Xeroderma pigmentosa in siblings: Cystosarcoma phylloides in a case of xeroderma pigmentosa

Introduction

Xeroderma pigmentosa (XP) is a rare autosomal recessive disease with numerous neoplasms on sun exposed areas of the skin and eyes because of an inability to repair the ultra -violet radiation inflicted damage to DNA.[1] Kenneth H Kraemer et al in 1987 compiled 830 cases of XP reported in 297 articles obtained from a survey of medical literature from all over the world; of which 29 cases were reported from India.[2] Goyal et al reported 10 cases of various oculocutaneous manifestatins in XP from JIPMER, India in 1994.[3] Apart from oculocutaneous neoplasms the XP is rarely associated with neoplasms of other organs like brain, bone marrow, stomach, testes, lungs, pancreas ets However no case of XP in association with cystosarcoma phylloides is reported till date. Here we are reporting two siblings of a consanguinously married normal couples; a male who has already undergone treatment for 36 oculocutaneous neoplasms and a female (sister of the former) who had 12 oculocutaneous neoplasms and a cystosarcoma phylloides in her right breast.

Case Reports

Case 1:A male, born in 1972 had the first symptom of XP at the age of 3 years in the form of acute sun burns with itching following brief exposure to sunlight and started developing multiple hyper-pigmented lesions all over the body except armpit and the perineum and he simultaneously developed photophobia and conjunctival injection. The chain of oculoailaneous malignancies started at the age of 13 years with (1) squamous cell carcinoma of right eyelid, (2) squamous cell carcinoma of scalp (3) keritinising verrucous carcinoma of the left ear which were treated by wide excision biopsy. This was relentlessly followed by many squamous cell carcinomas, basal cell carcinomas, basosquamous carcinoma, malignant melanomas and keratoacanthomas in varied regions which were treated according to the feasibility with wide excision and primary closure, wide excision and split skin grafting and/or radiotherapy. From the age of 13 years to 26 years he had 36 malignancies; 16 in head and neck, 9 in upper limbs, 8 in lower limbs and 3 over the trunk, Out of 36 malignancies 25 were squamous cell carcinomas, 8 were basal cell carcinomas 2 were malignant melanomas and 1 baso squamous carcinoma. At the age of 20 years he developed exposure keratitis, corneal ulceration and corneal opacity and blindness in the left eye following excision of a lower eyelid tumour. The thirty sixth malignancy which was a malignant melanoma in the left upper arm with lymph nodal metastasis in the axilla which was adherent to the axillary vein; eventhough excised by shaving it off from the vein. the residual growth eroded the vein within three weeks of surgery before radiotherapy could be given; and the death due to torrential haemorrhage ended the 20 year old agony.

Case 2A female, the sister of case 1 started developing photophobia and photosensitivity on exposure to sum at the age of 2 years and gradually developed the typical lesions of macular hyperpigmented lesions all over the body except arm pits and perineum. These lesions progressively involved every inch of the body surface. The patient had persistant bilateral injection of the limbal conluctiva and minimal corneal opacity from the age of 10 years. At the age of 12 years she developed a basal cell carcinoma of the right lower eye lid; and since then she has been coming regularly to the hospital fortreatment. She is now 22 years and has already undergone treatment for 12 malignancies of which 9 were in head and neck, 2 in upper limbs and 1 in the lower limb. Out of the 12 malignancies 4 were basal cell carcinomas, 5 squamous cell carcinomas, 3 malignant melanomas. Because of the ectropion of the right lower eyelid [Figure - 1] following excision of a squamous cell carcinoma, the patient developed corneal opacity and there was gross diminision of vision in the right eye.

Recently she developed a firm nodular lump [Figure - 2] in the right breast measuring 4cm x 5cm; the fine needle aspiration biopsy (FNAB) of which was reported as fibroadenoma. The histopathological report of the same after excission was benign cystosarcoma phylloides. [Table - 1]

Oculocutaneous manifestations of the two cases are tabulated below in almost the similar lines as done by JL Goyal et al.[3]

Discussion

Xeroderma pigmentosa (XP) is an autosomal recessive disorder associated with multiple oculocutneous and neurological manifestations due to defective DNA repair. The defective repair of the ultraviolet damaged DNA was first recognised by Cleaver JE in 1968.[1]

Though delayed skin changes are reported, usually erythematosis of the skin following brief exposure to the sunlight occurs by the age of two years.[4] Because of the defective DNA repair the sun activated melanocytes produce more melanin resulting in irregular 1 to 2 mm sized hyperpigmented macular lesions are also called freckles. These are associated with achromic hypopigmented areas due to mutated melanocytes which are unable to produce melanin.[6] Because of the mutated epidermal cells all known cutaneous malignancies may start appearing in the sun exposed areas as early as the first decade of life.[6]

Photophobia early in the course of the disease with circumlimbal conjunctival injection and timbal tumours are quite common. The lower eyelid neoplasms are more common than the upper eyelid neoplasms.[3] Either ectropion or entropion following surgical treatment of the eyelid neoplasms lead to exposure keratitis, pterygeum, corneal opacities may ultimately result in loss of vision.[3]

Kenneth et al in their survery of 830 cases encountered one case each of astrocytoma, medulloblastoma, sarcoma of the brain, acute lymphatic leukaemia, myelogenous leukaemia, choroidal leukaemia, pancreatic adenoma, testicular carcinoma, carcinoma stomach, and 2 cases of bronchogenic carcinoma.[2]

The female patient had a breast lump, the fine needle aspiration cytology of which was reported as fibrodenoma and later the excised lump was subjected to histopathological examination and the same was reported as cystosarcoma phylloides. On reviewing the literature (Medline R Computer Search) hitherto there was no case of cystosarcoma phylloides reported in association with XP.

The general line of management followed in these patients were measures to avoid exposure to harmful effects of ultraviolet rays of the sun, fluorescent lamps (tube light) which may emit ultraviolet rays and application of sunscreens to the skin. All the malignancies/ benign tumours were treated in the same way as in any other individual. Radiotherapy with ionising radiation was given wherever feasible as the patients can repair the DNA damage caused by this type of radiation. The patients should be asked to avoid carcinogenic substances like tobacco.