ABSTRACT
Previous studies showed that ALK is often positive in epithelioid fibrous histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded. Our objective was to study a series of EFH to present histopathological variations of EFH, identify novel ALK gene fusions, and determine whether there is a correlation between histopathological features and particular gene. We investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed histopathologically as well as for ALK and TFE-3 rearrangements using FISH and ALK gene fusions using next-generation sequencing. The analysis of the sequencing results was performed using the Archer Analysis software (v5; ArcherDX Inc). The study group consisted of 8 female and 6 male patients, ranging in age from 18 to 79 years (mean 42 years; median 37.5 years). All presented with a solitary lesion. Microscopically, most lesions were polypoid and composed of epithelioid cells with ample cytoplasm. In addition, a variable number of bi-, tri-, or multinucleated, spindled, multilobated, cells with eccentric nuclei, cells with nuclear pseudoinclusions, mucinous, and grooved cells were admixed. In 5 cases, the predominant epithelioid cell component consisted of rather small cells, whereas spindled cells dominated in 3 cases. Of these, 2 lesions were composed rather of pale eosinophilic to clear cells, occasioning a resemblance to PEComa or leiomyoma. Immunohistochemically, all cases expressed ALK and 11 were positive for TFE-3. The break apart test for ALK was positive in 11 cases, whereas specimens from the remaining 3 cases were not analyzable. ALK genes fusions were found in all but 3 cases and included SQSTM1-ALK (3), VCL-ALK (3), TMP3-ALK (2), PRKAR2A-ALK (1), MLPH-ALK (1), and EML4-ALK (1). No correlation between histological features and type of ALK fusion was found. TFE-3 break apart test was negative. It is concluded that ALK-immunopositive EFH shows ALK gene fusions that involve various protein-coding genes, implicated in a variety of biological processes. Rare variants of EFH rather consist of spindled "non-epithelioid" cells.
Subject(s)
Anaplastic Lymphoma Kinase/genetics , Histiocytoma, Benign Fibrous/genetics , Histiocytoma, Benign Fibrous/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Female , Gene Rearrangement , Humans , Male , Middle Aged , Oncogene Fusion , Young AdultABSTRACT
The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.
