- Email: [email protected]
Asymptomatic gingival lesion occurring in an 83-year-old man
Vol.
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No.
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Month 2013
Asymptomatic gingival lesion occurring in an 83-year-old man Andrew Rockafellow,a Eugene Ko, DDS,b and Elizabeth Philipone, DMDc Columbia University College of Dental Medicine, New York, NY, USA
(Oral Surg Oral Med Oral Pathol Oral Radiol 2013;-:1-4)
CLINICAL PRESENTATION An 83-year-old man presented to his periodontist for routine periodontal maintenance, at which time a dusky-red, smooth-surfaced, 4 3-mm nodule was noted at the junction of the attached and unattached gingivae of the right anterior maxilla. Although the patient could not recall when the lesion first occurred, the lesion was not present at the patient’s office visit 6 months earlier. Close examination also found a faint bluish elevation of the mucosa superior and posterior to the apparent nodule (Figure 1). The right maxillary central and lateral incisors had both been extracted several years prior, and a fixed bridge was in place, with the right canine serving as one of the abutments. Periapical radiographic examination of the site was unremarkable. The right maxillary canine had been successfully endodontically treated and had unremarkable pocket depths. The lesion was asymptomatic. The clinician was not able to appreciate any significant blanching when pressure was applied to the lesion. A review of the patient’s medical history found benign prostatic hyperplasia, dyspepsia, hypercholesterolemia, hypertension, and seasonal allergies. The patient had also been diagnosed with classic Kaposi sarcoma (CKS) over a decade earlier. He currently presented with multiple cutaneous lesions of his lower right and left legs. The lesions had recently experienced an exacerbation, becoming more numerous and larger. His prescription medications included colesevelam, hydrochlorothiazide, losartan, omeprazole, terazosin, and valsartan. He presently was receiving infusions of doxorubicin to treat his multiple cutaneous CKS leg lesions and to alleviate the symptomatic edema he was experiencing in his lower extremities. The patient had recently begun his first cycle of doxorubicin. Doxorubicin is a chemotherapeutic agent used in the treatment of many different malignancies, including Kaposi sarcoma (KS). Doxorubicin is administered intravenously a Student Researcher, Columbia University College of Dental Medicine. b Oral Pathology Resident, Columbia University College of Dental Medicine. c Assistant Professor and Assistant Attending Physician in Oral & Maxillofacial Pathology, Columbia University College of Dental Medicine. Received for publication Jun 27, 2013; returned for revision Oct 20, 2013; accepted for publication Oct 29, 2013. Ó 2013 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.10.015
and results in inhibition of DNA and RNA synthesis. Doxorubicin can cause marrow suppression, and therefore a balance between its immunosuppressive effect and its antineoplastic benefit must be achieved. According to the patient, his cutaneous lesions showed an initial response to the administration of doxorubicin. However, recurrences did occur, requiring additional infusions.
DIFFERENTIAL DIAGNOSIS The clinical features of an asymptomatic, smoothsurfaced, dusky-red gingival nodule led us to favor a benign vascular or giant cell lesion. A diagnosis of a peripheral giant cell granuloma was then considered, because they are relatively common tumor-like growths. They are characteristically described as being dusky-red, are by definition located on the gingiva or alveolar ridge, and can occur at any age, most frequently during the first to sixth decades.1 Although peripheral giant cell granulomas occur slightly more frequently in the mandible and in females,1 our patient’s age and gender would not preclude diagnosis of peripheral giant cell granuloma. In addition, the lack of blanching would support a diagnosis of peripheral giant cell granuloma. Pyogenic granuloma was then examined as a potential diagnosis. Of all the entities considered in the differential diagnostic list, pyogenic granuloma is the most common. Compared with peripheral giant cell granulomas, pyogenic granulomas are typically redder and less dusky in color. Although this lesion appeared dusky-red to us, the color does not negate a pyogenic granuloma as a diagnostic possibility. Although the natural teeth were no longer present at the site, local irritation or inflammation could have occurred and precipitated the development of a pyogenic granuloma. Even though pyogenic granulomas are more common in younger patients, they can occur at any age. The lack of bleeding upon gentle manipulation of this lesion was not typical of pyogenic granulomas, which tend to be friable and to bleed easily. Hemangioma and a vascular malformation were both briefly considered. However, hemangiomas typically arise during the first 8 weeks of life, and vascular malformations are present at birth. Whereas vascular malformations persist throughout life, most hemangiomas will gradually involute.1 The fact that our patient’s lesion presented within the previous 6 months virtually eliminates these 2 entities as diagnostic possibilities. 1
CLINICOPATHOLOGIC CONFERENCE 2 Rockafellow, Ko and Philipone
OOOO Month 2013
allowed to heal by secondary intention. Histopathologic examination of the specimen found a proliferation of plump, spindle-shaped cells forming numerous slit-like vascular channels (Figure 2, A, B). The spindle cells were positive for CD31, confirming endothelial origin. In situ hybridization was performed for human herpesvirus 8 (HHV-8) latency-associated nuclear antigen 1 (LANA-1); this test was positive (Figure 3). Therefore, a diagnosis of Kaposi sarcoma was rendered.
Fig. 1. Clinical intraoral photograph depicting a 4 3-mm dusky-red gingival nodule. A faint, slightly elevated bluish appearance of the adjacent mucosal is also appreciated. An incidental finding of a small mucosal tag apical to the maxillary right central incisor was also noted.
Although the patient did not recall any trauma to the area, a traumatic angiomatous lesion was considered. Also referred to as a venous pool, venous lake, or venous aneurysm, a traumatic angiomatous lesion is the result of acute trauma to a subepithelial vein, resulting in a persistent focus of dilation. Clinically, it appears as a reddish-blue, sessile, subepithelial nodule that will blanch unless thrombosed. It is most common in older adults and has a predilection for the lower lip and buccal mucosa.2 The possibility of this lesion representing a malignant vascular tumor was considered unlikely because of the painless and well-defined clinical presentation, as well as the lack of osseous involvement. The only malignant lesion that was entertained was KS. KS was considered because of the patient’s history of CKS. Although rare, CKS lesions of the oral cavity can occur. Tufted angioma, a benign lesion, was then considered as another possible diagnosis. Although tufted angiomas are rare in the oral cavity, clinical presentation as an asymptomatic purple-red papule of the oral mucosa has been described.3 It occurs more frequently in children, but adult onset can occur. Microscopically, tufted angioma is composed of collections of closely set capillary-sized vessels, often occurring in a lobular pattern. It is believed to be closely related to the form of pyogenic granuloma designated lobular capillary hemangioma.4 In summary, our case involved an 83-year-old man with a painless, dusky-red, soft tissue, nonblanching nodule located at the junction of the attached and unattached facial gingivae of the right maxilla. Our favored clinical diagnosis was peripheral giant cell granuloma.
DIAGNOSIS After informed consent was obtained, local anesthesia was administered, and the lesion was excised and submitted for histologic examination. The site was then
MANAGEMENT The medical oncologist treating the patient’s CKS cutaneous leg lesions was informed of the diagnosis. The patient continues to receive infusions of doxorubicin. At 6-month postoperative follow-up, neither recurrence nor new oral lesions were noted. DISCUSSION KS is an angioproliferative disease induced by HHV-8 infection. The condition was first described by Moritz Kaposi in 1872.5 However, association with HHV-8 was not recognized until 1994.6 Although HHV-8 infection is the primary factor in the development of KS, researchers have suggested that the disease is multifactorial, involving not only HHV-8 infection, but also cytokine-induced growth together with an immunocompromised status.7 Four subtypes have been recognized: Classic KS (CKS), African endemic KS; KS in iatrogenically immunosuppressed patients; and AIDS-related KS. CKS most often affects older men of Mediterranean or Central/Eastern European descent.8 It is most frequently a chronic, indolent disease that rarely affects patient survival. Although infection with HHV-8 is necessary, only a small percentage of those infected go on to develop CKS.9 Thus, researchers have attempted to identify cofactors that would predispose an individual to develop CKS. Among the reported risk factors are high HHV-8 antibody titers, high viral load, genetic variations affecting cytokine production,10 and immunosuppression.11,12 CKS is not associated with human immunodeficiency virus (HIV) infection.8 Because doxorubicin can cause marrow suppression, we speculate that our patient’s iatrogenic immunosuppression from his doxorubicin infusions, in conjunction with his advanced age, contributed to the development of his oral lesion. To the best of our knowledge, the oral lesion was an isolated finding, because the patient’s dermal lesions, although impressive, were restricted to his legs, and he lacked any visceral involvement. The lesions of CKS are predominantly cutaneous, typically presenting as purple/reddish-blue, or dark brown/black macules, plaques, or nodules. The skin of the distal extremities is the most often affected site, with lesions ranging in size from a few millimeters to several
OOOO Volume -, Number
CLINICOPATHOLOGIC CONFERENCE Rockafellow, Ko and Philipone 3
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Fig. 2. Photomicrographs (hematoxylin-eosin, original magnification 40 [A] and original magnification 400 [B]) showing a mucosal proliferation of plump, spindle-shaped cells forming numerous, elongated vascular channels.
Fig. 3. Latency-associated nuclear antigen 1 immunohistochemically stained photomicrograph (original magnification 200), highlighting the presence of latent human herpesvirus 8 within the lesional cells.
used to detect the presence of HHV-8 within the spindle cells, thus confirming the diagnosis. Treatment of KS is based on the subtype and whether lesions are localized or disseminated. Localized cutaneous disease can be treated with cryotherapy,23,24 laser therapy,25,26 electrochemotherapy,27 topical immunotherapy,28 intralesional injections of chemotherapeutic agents,27,29 radiation, or surgical excision. Advanced or disseminated disease could require intravenous chemoand immunotherapy.30 These treatment modalities do not eliminate the HHV-8 virus but can decrease the size of the lesions and delay or prevent progression. The patient in our case was treated by his oncologist with infusions of doxorubicin for his multiple cutaneous leg lesions. Since excisional biopsy, his oral lesion has not recurred. This case was courtesy of Robert Jaffin, DMD, Hackensack, NJ, USA.
REFERENCES 8
centimeters in diameter. Extracutaneous lesions have been reported to affect less than 10% of CKS patients.12-14 Oral KS lesions in patients with CKS have been reported but are rare. There have been isolated case reports and several retrospective reviews published.12-19 When oral lesions do occur, the most common sites of presentation have been found to be the palate (hard and soft) followed by the oropharynx.20 Within the oral cavity, KS can present as either flat or nodular growths that range in color from reddish to brown or purple, with a predilection for the palatal mucosa and oropharyngeal region.21 Microscopically, KS is characterized by a proliferation of spindle-shaped endothelial cells and atypical, often slit-like vascular channels. Extravasated red blood cells and hemosiderin deposition are also often observed.22 Today, immunohistochemical staining with HHV-8 LANA-1 can be
1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd ed. St Louis, MO: Saunders; 2009. 2. Gnepp DR. Diagnostic Surgical Pathology of the Head and Neck. 2nd ed. Philadelphia, PA: Saunders; 2009. 3. Kleinegger CL, Hammond HL, Vincent SD, Finkelstein MW. Acquired tufted angioma: a unique vascular lesion not previously reported in the oral mucosa. Br J Dermatol. 2000;142:794-799. 4. Padilla RS, Orkin M, Rosai J. Acquired “tufted” angioma (progressive capillary hemangioma): a distinctive clinicopathologic entity related to lobular capillary hemangioma. Am J Dermatopathol. 1987;9:292-300. 5. Kaposi M. Idiopathic multiple pigmented sarcoma of the skin. [English translation from Archiv für Dermatologie und Syphilis 1872;4:265-273]. CA Cancer J Clin. 1982;32:342. 6. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865-1869. 7. Hengge UR, Ruzicka T, Tyring SK, et al. Update on Kaposi’s sarcoma and other HHV8 associated diseases, part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy. Lancet. 2002;2:281-292.
CLINICOPATHOLOGIC CONFERENCE 4 Rockafellow, Ko and Philipone 8. Rothman S. Remarks on sex, age and racial distribution of Kaposi’s sarcoma and on possible pathogenetic factors. Acta Un Int Cancer. 1962;18:326-329. 9. Vitale F, Briffa DV, Whitby D, et al. Kaposi’s sarcoma herpesvirus and Kaposi’s sarcoma in the elderly populations of 3 Mediterranean islands. Int J Cancer. 2001;91:588. 10. Brown EE, Whitby D, Vitale F, et al. Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer. 2006;107:2282. 11. Mancuso R, Biffi R, Valli M, et al. HHV8: a subtype is associated with rapidly evolving classic Kaposi’s sarcoma. J Med Virol. 2008;80:2153. 12. Stratigos JD, Potouridou I, Katoulis AC, et al. Classic Kaposi’s sarcoma in Greece: a clinico-epidemiological profile. Int J Dermatol. 1997;36:735C. 13. Jaimovich L, Calb I, Kaminsky A. Kaposi’s sarcoma of the conjunctiva. J Am Acad Dermatol. 1986;14:589. 14. Cottoni F, Masala MV, Piras P, Montesu MA, Cerimele D. Mucosal involvement in classic Kaposi’s sarcoma. Br J Dermatol. 2003;148:1273. 15. Mohanna S, Bravo F, Ferrufino JC, Sanchez J, Gotuzzo E. Classic Kaposi’s sarcoma presenting in the oral cavity of two HIVnegative Quechua patients. Med Oral Patol Oral Cir Bucal. 2007;12:E365-E368. 16. Dal Maso L, Polesel J, Ascoli V, et al. Classic Kaposi’s sarcoma in Italy, 1985-1998. Br J Cancer. 2005;92:188-193. 17. Dilnur P, Katano H, Wang ZH, et al. Classic type of Kaposi’s sarcoma and human herpesvirus 8 infection in Xinjiang, China. Pathol Int. 2001;51:845-852. 18. Garcia A, Olivella F, Valderrama S, Rodríguez G. Kaposi’s sarcoma in Colombia. Cancer. 1989;64:2393-2398. 19. Jindal JR, Campbell BH, Ward TO, Almagro US. Kaposi’s sarcoma of the oral cavity in a non-AIDS patient: case report and review of the literature. Head Neck. 1995;17:64-68. 20. Patrikidou A, Vahtsevanos K, Charalambidou M, Valeri RM, Xirou P, Antoniades K. Non-AIDS Kaposi’s sarcoma in the head and neck area. Head Neck. 2009;31:260-268. 21. Lozada F, Silverman S Jr, Migliorati CA, Conant MA, Volberding PA. Oral manifestations of tumor and opportunistic
OOOO Month 2013
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23. 24.
25.
26.
27.
28.
29. 30.
infections in the acquired immunodeficiency syndrome (AIDS): findings in 53 homosexual males with Kaposi’s sarcoma. Oral Surg. 1983;56:491-494. Green TL, Beckstead JH, Lozada-Nur F, Silverman S, Hansen LS. Histopathologic spectrum of oral Kaposi’s sarcoma. Oral Surg Oral Med Oral Pathol. 1984;58:306-314. Von Roenn JH, Cianfrocca M. Treatment of Kaposi’s sarcoma. Cancer Treat Res. 2001;104:127. Webster GF. Local therapy for mucocutaneous Kaposi’s sarcoma in patients with acquired immunodeficiency syndrome. Dermatol Surg. 1995;21:205. Chun YS, Chang SN, Park WH. A case of classical Kaposi’s sarcoma of the penis showing a good response to high-energy pulsed carbon dioxide laser therapy. J Dermatol. 1999;26:240. Marchell N, Alster TS. Successful treatment of cutaneous Kaposi’s sarcoma by the 585-nm pulsed dye laser. Dermatol Surg. 1997;23:973. Brambilla L, Bellinvia M, Tourlaki A, Scoppio B, Gaiani F, Boneschi V. Intralesional vincristine as first-line therapy for nodular lesions in classic Kaposi sarcoma: a prospective study in 151 patients. Br J Dermatol. 2010;162:854. Goiriz R, Ríos-Buceta L, De Arriba AG, Aragüés M, GarcíaDiez A. Treatment of classic Kaposi’s sarcoma with topical imiquimod. Dermatol Surg. 2009;35:147. Odom RB, Goette DK. Treatment of cutaneous Kaposi’s sarcoma with intralesional vincristine. Arch Dermatol. 1978;114:1693. Active protocols for treatment of Kaposi’s sarcoma. Available at: www.cancer.gov/clinicaltrials/search. Accessed February 29, 2012.
Reprint requests: Andrew Rockafellow Columbia University College of Dental Medicine Mailbox 24G 100 Haven Ave New York, NY 10032 USA [email protected]
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No.
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Month 2013
Asymptomatic gingival lesion occurring in an 83-year-old man Andrew Rockafellow,a Eugene Ko, DDS,b and Elizabeth Philipone, DMDc Columbia University College of Dental Medicine, New York, NY, USA
(Oral Surg Oral Med Oral Pathol Oral Radiol 2013;-:1-4)
CLINICAL PRESENTATION An 83-year-old man presented to his periodontist for routine periodontal maintenance, at which time a dusky-red, smooth-surfaced, 4 3-mm nodule was noted at the junction of the attached and unattached gingivae of the right anterior maxilla. Although the patient could not recall when the lesion first occurred, the lesion was not present at the patient’s office visit 6 months earlier. Close examination also found a faint bluish elevation of the mucosa superior and posterior to the apparent nodule (Figure 1). The right maxillary central and lateral incisors had both been extracted several years prior, and a fixed bridge was in place, with the right canine serving as one of the abutments. Periapical radiographic examination of the site was unremarkable. The right maxillary canine had been successfully endodontically treated and had unremarkable pocket depths. The lesion was asymptomatic. The clinician was not able to appreciate any significant blanching when pressure was applied to the lesion. A review of the patient’s medical history found benign prostatic hyperplasia, dyspepsia, hypercholesterolemia, hypertension, and seasonal allergies. The patient had also been diagnosed with classic Kaposi sarcoma (CKS) over a decade earlier. He currently presented with multiple cutaneous lesions of his lower right and left legs. The lesions had recently experienced an exacerbation, becoming more numerous and larger. His prescription medications included colesevelam, hydrochlorothiazide, losartan, omeprazole, terazosin, and valsartan. He presently was receiving infusions of doxorubicin to treat his multiple cutaneous CKS leg lesions and to alleviate the symptomatic edema he was experiencing in his lower extremities. The patient had recently begun his first cycle of doxorubicin. Doxorubicin is a chemotherapeutic agent used in the treatment of many different malignancies, including Kaposi sarcoma (KS). Doxorubicin is administered intravenously a Student Researcher, Columbia University College of Dental Medicine. b Oral Pathology Resident, Columbia University College of Dental Medicine. c Assistant Professor and Assistant Attending Physician in Oral & Maxillofacial Pathology, Columbia University College of Dental Medicine. Received for publication Jun 27, 2013; returned for revision Oct 20, 2013; accepted for publication Oct 29, 2013. Ó 2013 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2013.10.015
and results in inhibition of DNA and RNA synthesis. Doxorubicin can cause marrow suppression, and therefore a balance between its immunosuppressive effect and its antineoplastic benefit must be achieved. According to the patient, his cutaneous lesions showed an initial response to the administration of doxorubicin. However, recurrences did occur, requiring additional infusions.
DIFFERENTIAL DIAGNOSIS The clinical features of an asymptomatic, smoothsurfaced, dusky-red gingival nodule led us to favor a benign vascular or giant cell lesion. A diagnosis of a peripheral giant cell granuloma was then considered, because they are relatively common tumor-like growths. They are characteristically described as being dusky-red, are by definition located on the gingiva or alveolar ridge, and can occur at any age, most frequently during the first to sixth decades.1 Although peripheral giant cell granulomas occur slightly more frequently in the mandible and in females,1 our patient’s age and gender would not preclude diagnosis of peripheral giant cell granuloma. In addition, the lack of blanching would support a diagnosis of peripheral giant cell granuloma. Pyogenic granuloma was then examined as a potential diagnosis. Of all the entities considered in the differential diagnostic list, pyogenic granuloma is the most common. Compared with peripheral giant cell granulomas, pyogenic granulomas are typically redder and less dusky in color. Although this lesion appeared dusky-red to us, the color does not negate a pyogenic granuloma as a diagnostic possibility. Although the natural teeth were no longer present at the site, local irritation or inflammation could have occurred and precipitated the development of a pyogenic granuloma. Even though pyogenic granulomas are more common in younger patients, they can occur at any age. The lack of bleeding upon gentle manipulation of this lesion was not typical of pyogenic granulomas, which tend to be friable and to bleed easily. Hemangioma and a vascular malformation were both briefly considered. However, hemangiomas typically arise during the first 8 weeks of life, and vascular malformations are present at birth. Whereas vascular malformations persist throughout life, most hemangiomas will gradually involute.1 The fact that our patient’s lesion presented within the previous 6 months virtually eliminates these 2 entities as diagnostic possibilities. 1
CLINICOPATHOLOGIC CONFERENCE 2 Rockafellow, Ko and Philipone
OOOO Month 2013
allowed to heal by secondary intention. Histopathologic examination of the specimen found a proliferation of plump, spindle-shaped cells forming numerous slit-like vascular channels (Figure 2, A, B). The spindle cells were positive for CD31, confirming endothelial origin. In situ hybridization was performed for human herpesvirus 8 (HHV-8) latency-associated nuclear antigen 1 (LANA-1); this test was positive (Figure 3). Therefore, a diagnosis of Kaposi sarcoma was rendered.
Fig. 1. Clinical intraoral photograph depicting a 4 3-mm dusky-red gingival nodule. A faint, slightly elevated bluish appearance of the adjacent mucosal is also appreciated. An incidental finding of a small mucosal tag apical to the maxillary right central incisor was also noted.
Although the patient did not recall any trauma to the area, a traumatic angiomatous lesion was considered. Also referred to as a venous pool, venous lake, or venous aneurysm, a traumatic angiomatous lesion is the result of acute trauma to a subepithelial vein, resulting in a persistent focus of dilation. Clinically, it appears as a reddish-blue, sessile, subepithelial nodule that will blanch unless thrombosed. It is most common in older adults and has a predilection for the lower lip and buccal mucosa.2 The possibility of this lesion representing a malignant vascular tumor was considered unlikely because of the painless and well-defined clinical presentation, as well as the lack of osseous involvement. The only malignant lesion that was entertained was KS. KS was considered because of the patient’s history of CKS. Although rare, CKS lesions of the oral cavity can occur. Tufted angioma, a benign lesion, was then considered as another possible diagnosis. Although tufted angiomas are rare in the oral cavity, clinical presentation as an asymptomatic purple-red papule of the oral mucosa has been described.3 It occurs more frequently in children, but adult onset can occur. Microscopically, tufted angioma is composed of collections of closely set capillary-sized vessels, often occurring in a lobular pattern. It is believed to be closely related to the form of pyogenic granuloma designated lobular capillary hemangioma.4 In summary, our case involved an 83-year-old man with a painless, dusky-red, soft tissue, nonblanching nodule located at the junction of the attached and unattached facial gingivae of the right maxilla. Our favored clinical diagnosis was peripheral giant cell granuloma.
DIAGNOSIS After informed consent was obtained, local anesthesia was administered, and the lesion was excised and submitted for histologic examination. The site was then
MANAGEMENT The medical oncologist treating the patient’s CKS cutaneous leg lesions was informed of the diagnosis. The patient continues to receive infusions of doxorubicin. At 6-month postoperative follow-up, neither recurrence nor new oral lesions were noted. DISCUSSION KS is an angioproliferative disease induced by HHV-8 infection. The condition was first described by Moritz Kaposi in 1872.5 However, association with HHV-8 was not recognized until 1994.6 Although HHV-8 infection is the primary factor in the development of KS, researchers have suggested that the disease is multifactorial, involving not only HHV-8 infection, but also cytokine-induced growth together with an immunocompromised status.7 Four subtypes have been recognized: Classic KS (CKS), African endemic KS; KS in iatrogenically immunosuppressed patients; and AIDS-related KS. CKS most often affects older men of Mediterranean or Central/Eastern European descent.8 It is most frequently a chronic, indolent disease that rarely affects patient survival. Although infection with HHV-8 is necessary, only a small percentage of those infected go on to develop CKS.9 Thus, researchers have attempted to identify cofactors that would predispose an individual to develop CKS. Among the reported risk factors are high HHV-8 antibody titers, high viral load, genetic variations affecting cytokine production,10 and immunosuppression.11,12 CKS is not associated with human immunodeficiency virus (HIV) infection.8 Because doxorubicin can cause marrow suppression, we speculate that our patient’s iatrogenic immunosuppression from his doxorubicin infusions, in conjunction with his advanced age, contributed to the development of his oral lesion. To the best of our knowledge, the oral lesion was an isolated finding, because the patient’s dermal lesions, although impressive, were restricted to his legs, and he lacked any visceral involvement. The lesions of CKS are predominantly cutaneous, typically presenting as purple/reddish-blue, or dark brown/black macules, plaques, or nodules. The skin of the distal extremities is the most often affected site, with lesions ranging in size from a few millimeters to several
OOOO Volume -, Number
CLINICOPATHOLOGIC CONFERENCE Rockafellow, Ko and Philipone 3
-
Fig. 2. Photomicrographs (hematoxylin-eosin, original magnification 40 [A] and original magnification 400 [B]) showing a mucosal proliferation of plump, spindle-shaped cells forming numerous, elongated vascular channels.
Fig. 3. Latency-associated nuclear antigen 1 immunohistochemically stained photomicrograph (original magnification 200), highlighting the presence of latent human herpesvirus 8 within the lesional cells.
used to detect the presence of HHV-8 within the spindle cells, thus confirming the diagnosis. Treatment of KS is based on the subtype and whether lesions are localized or disseminated. Localized cutaneous disease can be treated with cryotherapy,23,24 laser therapy,25,26 electrochemotherapy,27 topical immunotherapy,28 intralesional injections of chemotherapeutic agents,27,29 radiation, or surgical excision. Advanced or disseminated disease could require intravenous chemoand immunotherapy.30 These treatment modalities do not eliminate the HHV-8 virus but can decrease the size of the lesions and delay or prevent progression. The patient in our case was treated by his oncologist with infusions of doxorubicin for his multiple cutaneous leg lesions. Since excisional biopsy, his oral lesion has not recurred. This case was courtesy of Robert Jaffin, DMD, Hackensack, NJ, USA.
REFERENCES 8
centimeters in diameter. Extracutaneous lesions have been reported to affect less than 10% of CKS patients.12-14 Oral KS lesions in patients with CKS have been reported but are rare. There have been isolated case reports and several retrospective reviews published.12-19 When oral lesions do occur, the most common sites of presentation have been found to be the palate (hard and soft) followed by the oropharynx.20 Within the oral cavity, KS can present as either flat or nodular growths that range in color from reddish to brown or purple, with a predilection for the palatal mucosa and oropharyngeal region.21 Microscopically, KS is characterized by a proliferation of spindle-shaped endothelial cells and atypical, often slit-like vascular channels. Extravasated red blood cells and hemosiderin deposition are also often observed.22 Today, immunohistochemical staining with HHV-8 LANA-1 can be
1. Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and Maxillofacial Pathology. 3rd ed. St Louis, MO: Saunders; 2009. 2. Gnepp DR. Diagnostic Surgical Pathology of the Head and Neck. 2nd ed. Philadelphia, PA: Saunders; 2009. 3. Kleinegger CL, Hammond HL, Vincent SD, Finkelstein MW. Acquired tufted angioma: a unique vascular lesion not previously reported in the oral mucosa. Br J Dermatol. 2000;142:794-799. 4. Padilla RS, Orkin M, Rosai J. Acquired “tufted” angioma (progressive capillary hemangioma): a distinctive clinicopathologic entity related to lobular capillary hemangioma. Am J Dermatopathol. 1987;9:292-300. 5. Kaposi M. Idiopathic multiple pigmented sarcoma of the skin. [English translation from Archiv für Dermatologie und Syphilis 1872;4:265-273]. CA Cancer J Clin. 1982;32:342. 6. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266:1865-1869. 7. Hengge UR, Ruzicka T, Tyring SK, et al. Update on Kaposi’s sarcoma and other HHV8 associated diseases, part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy. Lancet. 2002;2:281-292.
CLINICOPATHOLOGIC CONFERENCE 4 Rockafellow, Ko and Philipone 8. Rothman S. Remarks on sex, age and racial distribution of Kaposi’s sarcoma and on possible pathogenetic factors. Acta Un Int Cancer. 1962;18:326-329. 9. Vitale F, Briffa DV, Whitby D, et al. Kaposi’s sarcoma herpesvirus and Kaposi’s sarcoma in the elderly populations of 3 Mediterranean islands. Int J Cancer. 2001;91:588. 10. Brown EE, Whitby D, Vitale F, et al. Virologic, hematologic, and immunologic risk factors for classic Kaposi sarcoma. Cancer. 2006;107:2282. 11. Mancuso R, Biffi R, Valli M, et al. HHV8: a subtype is associated with rapidly evolving classic Kaposi’s sarcoma. J Med Virol. 2008;80:2153. 12. Stratigos JD, Potouridou I, Katoulis AC, et al. Classic Kaposi’s sarcoma in Greece: a clinico-epidemiological profile. Int J Dermatol. 1997;36:735C. 13. Jaimovich L, Calb I, Kaminsky A. Kaposi’s sarcoma of the conjunctiva. J Am Acad Dermatol. 1986;14:589. 14. Cottoni F, Masala MV, Piras P, Montesu MA, Cerimele D. Mucosal involvement in classic Kaposi’s sarcoma. Br J Dermatol. 2003;148:1273. 15. Mohanna S, Bravo F, Ferrufino JC, Sanchez J, Gotuzzo E. Classic Kaposi’s sarcoma presenting in the oral cavity of two HIVnegative Quechua patients. Med Oral Patol Oral Cir Bucal. 2007;12:E365-E368. 16. Dal Maso L, Polesel J, Ascoli V, et al. Classic Kaposi’s sarcoma in Italy, 1985-1998. Br J Cancer. 2005;92:188-193. 17. Dilnur P, Katano H, Wang ZH, et al. Classic type of Kaposi’s sarcoma and human herpesvirus 8 infection in Xinjiang, China. Pathol Int. 2001;51:845-852. 18. Garcia A, Olivella F, Valderrama S, Rodríguez G. Kaposi’s sarcoma in Colombia. Cancer. 1989;64:2393-2398. 19. Jindal JR, Campbell BH, Ward TO, Almagro US. Kaposi’s sarcoma of the oral cavity in a non-AIDS patient: case report and review of the literature. Head Neck. 1995;17:64-68. 20. Patrikidou A, Vahtsevanos K, Charalambidou M, Valeri RM, Xirou P, Antoniades K. Non-AIDS Kaposi’s sarcoma in the head and neck area. Head Neck. 2009;31:260-268. 21. Lozada F, Silverman S Jr, Migliorati CA, Conant MA, Volberding PA. Oral manifestations of tumor and opportunistic
OOOO Month 2013
22.
23. 24.
25.
26.
27.
28.
29. 30.
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