January 2000, Volume 50, Issue 1

Case Reports

Immunosuppresive Drug therapy as a Potentiator of Anal Carcinoma in a Patient with Relapsing Lymphoma

K.R. Makhdoomi  ( Department of Surgery, Victorial Hospital, Kirkcaldy. )
B.J.P. Huntly  ( Department of Haematology, Ninewells Hospital, Dundee. )
R.T. Diggory  ( Department of Surgery, Victorial Hospital, Kirkcaldy. )

Introduction

Anal carcinoma represents 5% of the anorectal cancers, Its aetiology is linked to a number of different predisposing factors, among which the most recent and widely accepted is the Human Papilloma Virus (HPV). The multifactoral aetiology suggests that development of tumour depends on the synergy between this virus, carcinogens and the immunological status of the patient. We report a case that illustrates these points.

Case Report

A 35 year old man presented with multiple perianal skin tags for which an excision biopsy was performed. Subsequent histology revealed the presence of wide spread dysplastic change of Bowens disease with areas of well differentiated keratinising squamous cell carcinoma. The immunoperoxidase staining for HPV was strongly positive. He was HIV negative and had stage lIa Hodgkin’s disease in 1983, which was treated with upper mantle radiotherapy. Five years later he relapsed with recurrence in the liver and spleen, which was treated initially with Epirubicin Vinblastine and Bleomycin, but due to pyrexial reactions it was changed after two courses to Chiorambucil, Procarhazine, Vincristine and Prednisolone. Seven such courses were given achieving complete remission. He had a further relapse : ear later in the middle zone of his right lung, with no evidence of disease elsewhere and received 3 courses of intensive multidrug regime chemotherapy which included Etoposide, Vinbiastine, Chiorambucil and Procarbazine, with which he again achieved complete remission. This treatment was followed by autologus marrow transplant, conditioned with a single dose of Etoposide and Meiphelan. Two years later he relapsed for the third time in the same pulmonary area and on this occasion was treated with 10 fractions megavoltage radiotherapy to the lung field followed by 5 courses of CCNU and Vindesine achieving remission.

Discussion

Anal carcinoma is rare, being 20-30 times less common than colonic cancer and represents only 5% of anorectal cancers1. It occurs throughout the world but is particularly common in Brazil and India where the incidence of anal cancer is closely related to that of carcinoma of cervix, penis and vulva, suggesting a common aetiological factor2.
The aetiology of anal cancer is not well understood, but is presumed to be multifactorial, representing an interaction between genetic and enviornmental factors3. Several predisposing factors are related to anogenital carcinoma like smoking, sexual orientation, viral warts, human papilloma virus infection, immune status and tumor suppresser genes3,4. The case discussed illustrates the interaction of these factors in the development of anal carcinorn a.
There is evidence that Hodgkin’s disease predisposes the patient to HPV infection and that about 6% of such patients acquire its. HPV infection alone is insufficient to cause malignant transformation and only a small proportion of patients with HPV eventually develop tumours4. It has therefore been hypothesised that HPV may act as promoter in synergy with carcinogenic initiators, such as cigarette smoking or exposure to radiation4. The expression and detection of HPV is modulated by the immune status of the host and an increased prevalence of HPV is known to occurs during the mild and transient immune deficiency of pregnancy6. Similar trends have been seen with iatrogenic immune suppression in patients with renal transplant7 cardiac a! lograft recipients, patients after chemotherapy7,8 and in homosexual men with human immunodeficiency virus infection9,10. Secondary neoplasms have been reported by LokichU in patients who received chemotherapy for Hodgkin’s disease, but these patients were not infected with HPV. We suspect that immunosuppression in our patient after multiple courses of chemotherapy caused expression of HPV which he acquired during the course ot his Hodgkin’s disease. HPV is synergy with radiotherapy resulted in the development of anal carcinoma. He was later treated with radical radiotherapy and there has been no evidence of recurrence of his anal carcinoma to date.
It is therefore recommend that special attention should be paid to the anogenital area of such immuosuppressed patients during follow-up. Any papillomata in the area should be regarded carcinoma until proved otherwise by biopsies.

References

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3.Holly BA, Whitiemore AS, Aston DA, et at. Anal cancer incidence: genital warts, anal fissure or fistula, haemorroids and smoking. J. Natl. Cancer Inst., 1989:81:1726-31.
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6.Schneider A, I-lotz M, Gissman L.. Increased prevalence of human papillomavirus in the lower genital tract of pregnant women. Ins, J. Cancer. 1987;4 0: 198-201.
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8.Krebs HB, Schneider V, Hurl WG. ci al. Genital condytonias in immunosuppressed women, a therapeutic challenge. South Med. J., 1986:79:183-87.
9.Frazer lH, Medley C, Crapper RM, et at. Association hetween anoreetal dyspl asia, human papi I loins virus and human imm nnodelicmenev virus infection in lionmosexual men. Laneet, 1986:2:657-60.
10.Palefsky JM, Gonzales J, Greenblatt RM. el al. Anal intraepithelial neoplasia and anal papillomavirus ain tèction among homosexual males wi th group IV HIV disease. JAMA: 1990:263:291:1-16.
11.Lokich JJ. Secondary uncommon solid neoplasms in cured H odgkins’s disease and follow-up of the original B-DOPA ehemotherpay patient group. Am. i. Clin. Oneol., 1990;13:247-50.

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