequently associated with a predisposing condition, such as immunosuppressive status. However, in the absence of this latter condition, it is difficult to explain the cellular and/or molecular mechanisms involved in the development of KS. In this context, it seems reasonable to think that most HIV-negative KS cases may be associated with age-associated immunologic dysfunction (immunosenescence) because 8 of 12 patients were aged between 53 and 86 years (see Table I).Table IClinicopathologic features of Kaposi sarcoma affecting HIV-negative patients in oral and oropharyngeal locationsCasesReferencesAge/GenderClinical presentationAnatomic locationClinical differential diagnosisHHV-8Systemic conditionsTreatment and prognosis1Reis-Filho et al., 200225Reis-Filho J.S. Souto-Moura C. Lopes J.M. Classic Kaposi's sarcoma of the tongue: case report with emphasis on the differential diagnosis.J Oral Maxillofac Surg. 2002; 60: 951-954Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar83/FBlue-to-purplish, nodular ulcerative lesionDorsal tonguePyogenic granuloma, angiomaNANASurgical excision; no recurrence2Kua et al., 200426Kua H.W. Merchant W. Waugh M.A. Oral Kaposi's sarcoma in a non-HIV homosexual white male.Int J STD AIDS. 2004; 15: 775-777Crossref PubMed Scopus (12) Google Scholar53/MVascular noduleBuccal mucosaNA+NAErythromycin stearate; no recurrence3Bottler et al., 200723Bottler T. Kuttenberger J. Hardt N. Oehen H.P. Baltensperger M. Non-HIV-associated Kaposi's sarcoma of the tongue. Case report and review of the literature.Int J Oral Maxillofac Surg. 2007; 36: 1218-1220Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar76/FExophytic nodular lesionDorsal tongueLingual thyroid+NALocal radiation; no recurrence4Mohanna et al., 200727Mohanna S. Bravo F. Ferrufino J.C. Sanchez J. Gotuzzo E. Classic Kaposi's sarcoma presenting in the oral cavity of two HIV-negative Quechua patients.Med Oral Patol Oral Cir Bucal. 2007; 12: E365-E368PubMed Google Scholar71/FMultiple red, painless papulesHard palateNA+NAChemotherapy; no recurrence56Sikora et al., 200814Sikora A.G. Shnayder Y. Yee H. DeLacure M.D. Oropharyngeal Kaposi sarcoma in related persons negative for human immunodeficiency virus.Ann Otol Rhinol Laryngol. 2008; 117: 172-176Crossref PubMed Scopus (8) Google Scholar49/M34/MSessile mass covered by pinkish mucosaWell-circumscribed massRight palatine tonsilLeft palatine tonsil extending to the left lateral oropharyngeal wallNA NA++NAAsthmaTonsillectomy; no recurrenceTonsillectomy; no recurrence7Ozbudak et al., 201124Ozbudak I.H. Guney K. Mutlu D. Gelen T. Ozbilim G. Bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient.Ear Nose Throat J. 2011; 90: E23-E26Crossref PubMed Scopus (6) Google Scholar68/MBilateral and asymmetric massesPalatine tonsilNA+NARadiotherapy and chemotherapy; no recurrence8Braga et al., 201228Braga D. Bezerra T. de Matos V. et al.Uncommon diagnosis of oral Kaposi's sarcoma in an elderly human immunodeficiency virus-seronegative adult.J Am Geriatr Soc. 2012; 60: 1174-1175Crossref PubMed Scopus (3) Google Scholar83/MPedunculated firm nodulesSoft palateNA+Arterial hypertensionNA9Faden et al., 201729Faden A. AlSheddi M. AlKindi M. Alabdulaaly L. Oral Kaposi sarcoma in HIV-seronegative Saudi patient: literature review and case report.Saudi Dent J. 2017; 29: 129-134Crossref PubMed Scopus (3) Google Scholar80/MMultiple dark red–purplish, painless lesionsHard palatePyogenic granuloma; granulomatous diseases+Type II diabetes mellitus and hypertensionRadiotherapy; no recurrence10Keles et al., 201915Keles E. Türker C. Artaş G. Karlıdağ T. Tonsillar Kaposi sarcoma in an HIV-negative patient: a case report.Turk Arch Otorhinolaryngol. 2019; 57: 46-49Crossref PubMed Google Scholar72/FA non-ulcerated, submucosal massRight palatine tonsilNA+NAChemotherapy; no recurrence11Sethia et al., 201930Sethia R. Hari-Raj A. Koenigs M. Ozer E. Non-HIV Oral Kaposi sarcoma: a case report and review of the literature.Ear Nose Throat J. 2019; 29145561319876917Google Scholar28/MMultiple nodular swelling lesionsUpper and lower gingiva and palateNA+NARadiotherapy; no recurrence12Lombardi et al., 202016Lombardi N. Varoni E. Sardella A. Lodi G. Oral Kaposi's sarcoma in a HIV-negative young patient.Oral Oncol. 2020; 17104567Crossref Scopus (6) Google Scholar35/MRounded, purplish, pedunculated massMucogingival junctionPyogenic granuloma; peripheral giant cell granuloma+NASurgical excision; no recurrenceWith regard to medications, only case 8 reported use of captopril.+, positive; F, female; HHV-8, human herpesvirus‐8; M, male; NA, not available. Open table in a new tab With regard to medications, only case 8 reported use of captopril. +, positive; F, female; HHV-8, human herpesvirus‐8; M, male; NA, not available. As previously mentioned, considering that AIDS-associated KS is one of the most frequent clinical presentations compared with other KS types, corresponding serologic tests should be performed in all KS cases to confirm or rule out such an association.24Ozbudak I.H. Guney K. Mutlu D. Gelen T. Ozbilim G. Bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient.Ear Nose Throat J. 2011; 90: E23-E26Crossref PubMed Scopus (6) Google Scholar The therapeutic approach for HIV-negative KS can be surgery, radiotherapy, chemotherapy, and interferon-α.14Sikora A.G. Shnayder Y. Yee H. DeLacure M.D. Oropharyngeal Kaposi sarcoma in related persons negative for human immunodeficiency virus.Ann Otol Rhinol Laryngol. 2008; 117: 172-176Crossref PubMed Scopus (8) Google Scholar, 15Keles E. Türker C. Artaş G. Karlıdağ T. Tonsillar Kaposi sarcoma in an HIV-negative patient: a case report.Turk Arch Otorhinolaryngol. 2019; 57: 46-49Crossref PubMed Google Scholar, 16Lombardi N. Varoni E. Sardella A. Lodi G. Oral Kaposi's sarcoma in a HIV-negative young patient.Oral Oncol. 2020; 17104567Crossref Scopus (6) Google Scholar,23Bottler T. Kuttenberger J. Hardt N. Oehen H.P. Baltensperger M. Non-HIV-associated Kaposi's sarcoma of the tongue. Case report and review of the literature.Int J Oral Maxillofac Surg. 2007; 36: 1218-1220Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 24Ozbudak I.H. Guney K. Mutlu D. Gelen T. Ozbilim G. Bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient.Ear Nose Throat J. 2011; 90: E23-E26Crossref PubMed Scopus (6) Google Scholar, 25Reis-Filho J.S. Souto-Moura C. Lopes J.M. Classic Kaposi's sarcoma of the tongue: case report with emphasis on the differential diagnosis.J Oral Maxillofac Surg. 2002; 60: 951-954Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 26Kua H.W. Merchant W. Waugh M.A. Oral Kaposi's sarcoma in a non-HIV homosexual white male.Int J STD AIDS. 2004; 15: 775-777Crossref PubMed Scopus (12) Google Scholar, 27Mohanna S. Bravo F. Ferrufino J.C. Sanchez J. Gotuzzo E. Classic Kaposi's sarcoma presenting in the oral cavity of two HIV-negative Quechua patients.Med Oral Patol Oral Cir Bucal. 2007; 12: E365-E368PubMed Google Scholar, 28Braga D. Bezerra T. de Matos V. et al.Uncommon diagnosis of oral Kaposi's sarcoma in an elderly human immunodeficiency virus-seronegative adult.J Am Geriatr Soc. 2012; 60: 1174-1175Crossref PubMed Scopus (3) Google Scholar, 29Faden A. AlSheddi M. AlKindi M. Alabdulaaly L. Oral Kaposi sarcoma in HIV-seronegative Saudi patient: literature review and case report.Saudi Dent J. 2017; 29: 129-134Crossref PubMed Scopus (3) Google Scholar, 30Sethia R. Hari-Raj A. Koenigs M. Ozer E. Non-HIV Oral Kaposi sarcoma: a case report and review of the literature.Ear Nose Throat J. 2019; 29145561319876917Google Scholar For KS associated with HIV, treatment with highly active antiretroviral therapy is the first modality considered. The prognosis is variable, depending on the KS type and the patient's immune status.13Fatahzadeh M. Schwartz R.A.. Oral Kaposi's sarcoma: a review and update.Int J Dermatol. 2013; 52: 666-672Crossref PubMed Scopus (37) Google Scholar,15Keles E. Türker C. Artaş G. Karlıdağ T. Tonsillar Kaposi sarcoma in an HIV-negative patient: a case report.Turk Arch Otorhinolaryngol. 2019; 57: 46-49Crossref PubMed Google Scholar The data reported in the literature reveal no KS recurrence after treatment in HIV-negative patients who do not have any other state of immunosuppression.14Sikora A.G. Shnayder Y. Yee H. DeLacure M.D. Oropharyngeal Kaposi sarcoma in related persons negative for human immunodeficiency virus.Ann Otol Rhinol Laryngol. 2008; 117: 172-176Crossref PubMed Scopus (8) Google Scholar, 15Keles E. Türker C. Artaş G. Karlıdağ T. Tonsillar Kaposi sarcoma in an HIV-negative patient: a case report.Turk Arch Otorhinolaryngol. 2019; 57: 46-49Crossref PubMed Google Scholar, 16Lombardi N. Varoni E. Sardella A. Lodi G. 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Non-HIV Oral Kaposi sarcoma: a case report and review of the literature.Ear Nose Throat J. 2019; 29145561319876917Google Scholar In summary, KS should be included in the differential diagnosis when assessing nodular lesions on the dorsal surface of the tongue, regardless of HIV status. For these lesions, surgical excision is the treatment of choice, usually yielding a good prognosis. Importantly, immunohistochemical analysis for HHV-8 is crucial for confirming the diagnosis, because it has a significant impact on its treatment and prognosis.