Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome

Abstract

Importance: Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature.

Objective: The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome.

Design: This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology.

Main outcome and measures: The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature.

Results: The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome.

Conclusions and relevance: The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

Figure 1.. Clinical Features of Histiocytoid Sweet Syndrome

A, Tender erythematous plaques on the back, some of them with annular morphology showing a raised erythematous border and a slightly depressed violaceous center. B, Painful erythemato-edematous plaques on the palms.

Figure 2.. Histopathologic and Immunohistochemical Features of Histiocytoid Sweet Syndrome (Case 8)

A-C, Hematoxylin-eosin–stained specimens. A, Scanning power shows edema and nodular infiltrates in the superficial dermis. B, The infiltrate is close to the epidermis, but there is no exocytosis. C, The nodules are mostly composed of mononuclear cells with twisted vesicular nuclei and scant eosinophilic cytoplasm. D-F, Double immunostained specimens (myeloid nuclear differentiation antigen [MNDA, black] and myeloperoxidase [MPO, red]). D, Scanning power. E, With this double immunostain, exocytosis of single cells is more evident than with hematoxylin-eosin. F, Most of the cells of the infiltrate coexpress MNDA in their nuclei and MPO in their cytoplasm. G-I, Double immunostained specimens (MNDA [black] and CD163 [red]). G, Scanning power. H, With this double immunostain, most of the cells express MNDA in their nuclei, while less scattered cells express CD163 in their cytoplasm. I, Higher magnification demonstrates that cells expressing CD163 in their cytoplasm do not express MNDA in their nuclei.

Figure 3.. Histiocytoid Sweet Syndrome in a Patient With Chronic Myelogenous Leukemia (Case 1)

A, Clinically, the lesions occurred on the lower extremities and were annular with an erythematous border. B and C, Hematoxylin-eosin–stained specimens. B, Histopathologic features consist of edema in the papillary dermis and a bandlike infiltrate in the superficial dermis; there are also perivascular infiltrates around deep dermal vascular plexus. C, At higher magnification, the predominant cells of the infiltrate are mononuclear cells with vesicular twisted nuclei and scant eosinophilic cytoplasm; nuclei are slightly pleomorphic, and there are some mitotic figures. D and E, Double immunostained specimens (myeloperoxidase [MPO, red] and CD163 [black]). D, Scanning power. E, At higher magnification, most cells express MPO, and very few cells at the periphery express CD163. F and G, Double immunostained specimens (MPO [red] and myeloid nuclear differentiation antigen [MNDA, black]). F, Scanning power. G, At higher magnification, most cells of the infiltrate coexpressed MNDA in their nuclei and MPO in their cytoplasm. H and I, Double immunostained specimens (MNDA [black] and CD163 [red]). H, Scanning power. I, At higher magnification, most cells of the infiltrate expressed MNDA in their nuclei, whereas some cells at the periphery expressed CD163 in their cytoplasm; no cells coexpress both markers. J and K, Double immunostained specimens(MNDA [black] and CD14 [red]). J, Scanning power. K, At higher magnification, the cells of the nodules express MNDA in their nuclei, whereas cells expressing CD14 in their cytoplasm are at the periphery of the nodules. L and M, Double immunostained specimens (MNDA [black] and CD34 [red]). L, Scanning power. M, At higher magnification, most cells of the infiltrate express MNDA in their nuclei, whereas only endothelial cells of the blood capillaries express CD34 in their cytoplasm. N, By fluorescent in situ hybridization, single scattered cells show red-green bcr/abl fusion signal (circled); these cells are interpreted as leukemia cells intermingled with nonneoplastic cells of histiocytoid Sweet syndrome.