Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD
More than 85 percent of Ewing sarcoma/primitive neuroectodermal tumor, or Ewing family of tumors, have the translocation t(11;22)(q24;q12), while others have variant translocations. Identifying these by cytogenetic or molecular genetic techniques, or both, is specific for Ewing family of tumors (EFT) and is increasingly recognized as the gold standard for diagnosis. However, these techniques are not universally available. The authors, therefore, studied a large group of genetically confirmed EFTs to more completely understand the morphologic and immunophenotypic spectrum of this rare sarcoma. Sixty-six cytogenetically-, FISH-, or RT-PCR-proven EFTs were retrieved. In 56 cases, immunohistochemistry was performed for pancytokeratins (PanCK), high molecular weight cytokeratins (HMWCK), desmin, CD99, CD117, and FLI1 protein using heat-induced epitope retrieval and the Dako Envision system. The cases arose chiefly in children and young adults (median age, 18 years; range, three to 65 years) of both genders (male, 32; female, 31; unknown, three) in a variety of bone (n=9) and soft tissue (n=27) sites. Histologically, 46 cases showed only typical features of Ewing sarcoma, nine cases showed features of primitive neuroectodermal tumor, three cases showed adamantinoma-like features, three cases corresponded to atypical Ewing sarcoma, three cases showed principally intersecting fascicles of spindled cells, and two cases had abundant hyalinized matrix. Immunohistochemistry results were as follows: PanCK (18 of 56; 32 percent), HMWCK (three of 55; five percent), desmin (one of 56; two percent), CD99 (52 of 52; 100 percent), CD117 (13 of 54; 24 percent), and FLI1 (44 of 47; 94 percent). HMWCK was expressed only in adamantinoma-like EFTs, none of which expressed desmin. The authors concluded that most, but not all, EFTs can be diagnosed using time-honored morphologic criteria and ancillary immunohistochemistry. However, genetic confirmation remains essential for the diagnosis of unusual morphologic variants of EFT, including adamantinoma-like, spindled, sclerosing, and clear cell/anaplastic variants. Therefore, one must use cytogenetics or molecular analysis to exclude or confirm the diagnosis of Ewing sarcoma in round cell sarcomas having a variety of patterns but not specifically conforming to a tumor of known lineage—for example, rhabdomyosarcoma.
Folpe AL, Goldblum JR, Rubin BP, et al. Morphologic and immunophenotypic
diversity in Ewing family tumors: a study of 66 genetically confirmed
J Surg Pathol. 2005;29:1025-1033.
Reprints: Dr. Andrew L. Folpe, Dept. of Pathology, H-175, Emory University
Hospital, 1364 Clifton Rd. NE, Atlanta, GA 30322; email@example.com
Differentiating pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma is difficult, especially in biopsy specimens from head and neck mucosa. The problem is compounded by inflamed and often poorly oriented tissue sections. The authors attempted to distinguish pseudoepitheliomatous hyperplasia from invasive squamous cell carcinoma using a panel of antibodies to various epithelial and stromal elements (p53, matrix metalloproteinase 1, E-cadherin, and collagen IV) that has been shown to be useful in differentiating intestinal adenomas with invasive adenocarcinoma from displaced adenomatous epithelium. They immunostained and examined 33 archival specimens (16 squamous cell carcinoma [12 with invasion and four with microinvasion] and 17 pseudoepitheliomatous hyperplasia) from head and neck mucosal locations and found increased nuclear staining of the invasive tumor cells with p53. They also noted decreased staining within invasive tumor nests with E-cadherin, and highly significant increased staining within tumor cells and adjacent stroma with matrix metalloproteinase 1 (P<.001). The only antibody in the panel that did not show a reliable staining pattern was collagen IV, which appeared fragmented in benign inflamed and malignant areas and therefore was not useful. The authors concluded that p53, matrix metalloproteinase 1, and E-cadherin showed significant staining trends independent of inflammation and suboptimal tissue orientation. Although a properly oriented hematoxylin-and-eosin-stained section was their gold standard, they found this immunoperoxidase panel useful as a diagnostic adjunct in difficult cases.
Zarovnaya E, Black C. Distinguishing pseudoepitheliomatous hyperplasia
from squamous cell carcinoma in mucosal biopsy specimens from the head
and neck. Arch
Pathol Lab Med. 2005;129:1032-1036.
Reprints: Dr. Candice Black, Dept. of Pathology, Dartmouth-Hitchcock Medical
Center, 1 Medical Center Drive, Lebanon, NH 03756; firstname.lastname@example.org
Surgical pathologists often encounter hydropic villi in products of conception at the first trimester and must determine whether the villi represent complete hydatidiform mole (CM), partial hydatidiform mole (PM), or hydropic abortion (HA). Distinguishing between these is important for determining appropriate patient treatment. This study assessed interobserver and intraobserver variability in the histologic diagnosis of hydatidiform mole among five placental pathologists. To evaluate interobserver variability, one representative slide from each of 50 mixed cases of PM, CM, and HA of the first trimester was circulated among the pathologists. All of the pathologists used the same histologic criteria by Szulman and Surti. For the second round, the same cases were submitted with DNA ploidy data. For the third round, the slides were recoded and distributed to assess intraobserver agreement. Kappa value was calculated for interobserver agreement in the first and second rounds. There was agreement among four or five pathologists for only 30 of 50 cases in the first round. The pathologists had problems differentiating between PM and HA in most of the remaining 20 cases. The κ values varied from poor (κ=0.104) to excellent (κ=0.761) in the first round. In the second round, there was agreement in 39 of 50 cases, and the level of agreement increased remarkably, ranging from fair to good (κ=0.552) to excellent (κ=0.851). The number of discrepant cases, PM versus HA, was reduced to four. In seven cases, the pathologists had difficulty distinguishing CM from HA. The intraobserver agreement ranged from 50 percent to 90 percent. Poor interobserver agreement was demonstrated when histology alone was used for diagnosis. Discordance was most frequently seen in PM versus HA and resulted from difficulty in evaluating trophoblastic hyperplasia. Polar trophoblastic growth seen in HA could also be observed in PM. Adding ploidy data significantly improved concordance. The authors noted that significant interobserver and intraobserver variability was observed even among placental pathologists. They concluded that new histologic criteria that can be adapted to the differentiation of early lesions are needed.
Fukunaga M, Katabuchi H, Nagasaki T, et al. Interobserver and intraobserver
variability in the diagnosis of hydatidiform mole. Am
J Surg Pathol. 2005;29:942-947.
Reprints: Dr. Masaharu Fukunaga, Dept. of Pathology, Jikei Daisan Hospital,
4-11-1, Izumihoncho, Komaeshi, Tokyo, 201-8601, Japan; email@example.com
Dr. Cibull is professor of pathology and laboratory medicine and direct
of surgical pathology, University of Kentucky Medical Center, Lexington.
Dr. Lele is assistant professor of pathology and laboratory medicine, University
of Kentucky Medical Center. Dr. Kesler is hematopathology fellow, University
of Texas Southwestern Medical Center at Dallas.