Diagnostic Value of Calretinin in Mast Cell Lesions of the Skin

Abstract

The diagnosis of mast cell lesions of the skin can occasionally be challenging. Calretinin, a 29 kD neuron-specific calcium-binding protein found mostly in the CNS and retina, has been shown to be a positive marker for mesotheliomas, and is also expressed in mast cells. We studied the diagnostic value of calretinin and compared our results to other established ancillary studies used to identify mast cells, such as Toluidine blue and the Leder stain. Sixty-three cases were studied, including 45 mast cell lesions (22 urticaria pigmentosum, 17 mastocytomas, and six telangiectasia macularis eruptiva perstans [TMEP]), seven nevi, three melanomas, four granular cell minors of the skin, three cutaneous lymphomas, and one granulocytic sarcoma. Patients ranged in age from less than 1 to 85 years with a median age of 29 years. The group consisted of 36 females and 27 males. Calretinin was expressed in all 45 mast cell lesions. Negative staining for calretinin was seen in all skin lesions that potentially could be considered in the differential diagnosis of mast cell lesions such as nevi, melanomas, lymphomas, and the granulocytic sarcoma. However, calretinin expression was noted in four/four granular cell tumors. Leder and Toluidine blue stains were positive in all 45 mast cell lesions, and all nonmast cell lesions were negative with these stains. In conclusion, our study demonstrated that calretinin is a sensitive and specific marker of mast cells and can be an aid in distinguishing mast cell lesions from other skin lesions considered in the differential diagnosis. Calretinin may be more sensitive than the currently used special stains utilized to diagnose mast cell lesions having few diagnostic mast cells such as TMEP. However, this immunoperoxidase stain does not add significant diagnostic information in most cases, when compared with the currently used less expensive special stains and, therefore, is not cost-effective. Int J Surg Pathol 8(2):119-122, 2000

Value of Calretinin Immunostaining in Diagnostic Pathology

“…The first such study was by Sariya et al 155 who, in 2007, reported positive staining for calretinin in 12 (67%) of 18 primary adnexal carcinomas, whereas only 9 (28%) of 32 metastatic adenocarcinomas to the skin were positive for this marker. 11,48,68,142,147 These findings indicate that calretinin, in contrast to S100 protein, another member of the EF-hand family of calcium-binding proteins, is uncommonly expressed in these tumors. This is in contrast to a more recent study by Mahalingam et al 156 who were able to demonstrate calretinin positivity in only 8 (14%) of 59 primary adnexal carcinomas and 5 (10%) of 50 metastatic adenocarcinomas to the skin.…”

“…Among benign soft-tissue tumors, calretinin has been reported to be frequently expressed in lipomas (100%), myxolipomas (100%), spindle cell lipomas (75%), 68 Schwannomas (75% to 100%), 67,68,146 and granular cell tumors (93% to 100%). 11,67,147 It has also been reported, but with less frequency, in proliferative fasciitis (50%), 66 nodular fasciitis (23%), 66 benign fibrous histiocytoma (33%), 66 leiomyoma (0% to 27%), 11,54,55 and solitary fibrous tumor (0% to 13%). 11,61,66,148 Because calretinin is commonly expressed in Schwannomas, but not neurofibromas, some authors have suggested that positivity for this marker favors a diagnosis of Schwannoma over neurofibroma in those instances in which the differential diagnosis is difficult.…”

“…Early studies were unable to demonstrate calretinin expression in solitary fibrous tumors 11 and because of this, it was suggested that immunostaining for this marker may have some utility for assisting in discriminating these neoplasms from sarcomatoid mesotheliomas as a relatively large percentage of the latter tumors are calretinin positive. 11,23,48,54,55,61,[66][67][68]87,130,142,[146][147][148]150,152,153 In Table 7 are summarized the results of some of the published studies on calretinin expression in soft-tissue tumors.…”

Calretinin expression in tumors of adipose tissue

“…Anticalretinin stained slides were evaluated for the extent (expressed as an approximate percentage of positive cells) and distribution of specific staining. Intralesional mast cells, known to be calretinin positive [4,5,24,25], were commonly observed but not scored in the analysis. In several sarcomas, scattered reactive-appearing cells were identified by calretinin staining.…”

Calretinin

“…5,9 Calretinin has been also reported to be expressed in mast cells and related lesions. 5,10 In the largest tissue microarray analysis of more than 5,000 samples, calretinin expression was detected in small number of tumors from skin (including squamous and basal cell carcinomas, malignant melanoma, and Merkel cell carcinoma), lung (most commonly small cell carcinoma followed by squamous cell carcinoma), digestive (salivary gland tumors, stomach, small and large intestine adenocarcinomas) and genitourinary tract (most commonly testicular Leydig cell tumor and bladder small cell carcinoma), brain, soft tissues (largely in granular cell tumors and leiomyoblastomas), and neuroendocrine tumors (adrenal cortical adenomas, appendiceal carcinoid, and medullary carcinoma of the thyroid). 9…”