Diffusely Scattered Macules Following Radiation Therapy

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

A, Histopathology revealed dermal perivascular aggregates of mast cells (H&E, original magnification ×200). B, Higher magnification demonstrated the typical basophilic granular cytoplasm and the bland round-oval dark basophilic nuclei of mast cells (H&E, original magnification ×200). C, Dermal mast cells were highlighted by CD117 immunohistochemical stain (original magnification ×200).

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.