Aggressive Squamous Cell Carcinoma in Kindler Syndrome

Abstract

A 57-year-old Hispanic man with a personal and family history of bullae and photosensitivity presented with a fungating, ulcerated squamous cell carcinoma on his left hand (Figure 1). Physical examination showed conjunctival injection, ectropion, symblepharon, urethral stricture, loss of teeth, short stature, and nail dystrophy. There was reticulated erythema, atrophy, hyperpigmentation and hypopigmentation, and telangiectasia of sun-exposed skin of the face, neck, and hands consistent with poikiloderma (Figure 2). In addition, there was foreshortening of the left thumb and sclerodermoid changes of his hands (Figure 3). Radiation therapy was applied to shrink the tumor before a local excision was performed. However, a local recurrence followed and axillary lymph nodes became clinically palpable, necessitating amputation and lymph node dissection. Extensive histologic evaluation of the specimen obtained following left arm amputation and lymph node dissection showed moderate-to-poorly differentiated deeply invasive squamous cell carcinoma. Two of 3 axillary lymph nodes were positive for metastatic carcinoma. A random biopsy of the trunk showed epidermal atrophy, telangiectasia, a perivascular lymphocytic infiltration, and pigment-laden macrophages consistent with poikiloderma. Electron microscopy illustrated extensive reduplication of the basement membrane, with loops, curls, and free extensions of the basal lamina in the superficial dermis; reduced numbers of hemidesmosomes and anchoring fibrils; and a basement membrane focally devoid of basal cells (Figure 4). On the basis of the clinical features and the characteristic basement zone changes, a diagnosis of Kindler syndrome was made.

The kindlin family: functions, signaling properties and implications for human disease

“…A direct consequence of the SC hyperactivation in KS is that patients also have a higher risk of developing skin cancer -mainly squamous cell carcinomas (SCCs) and often at an early age (Arita et al, 2007;Emanuel et al, 2006;Lotem et al, 2001;Mizutani et al, 2012). Although an impaired β1-integrin function has been shown to prevent the formation of skin tumors (Janes and Watt, 2006;Frank et al, 2005), aberrant Wnt and TGFβ signaling caused by loss of kindlin-1 is probably a important reason for the increased risk of tumor development (Beronja et al, 2013;Malanchi et al, 2008;Guasch et al, 2007).…”

Report of two rare cases of Kindlers syndrome in siblings

“…Blistering and photosensitivity improves with age whereas poikiloderma and atrophy, particularly on sun exposed sites worsens with progressing age 1,2,6 . Additional findings include telengiectasia, palmoplantar keratoderma, pseudo-ainhum, nail dystrophy, pseudosyndactyly, periodontal disease with erosive gingivitis 5,7 , gingival hypertrophy, leukokeratosis of lip and oral mucosa; oesophageal, anal, urethral and vaginal stenosis; squamous cell carcinoma of skin or mucosae may also occur 8,9,10 . Different types of visceral malignancies are reported in association with kindler's syndrome.…”

Invasive Squamous Cell Carcinoma of the Hand in a Patient with Kindler Syndrome: Case Report and Literature Review

“…These tumours are usually extremely aggressive. To our knowledge, this is the second case of metastatic aggressive squamous cell carcinoma of the hand reported in the medical literature (8). Other tumours have been associated with this syndrome including osteoma of the cranium, Wilms' tumour and transitional carcinoma of the bladder (6,10).…”

“…Moreover, stenosis of urethral, anal or esophagal mucosa along with syndactylism have been reported (9). Actinic keratosis and squamous cell carcinoma have been described a few times, presenting particularly on the lips (6), soft palate (7) and hands (6,8). These tumours are usually extremely aggressive.…”