A Male Patient with Humoral Hypercalcemia of Malignancy (HHM) with Leukocytosis Caused by Cutaneous Squamous Cell Carcinoma Resulting from Recessive Dystrophic Epidermolysis Bullosa

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin disorder. Although the patients are at risk for cutaneous squamous cell carcinoma (SCC), no case of cutaneous SCC derived from RDEB with humoral hypercalcemia of malignancy (HHM) has been reported. We present the first case report of a male patient with HHM with leukocytosis caused by cutaneous SCC resulting from RDEB. A 20-yr-old Japanese male patient with RDEB; the diagnosis was confirmed by electron microscopic examination, suffered an intractable skin ulcer and hypercalcemia and leukocytosis. PTH-rP, SCC antigen and Granulocyte colony-stimulating factor (G-CSF) levels were elevated. The histological diagnosis of the skin lesion was made well-differentiated SCC. Immunohistochemical staining showed the expression of PTH-rP in atypical tumor cells. For the control of hypercalcemia before an amputation, we used zoledronate safely and could control the serum Ca concentration in the normal range. After the amputation of his right leg including SCC, leukocytosis improved immediately and PTH-rP in blood decreased to the normal range. One month after the amputation, local recurrence of cutaneous SCC and multiple lung metastases were observed. PTH-rP increased gradually associated with hypercalcemia. Although the patient reached an unfortunate turning point about 4 mo after the amputation, we propose that zoledronate is an effective and safe treatment for HHM with cardiorenal complications.

Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines

“…SCCs may arise at a young age in patients with EB, particularly those with RDEB‐SG. This complication has been described in a child as young as 6 years of age, and has been reported frequently in patients aged < 20 years . As the incidence of SCC increases with age in at‐risk forms of EB, and patients frequently develop multiple primary tumours, ongoing monitoring for patients with previous SCCs becomes even more important (Table ).…”

“…localized bony pain, deranged liver function tests, breathlessness), should undergo staging. Where available, FDG‐PET with CT scanning should be undertaken. In interpreting the results, it should be noted that in EB there may be nonspecific uptake of isotope on PET scanning from chronic skin wounds, reactive lymph nodes, the oesophagus and bone marrow, but combination with CT scanning can help to clarify the significance of increased uptake Where PET scanning is not available, a CT or magnetic resonance imaging scan of the chest, abdomen and pelvis may identify systemic or lymph node metastases. If CT scanning is unavailable, abdominal ultrasonography and/or bone scanning may help to identify systemic metastases. …”

“…Where the size or anatomical location of an EB SCC means that excision is not possible, it may be necessary to consider amputation of the digit or limb . (Strength of recommendation D, quality of evidence III.…”

A Rare Case of Hypercalcemic Crisis Secondary to a Squamous Cell Carcinoma Arising from a Nonhealing Ulcer

“…Only a few reports are available associating HHM with primary cutaneous SCC arising from the chest wall (1,2,4), burn scars (5,6), and decubitus ulcer (7). Some cases of SCC were associated with hidradenitis suppuritiva (8) or recessive dystrophic epidermolysis bullosa (9). To our knowledge, only one case of HHM secondary to SCC arising from a nonhealing leg ulcer without distant metastasis has been reported, thus highlighting the rare occurrence of this condition (10).…”

“…In the skin, it is highly expressed in external sheets of the pilous follicle, basal and granular stratum from epidermis and melanocytes and also normal keratinocytes and may have a significant role in follicular development (17). PTHrP has high affinity for the PTH/PTHrP receptor, through which it exerts its effects (9). PTHrP induces bone resorption and decreases bone formation, thereby affecting whole-body calcium distribution, resulting in hypercalcemia, while at the renal level, it stimulates phosphaturia and inhibits urinary calcium absorption (18).…”