Basal Cell Carcinoma with Xeroderma Pigmentosum in an 8-Year-old Girl.

Sir,

An 8-year-old girl, known case of xeroderma pigmentosum (XP), a presented with poikiloderma consisting of skin atrophy, telangiectasias, and mottled hyperpigmentation and hypopigmentation on the face, neck, and forearm that is to say on sun-exposed areas [Figure 1b]. She developed ulcerated lesions on both sides of the nose measuring 1 cm × 1 cm and 1 cm × 0.5 cm which appeared 2 months back [Figure 1a]. She had a history of diffuse erythema, scaling, and freckle-like areas of increased pigmentation on exposure to the sun when she was 3 years old which would tend to diminish during the winter months with decreased sun exposure. These features became permanent with the passage of time. She also complained of photophobia, but there were no apparent ocular complications. On physical examination, the child was conscious, cooperative, average built. Neurological examination was normal. Other investigations were within normal limits. She did not have a family history of the disorder. Her siblings were well and showed no signs of any illness. There was clinical suspicion of secondary malignancy. She was operated upon for the ulcerated lesions on the nose, and a biopsy was sent to the pathology laboratory.

Figure 1

(a) Close-up of the lesion. (b) Xeroderma pigmentosum

Histopathological findings

Tissue is lined by epidermis which is atrophic at places with loss of rete ridges. At other places, acanthotic epithelium is noted with downward proliferation of rete ridges. Hyperkeratosis, ulceration, and hemorrhagic areas are also noted. Dermis reveals the presence of scattered dysplastic cells along with giant cells. Dilated and congested vessels are also present. The above mentioned histopathological findings are suggestive of basal cell carcinoma (BCC). We referred the patient to a pediatric oncologist [Figure 2a and b]. The pediatric oncologist advised for the regular follow-ups. We advised the parents to avoid direct sunlight and unnecessary radiation exposures such as X-ray and computed tomography. The patient is lost to follow-up after 3 months.

Figure 2

Histopathology slides. (a) Nests of basal cell with peripheral palisading in the stroma and plasma infiltration. (b) Black arrow shows mitosis and blue arrow shows peripheral palisading

XP is characterized by extreme photosensitivity leading to early actinic damage and risk of cutaneous neoplasms. Patients with XP have defective nucleotide excision repair of DNA damages induced by ultraviolet (UV) rays.[1] So far, eight complementation groups (XPA through XPG and XP variant) have been identified. XP is an autosomal recessive disorder characterized by variably deficient repair of UV-induced photoproducts, and skin phenotype often manifests the dry leathery appearance of prematurely photoaged skin. They may also manifest as basal cell and squamous cell carcinomas (SCCs) and melanoma in the first two decades of life.

Multiple oculocutaneous malignancies are a common manifestation on sun-exposed facial areas in patients with XP. BCC and SCC are commonly seen which manifest in the early first decade in contrast to the fifth and sixth decades in the general population. Our patient is 8 years old.

Epidermal DNA, predominantly in keratinocytes and in Langerhans cells which are dendritic antigens presenting cells, absorbs UV-B and undergoes structural changes between adjacent pyrimidine bases (thymine and cytosine) including the formation of cyclobutane dimers and 6, 4-photoproducts. These structural changes are potentially mutagenic and are found in most BCC and SCC. They can be repaired by cellular mechanism that results in their recognition and excision and the restoration of normal base sequences.

XP has been found in all continents across all racial groups. Consistent with autosomal recessive inheritance, males and females are similarly affected. The incidence in India is lesser compared to the west and other Asian nations.[23] In the USA, the estimated prevalence of XP is at 1 in 250,000 and in Japan at 1 in 20,000.

Three clinical stages are recognized. Photosensitivity typically first manifests during the period from infancy to 3 years of age and is characterized by slight diffuse erythema and associated scaling followed by small areas of hyperpigmentation resembling freckles. Not all groups show severe photosensitivity. Photophobia and chronic conjunctivitis may be early presenting signs. In early childhood, the second stage presents with skin atrophy, mottled pigmentation, and telangiectasia, giving the skin an appearance similar to chronic severe actinic damage. Active keratoses arise in areas of scaling. The final stage is characterized by multiple secondary malignant tumors of the skin appearing in late childhood. The tumors include SCC, BCC, melanoma, and rarely fibrosarcoma and atypical fibroxanthoma. In some patients, neoplasms progress rapidly and represent the major cause of early mortality. The eyes are also progressively affected, showing conjunctivitis, keratitis with corneal opacities, and palpebral scarring. Ocular neoplasms may also occur which may need exenteration. Oral and visceral neoplasm occurs with a higher incidence in patients with XP.

The malignancies are seen in 50% of the patients in the first decade. Many risk factors are known to exacerbate the cutaneous features resulting in skin cancers and early death. These risk factors include sunny weathers, outdoor living, fair skin, smoking, poor availability of diagnostic facilities, delayed diagnosis, and poor protection from sunlight. However, early protection from UV radiation may prevent skin malignancy.

About 25%–30% of XP patients develop neurological manifestations in infancy or the second decade. Neurological manifestations are mostly associated with XPA gene mutation. Our patient does not have any neurological manifestation. The most common causes of death in XP patients are due to skin cancers, neurological degeneration, or internal malignancy.[4]

In the first stage, the histopathologic appearance is not specific, but the diagnosis is suggested by a combination of changes that normally are not seen in the skin of a young person. These include hyperkeratosis, thinning of the stratum malpighii with atrophy of some of the rete ridges and elongation of others, a chronic inflammatory infiltrate in the upper dermis, and irregular accumulation of melanin in the basal cell layer, with or without an increase in the number of melanocytes.

In the second stage, the above findings become more pronounced. The epidermis shows atrophy in some areas and acanthosis in others. There may be disorder in the arrangement of the epidermal nuclei, and in some areas, epidermis may show atypical downward growth. Hence, histologic picture in such areas is identical with that of an actinic keratosis. The upper dermis shows basophilic degeneration of the collagen and solar elastosis, as also is seen in solar degeneration.

The third stage of XP is characterized by various malignant tumors mentioned above.

Persons with XP must avoid exposure to sources of UV light and must wear protective clothing and UV-absorbing eyeglasses. Topical application of 5-fluorouracil or imiquimod is used for premalignant lesions, and surgical excision is done for malignant neoplasm of the skin, tongue, eyelids, conjunctiva, and cornea. Methylcellulose- or quinidine-containing eye drops and bland ointment are used in eye care.[5]

Since definitive treatment of XP is not well established, hence, genetic counseling and strict lifestyle restriction form the mainstay of management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.