(CANCER RESEARCH 52, 6224-6228. November 15. 1992] Clonal Rearrangement of Chromosome Band 6p21 in the Mesenchymal Component of Pulmonary Chondroid Hamartoma1 Jonathan A. Fletcher,2 Geraldine S. Pinkus, Kevin Donovan, Rizwan Naeem, David J. Sugarbaker, Steven Mentzer, Jack L. Pinkus, and Janina Longtine Department of Pathology [J. A. F., G. S. P.. K. D., R. N., J. L. P., J. L.] and Division of Thoracic Surgery ¡D.J. S., S. M. J, Brigham and Women's Hospital; the Division of Pediatrie-Oncologi; Dana-Farber Cancer Institute [J. A. F. J; the Division of Hematology-Oncology, Children's Hospital fj. A. F. J; and the Departments of Pathology, Surgery, and Pediatrics, Harvard Medical School, Boston, Massachusetts 02115 ABSTRACT Pulmonary chondroid hamartomas (PCH) are biphasic benign tu mors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromo some band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14Xp21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberra tions are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated. INTRODUCTION PCH3 are unusual benign tumors that occur in both children and adults. PCH are generally asymptomatic nodules that arise in the periphery of the lungs, and most cases are discovered incidentally during routine radiographie studies or at postmor tem examination (1,2). Most PCH are composed of epithelial- lined clefts that are situated within a heterogeneous prolifera tion of mesenchymal cells. The mesenchymal population in a given PCH might include fibrous connective tissue, fat, and mature and/or immature chondroid tissue. Although PCH were thought originally to represent hyperplastic developmental remnants, it has been suggested that the epithelial and mesen chymal components, or the mesenchymal component alone, might be neoplastic (1-4). Malignant transformation in PCH is exceptionally rare, however, and cure is accomplished invari ably by surgical resection (5). We have described clonal chromosome rearrangements in the mesenchymal components of two PCH (6). One of those tu mors contained a balanced translocation (6;14)(p21;q24) and a chromosome 11 long arm deletion, whereas the other contained clonal rearrangements of chromosomes 12 and 18. Herein, we report two additional cases of PCH in which clonal rearrange ment at chromosome band 6p21 was demonstrated in mesen chymal cells. MATERIALS AND METHODS Case Reports Case 1. A 37-year-old woman underwent wedge resection of an as ymptomatic right lower lobe PCH that was 0.8 cm in its greatest di ameter. 11istologi-ali). the PCH was composed of varied mesenchymal Received 4/29/92; accepted 9/10/92. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accord ance with 18 U.S.C. Section 1734 solely to indicate this fact. 1This study was supported in part by a Physician-Scientist Award <lKHCAOI498-02)to J. A. F. from the NIH. 2 To whom requests for reprints should be addressed, at Department of Pathol ogy. Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. 3The abbreviations used are: PCH, pulmonary chondroid hamartomas; APAAP, alkaline phosphatase anti-alkaline phosphatase. cell types along with lumina lined by benign columnar or cuboidal epithelium (Fig. 1). The mesenchymal components included immature cells within a myxoid stroma (65% of the total mesenchyme), mature adipose tissue (20% of the total mesenchyme), and mature cartilage ( 15% of the total mesenchyme). Case 2. A 68-year-old man underwent wedge resection of an asymp tomatic left lower lobe PCH that was 2. 5 cm in greatest diameter. Histologically, the PCH was composed predominantly of mesenchymal cell populations that included immature cells in a loose, myxoid stroma (80%), scattered foci of adipose tissue (15%), and a minor component of mature cartilage (5%). The PCH also contained scattered lumina, lined by cuboidal or columnar epithelium, that in some cases were associated with chronic inflammatory cells. The epithelial cells were noted primarily at the periphery of the hamartoma. Cytogenetic and in Situ Hybridization Analyses Sterile specimens of each PCH were obtained directly from the fro zen section room and were disaggregated, cultured, and karyotyped using methods described previously (6). Metaphase cells were harvested after 5-6 days in culture. Chromosome abnormalities were described using the conventions proposed in the International System for Human Cytogenetic Nomenclature (1991) (7). Fluorescent in situ hybridization studies were carried out with a spectrum orange-labeled probe cocktail to chromosome 6 (Imagenetics, Naperville, IL) and a biotinylated probe cocktail to chromosome 14 (Oncor, Gaithersburg, MD), according to the manufacturers' protocols. Immunohistochemical/Cytogenetic Analyses Combined immunohistochemical/cytogenetic analyses were carried out on fresh metaphase cell preparations as described previously (6). The immunohistochemical/cytogenetic analyses used APAAP imnui- nohistochemical staining to determine tissue lineages of quinacrine- banded metaphase cells. Mesenchymal and epithelial cell lineages were established using mouse monoclonal antibodies to vimentin (Dako Corp., Carpenteria, CA) and keratin proteins (AE1/AE3; Boehringer Mannheim, Indianapolis. IN), respectively. Incubations with the pri mary antibodies were followed by incubations with rabbit anti-mouse immunoglobulin antibodies and APAAP complexes (Dako). APAAP complexes were detected using naphthol AS-MX phosphate (Sigma Chemical Co., St. Louis, MO) as substrate and Fast Red TR salt (Sigma) as chromagen. RESULTS Cytogenetic Analyses Case 1. Phase microscopy at the time of metaphase cell harvests revealed spindled (mesenchymal) and epithelial mor phologies in 80 and 20%, respectively, of cultured cells. Twenty metaphase cells were analyzed after trypsin-Giemsa banding. Thirteen cells were pseudodiploid: 46,XX,der(6)t(6;14)(p21;q24)- ?ins(6;/-/)(p21 ;q22q23),t(7; 15)(q22;q22),der( 14)t(6; 14)(p21 ;q24) (Fig. 2), and the remaining seven cells were diploid: 46,XX. The translocation break points in the t(6;14) were identical to those in a PCH that we reported previously (Ref. 6, case 2). However, 6224 Research. on January 7, 2016. © 1992 American Association for Cancer cancerres.aacrjournals.org Downloaded from