Squamous Cell Cancers of Head and Neck in Survivors of Allogenic Hematopoietic Stem Cell Transplantation

Background:The risk of secondary malignancies (SM) is increased in long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). There is limited literature on squamous cell carcinoma (SCC) of head and neck post-SCT. We report a single center series of 6 patients (pts) who developed SCC of oral cavity or esophagous during remission after SCT.

Methods:This IRB approved retrospective analysis reviewed charts of adult pts who had undergone SCT and subsequently developed SCC. Patients were identified by reviewing BMT data base and data was collected from medical records.

Results: Six patients (Table 1), median age 40 yrs (31-54) at SCT were diagnosed with SCC in a median follow up of 8 yrs (3-13). Five out of 6 pts developed SCC of tongue and 1 developed esophageal SCC. Five pts had chronic GVHD but had no history of alcohol or tobacco use except 1 pt (pt 6) who had remote history of smoking/alcohol use. Humanpapilloma virus was negative on the tumor samples. All pts had chronic inflammation, pain and intermittent ulcerations. New onset of oral pain was the main symptom in pts who developed oral SCC. Clinically oral SCC lesions look similar to chronic GVHD lesions. Three pts developed recurrences and 2 died of metastatic SCC.

Table 1. Characteristics of squamous cell carcinoma in survivors of SCT

Patient	Age at SCT/sex	Primary Hematologic malignancy	Type of SCT	Site/stage of SCC	Resection margin	LVI/PNI	Preceding lesions	Chronic GVHD	Chronic GVHD treatment
1	46M	Non-Hodgkin’s Lymphoma	RIC MSD	Right tongue, left floor of mouth, pT1N0	+	-/-	SD	Oral	C+P+Ph+R
2	40M	AML	Ablative MSD	Base of tongue and left tonsil, pT1N1	+	+/-	NPB	-	-
3	35F	AML	Ablative MSD	Left tongue,  pT2N0	+	-/+	SD	Oral	P+M+Ph
4	54F	CML	Ablative MSD	Right tongue, pT4aN2b	+	-/+	SD	Oral	P+M
5	42M	CML	Ablative MSD	Tip of the tongue, pT1Nx	+	-	NPB	Oral	P+M+Ph
6	31M	CML	Ablative MSD	Gastroesophageal junction, stage IIIA	NA	-/-	SD	Oral, esophageal	P+M+Ph+R

RIC indicates reduced intensity conditioning, MSD matched sibling donor, MUD matched unrelated donor, LVI lymphovascular invasion, PNI perineural invasion, SD squamous dysplasia, NPB no prior biopsy, NA not applicable, NP not performed, C cyclosporine, P prednisone, M mycophenolate mofetil, R Rituximab, Ph photopheresis

Conclusion: Our observation shows that the SCC of oral cavity is a common SM in post-SCT patients. SCC was often multifocal, negative surgical margin was difficult to obtain and employing standard therapy was difficult due to concomitant severe chronic GVHD. The SCC lesions were clinically indistinguishable from chronic GVHD lesions and the only presenting clinical symptom was a new onset of persistent oral pain from a non-healing GVHD-like lesion. Since SCC in this setting can mimick a GVHD lesion, a non-healing oral lesion should not be assummed to be chronic GVHD. Such lesions should be evaluated in consultation with ENT and a biopsy considered to rule out SCC.