Squamous cell carcinoma-like giant keratoacanthoma with delayed presentation in a known case of xeroderma pigmentosum

Introduction Keratoacanthomas are rapidly growing cutaneous tumours, which usually resolve leaving an atrophic scar. The term ‘giant keratoacanthoma’ is applied to a lesion greater than 2–3 cm in diameter. This case report discusses squamous cell carcinoma-like giant keratoacanthoma with delayed presentation in a known case of xeroderma pigmentosum. Case report A 50-year-old female patient, a known case of xeroderma pigmentosum, presented with a large, domeshaped, crateriform lesion over her right cheek that had persisted for the last four months. Histological examination showed an exophytic lesion with a large central keratin-filled crater surrounded by deep bulbous nodules of proliferating squamous cells that had abundant keratin with a lip of normal epidermis. The demarcation was discrete except for tiny foci of deep infiltration at the periphery. However, immunohistochemistry for p53 revealed strong positivity only in the basal layer of the infiltrating islands, weak Ki-67 and desmoglein positivity, along with down regulation of Bcl-2 and E-cadherin. Followup for 18 months did not reveal any site recurrence or metastasis. Conclusion This case highlights the uncommon, delayed, adult onset presentation of giant keratoacanthoma with borderline histological features that mimic squamous cell carcinoma but show negative immunohistochemistry. Introduction Keratoacanthoma (KA) was first described in 1889 by Sir Jonathan Hutchinson as a ‘crateriform ulcer of the face’. KAs are rapidly growing, cutaneous tumours with atypical histological features similar to squamous cell carcinoma (SCC) that resolve leaving an atrophic scar1. KAs are either follicular KAs arising in hair-bearing skin or non-follicular KAs arising in the palm and sole2. Nearly all KAs are solitary lesions, less than 2 cm in diameter and arising on skin exposed to the sun. The term ‘giant keratoacanthoma’ is applied to a tumour greater than 2–3 cm in diameter2. Xeroderma pigmentosum (XP) is a rare, autosomal recessive genodermatosis characterised by deficient DNA repair, photophobia, severe solar sensitivity, cutaneous pigmentary changes and xerosis developing before the age of two years. Early development of mucocutaneous and ocular lesions, solar keratoses, cutaneous horns, KA, SCC and basal cell carcinoma, basosquamous carcinoma, atypical fibroxanthoma, malignant melanomas and angiomas, have been reported2. We present a case of a 50-year-old female patient, a known case of XP, with a large, solitary dome-shaped lesion on her right cheek. Case report A 50-year-old female patient, a known case of XP, presented with a large, solitary, dome-shaped lesion on her right cheek that had been rapidly growing for the past four months. There was no lymphadenopathy. Fine needle aspiration cytology showed only nucleated and anucleated squames. Surgery was performed with wide skin margins and the specimen was sent for histopathological examination with clinical suspicion of SCC. Gross A single skin-covered soft tissue mass measuring 6.5 × 6 × 3.5 cm in size, was received. An ulcero-proliferative growth was identified 1.2 cm and 0.7 cm from both lateral margins and 0.5 cm and 0.2 cm from both vertical margins. Cut surface was grey white and firm with central necrosis. Procedure The tissue was paraffin-embedded and stained by haematoxylin and eosin. Immunohistochemistry was done on the paraffin sections by the antibodies as indicated in the text. Histological examination showed an exophytic lesion with a central keratin-filled crater surrounded by solid lobules of proliferating squamous cells with abundant keratin. A lip of normal epidermis was seen at the peripheral edge. Parakeratosis within the crater and micro-abscesses were seen towards the periphery. The cells showed mild anisonucleosis, prominent nucleoli and infrequent mitosis. The advancing edges at the base and sides of the lesion were distinct except for focal irregular areas with cords of squamous cells infiltrating the underlying dermis. A dense lymphocytic infiltrate admixed with polymorphs and eosinophils, was seen at most of the tumour interphase, however, the infiltrate was lymphoplasmacytic in the infiltrative areas (Figure 1). Additionally, immunohistochemistry for p53 revealed strong positivity only in the basal layer of infiltrating islands with weak Ki67 staining. Loss of Bcl-2 and E-cadherin but preserved desmo* Corresponding author Email: nigamjs@gmail.com D.D.U. Hospital, New Delhi, India De rm at ol og y


Introduction
Keratoacanthoma (KA) was first described in 1889 by Sir Jonathan Hutchinson as a 'crateriform ulcer of the face'.KAs are rapidly growing, cutaneous tumours with atypical histological features similar to squamous cell carcinoma (SCC) that resolve leaving an atrophic scar 1 .KAs are either follicular KAs arising in hair-bearing skin or non-follicular KAs arising in the palm and sole 2 .Nearly all KAs are solitary lesions, less than 2 cm in diameter and arising on skin exposed to the sun.The term 'giant keratoacanthoma' is applied to a tumour greater than 2-3 cm in diameter 2 .Xeroderma pigmentosum (XP) is a rare, autosomal recessive genodermatosis characterised by deficient DNA repair, photophobia, severe solar sensitivity, cutaneous pigmentary changes and xerosis developing before the age of two years.Early development of mucocutaneous and ocular lesions, solar keratoses, cutaneous horns, KA, SCC and basal cell carcinoma, basosquamous carcinoma, atypical fibroxanthoma, malignant melanomas and angiomas, have been reported 2 .We present a case of a 50-year-old female patient, a known case of XP, with a large, solitary dome-shaped lesion on her right cheek.

Case report
A 50-year-old female patient, a known case of XP, presented with a large, solitary, dome-shaped lesion on her right cheek that had been rapidly growing for the past four months.There was no lymphadenopathy.Fine needle aspiration cytology showed only nucleated and anucleated squames.Surgery was performed with wide skin margins and the specimen was sent for histopathological examination with clinical suspicion of SCC.

Gross
A single skin-covered soft tissue mass measuring 6.5 × 6 × 3.5 cm in size, was received.An ulcero-proliferative growth was identified 1.2 cm and 0.7 cm from both lateral margins and 0.5 cm and 0.2 cm from both vertical margins.Cut surface was grey white and firm with central necrosis.

Procedure
The tissue was paraffin-embedded and stained by haematoxylin and eosin.Immunohistochemistry was done on the paraffin sections by the antibodies as indicated in the text.
Histological examination showed an exophytic lesion with a central keratin-filled crater surrounded by solid lobules of proliferating squamous cells with abundant keratin.A lip of normal epidermis was seen at the peripheral edge.Parakeratosis within the crater and micro-abscesses were seen towards the periphery.The cells showed mild anisonucleosis, prominent nucleoli and infrequent mitosis.The advancing edges at the base and sides of the lesion were distinct except for focal irregular areas with cords of squamous cells infiltrating the underlying dermis.A dense lymphocytic infiltrate admixed with polymorphs and eosinophils, was seen at most of the tumour interphase, however, the infiltrate was lymphoplasmacytic in the infiltrative areas (Figure 1).Additionally, immunohistochemistry for p53 revealed strong positivity only in the basal layer of infiltrating islands with weak Ki67 staining.Loss of Bcl-2 and E-cadherin but preserved desmo- glein was uniformly noted in all areas (Figure 2).Eighteen months follow-up did not reveal any local recurrence or metastasis favouring the diagnosis of giant KA with borderline features mimicking SCC.

Discussion
KA is seen in 3% of all reported cases of XP but giant KA is uncommon 3,4 .KA is a self-limiting epithelial proliferation with a strong clinical and histopathological similarity to welldifferentiated SCC.Exposure to excessive sunlight is the most frequently incriminated factor in the aetiology of both KA and XP with 95% of the solitary lesions found on the sun-exposed areas like the face, head and extremities 3,4 .
Men are more commonly affected than women.Lesions pass through the stage of proliferative phase, maturation phase and final resolving phase in which KAs reabsorb and expel the keratogenous core and eventuate into a scar with variable atrophy 1 .However, this case showed a rapidly increasing size with no involution.Kern et al. 5 observed that almost all of the confirmed KAs had invaginating keratin-filled craters with epidermal proliferation at the sides and the bottom of the lesion, and significant atypia and mitotic activity was rare, while SCCs showed considerable cellular anaplasia, pleomorphism and many displayed significant mitotic activity unlike this case 5 .Cribier et al. 6 evaluated 14 histological criteria, mainly based on the architecture of the tumours to differentiate KA from SCC. Epithelial lip, (as seen in this case) and sharp demarcation between tumour and stroma have been described as distinctive features of KA.However, this demarcation was focally not seen in this case thus increasing the difficulty in ruling out SCC.It was also suggested that atypical or difficult cases should be treated as SCC as clear-cut distinction is not possible in such cases; however, a clear distinction and diagnosis were made in this case 6 .
Cain et al. 7 compared the clinical, histological and immunohistochemical differences using antibodies to proliferating cell nuclear antigen, and wild-type and mutant-type p53 protein but found no significant statistical differences 7 .However, Kerschmann et al. 8 observed that 80% KA showed nuclear staining with anti-p53 antibody that was distributed along the outermost layers of the aggregates of neoplastic cells, similar to what was observed in our case, while 60% of the SCCs were uniformly p53 positive.Mean Ki-67 proliferation fraction was higher for KA than for SCC (55% vs. 46%), but this difference was not statistically significant 8 .Connolly et al. 9 concluded that immunohistochemistry for p53 and Ki-67 may help distinguish between a subungual SCC and a subungual KA 9 .Loss of Bcl-2 expression with tumour maturity in KA has been reported as seen in this case 10 .The use of a panel of immunoperoxidase stains for apoptosis-associated proteins, telomerase-associated protein and the cell adhesion protein E-cadherin, helped to conclude that KA has a different pathogenesis and biochemistry from that of SCC and is thus a distinct entity 1 .Desmoglein 1 and 2 have demonstrated the down regulation * Corresponding author Email: nigamjs@gmail.comD.D.U.Hospital, New Delhi, India Dermatology Licensee OA Publishing London 2013.Creative Commons Attribution Licence (CC-BY) F : Sood N, Nigam JS.Squamous cell carcinoma-like giant keratoacanthoma with delayed presentation in a known case of xeroderma pigmentosum.OA Case Reports 2013 Apr 01;2(3):29.

Figure 1 :
Figure 1: a. Central keratin-filled crater surrounded by an epidermal lip (H&E 100×).b.Solid lobules of proliferating squamous cells in the base with abundant keratin (H&E 100×).c.Solid lobules of proliferating squamous cells in the base with lymphocytic infiltrate at the interface (H&E 400×).d.Focal irregular areas with cords of squamous cells infiltrating the underlying dermis with lymphoplasmacytic infiltrate at the interface (H&E 400×).