Squamous cell carcinoma of the tongue complicating chronic oral mucosal graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation

Abstract

Two patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia. Chronic graft-versus-host disease (GVHD) developed, with persistent symptomatic oral lesions. At 2 and 6 years post-HSCT, both patients developed squamous cell carcinoma (SCC) of the tongue in areas previously involved by chronic GVHD. None had any known risk factor for SCC. Histologically, moderate to severe dysplasia was present in noncancerous oral mucosa. Oral SCC is rarely described after HSCT, and a review of the reported cases showed chronic GVHD to be a common risk, suggesting that the chronic inflammation associated with GVHD might be of pathogenetic significance. Am. J. Hematol. 77:200-202, 2004. ª 2004 Key words: squamous cell carcinoma; tongue; GVHD; HSCT The development of secondary malignancies is an important complication after haematopoietic stem cell transplantation (HSCT) and curtails the survival of patients otherwise cured of their original malignancies. The commonest secondary malignancies are therapyrelated myelodysplastic syndrome/acute myeloid leukemia, lymphomas, and solid tumors including squamous cell carcinoma (SCC), melanomas, and sarcomas [1].The occurrence of secondary malignancies has been attributed to cumulative toxicity of previous chemotherapy and radiotherapy. Risk factors include young age at the time of HSCT, and the use of total body irradiation during conditioning [1].We present two cases of carcinoma of the tongue, with chronic oral mucosal graft-versus-host disease (GVHD) as a possible risk factor. CASE REPORTS Case 1A 45-year-old man, non-smoker and non-drinker, presented with acute myeloid leukemia in 1995, which relapsed in 1996. Allogeneic HSCT was performed, the donor being an HLA-identical sister. The conditioning was busulphan (Bu), cyclophosphamide (Cy), and total body irradiation (TBI), with cyclosporine and methotrexate as GVHD prophylaxis. He developed severe GVHD affecting the liver as well as extensive oral mucosal and skin GVHD (grade III), requiring steroid, thalidomide, and azathioprine for control. Subsequently, chronic GVHD affecting the skin and mouth supervened. Six years later, an ulcerative growth at the dorsum of the tongue was found in a background of lichenoid mucositis, which on biopsy showed welldifferentiated SCC. The tumor was T3N0M0, stage III. Total glossectomy, right functional neck dissection, and left submandibular gland dissection was

Skin cancer after nonmyeloablative hematopoietic cell transplantation

“…[30][31][32] Adequate numbers of activated CD4 þ T-lymphocytes have been postulated to inhibit malignant transformation of precursor skin lesions. 33,34 Features of these observations of particular interest include the following: (1) there was a striking incidence of secondary skin cancers; (2) the secondary skin cancers appeared relatively early after intense, short-term immunosuppression, which contrasts with that observed after solid organ transplantation; and (3) there was a predilection for patients with prior t-AML/MDS. This latter association is especially noteworthy, and suggests that patients with t-AML/MDS harbor a constitutional tendency towards the development of skin cancer.…”

Orofacial diseases in solid organ and hematopoietic stem cell transplant recipients

“…The major and most serious consequence of oral lichenoid lesions of GVHD is oral squamous cell carcinoma (Abdelsayed et al , 2002; Szeto et al , 2004; Curtis et al , 2005; Demarosi et al , 2005; Sato et al , 2006). The 25‐year oral cancer incidence of 1.0–1.8% reported among HSCT recipients with cGVHD (Leisenring et al , 2006) is similar to the malignant potential of oral lichen planus in other patients.…”

Graft-versus-host disease

“…17,[35][36][37]38 The long-term risk of melanoma in pediatric patients receiving HCT may be associated with a conditioning regimen using high doses of alkylating drugs. 36 Patient age, actinic exposure, skin phototype, and previous ionizing radiation are additional risk factors in the development of nonmelanoma skin cancers after HCT 39,40 (Fig 3).…”