ECH is a rare dermal neoplasm and is generally considered to be a morphological variant of FH. However, our case and recent reports suggest that ECH is actually a distinct entity, which displays a characteristic morphology, ALK immunopositivity, and ALK gene rearrangement. The differential diagnoses for ALK-positive tumors of the skin include ALK-positive anaplastic large cell lymphoma (ALK+ALCL) with or without systemic involvement  and Spitz tumors with ALK fusion . Since the cells of both of these tumors sometimes show histiocytoid or epithelioid arrangements, immunohistochemical panels including lineage-specific markers are critical for making a diagnosis of ECH. ALCL is always positive for CD30 and some T-cell markers, such as CD3, CD4, and cytotoxic molecules, whereas Spitz tumors are positive for melanocytic markers, such as melan A, MITF, and SOX10.
After first being identified in ALCL, ALK has been proven to be a versatile oncogene, which contributes to a variety of tumors, including those derived from hematolymphoid, epithelial, mesenchymal, melanocytic, and neural lineages [15, 16]. Alterations in the ALK gene can occur through various different mechanisms, including chromosomal translocation, point mutations, and amplification. In chromosomal translocation, ALK fusion proteins lead to ligand-independent constitutive activation of key pathways for oncogenesis and tumor progression.
It is interesting that each type of ALK-positive skin tumor seems to harbor a different common fusion gene. The findings of Jedrych et al.  and our data indicate that the SQSTM1-ALK can be a recurrent fusion gene in ECH. The most recent large studies by two groups also suggest that SQSTM1-ALK is the most common fusion gene in ECH, followed by VCL-ALK [10, 11]. Other minor fusion partners include DCTN1, ETV6, PPFIBP1, SPECC1L, TMP3, PRKAR2A, MLPH, and EML4 [10, 11].
The SQSTM1 gene encodes sequestosome-1 (also known as the ubiquitin-binding protein p62), which acts as a cargo protein in selective autophagy. In addition to ECH, SQSTM1-ALK has also been reported in some cases of ALK-positive large B-cell lymphoma and lung cancer [12, 17]. In contrast, ALK+ALCL, a kind of T-cell lymphoma, typically involves the NPM1-ALK or TPM3-ALK fusion gene . In Spitz tumors, novel ALK fusions, such as CLIP1-ALK and GTF3C2-ALK, have been discovered . At present, the identification of a fusion gene partner of ALK involves a complicated process, and a combination of H&E staining and immunohistochemistry is needed to make a definitive diagnosis of ALK-positive ECH. Although staining patterns are the same, our case and a previous report showed that 5A4 clone produced stronger staining intensity than ALK1 antibody .
ECH and conventional FH are considered to be benign neoplasms. However, Doyle et al.  reported a rare case of ECH involving multiple lung metastases. The patient died of the disease after wedge resection of the lung metastasis followed by radiotherapy. Doyle et al. did not mention the results of immunohistochemistry , and so it is unclear whether the tumor was ALK-positive. Since other rare cases of FH involving locally aggressive growth or metastasis have been reported , incomplete resection should be avoided.