Clonal X Chromosome Inactivation Suggests That Splenic Cord Capillary Hemangioma and Myoid Angioendothelioma Are True Neoplasms and Not Subtypes of Splenic Hamartoma
A Chiu, M Czader, L Cheng, M Wang, DM Knowles, H Al-Ahmadie, A Orazi. Weill Cornell Medical College, New York, NY; Indiana University, Indianapolis, IN; The University of Chicago, Chicago, IL
Background: Splenic hamartoma (SH) is a rare tumor-like proliferation composed of structurally disorganized red pulp elements. It has been hypothesized that other red pulp lesions, such as cord capillary hemangioma (CCH) and myoid angioendothelioma (MA), may fall within the spectrum of SH, simply representing morphological variants. We utilized immunohistology and histochemistry to compare the vascular and stromal composition of classical SH (C-SH) with cases of CCH and MA. In addition, we ascertained their clonal vs. polyclonal nature.
Design: Paraffin sections from 11 cases (6, CCH; 3, MA; 2, C-SH) were assessed by reticulin and trichrome stains and immunohistology for stromal (Collagen IV,SMA,NGFR), vascular (CD34,CD31,CD8,D2-40), histiocytic (CD163), and proliferation (MIB-1) markers, and EBV-RNA (EBER). Clonality by HUMARA assay was performed in 7 female cases by laser-assisted microdissection (PixCell II System, Arcturus Engineering, Mountain View, CA), sampling areas of hamartoma and normal spleen. Samples with/without HhaI restriction endonuclease digestion were analyzed by PCR on polyacrylamide gels by autoradiography. The samples were informative if the control samples displayed two alleles without HhaI digestion. Nonrandom inactivation of the X chromosomes was defined as a complete or near complete absence of one or the other allele after HhaI digestion, indicating predominance of one X-linked human androgen receptor allele.
Results: All cases showed increased reticulin and collagen content. The 2 C-SH cases showed a CD8(+) vasculature, while CCH and MA cases contained many CD34(+) CD31(+) vessels but little CD8(+) vasculature. All cases were D2-40(-), EBV(-), and had <10% MIB-1. CCH and MA cases lacked perisinusoidal expression of collagen IV or NGFR. Increased CD163(+) histiocytes were found in 2 cases (1 MA; 1 CCH). Nonrandom X-chromosome inactivation was informative in all 7 cases. Three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All clonal cases had non-classical SH morphology.
Conclusions: In spite of considerable morphologic heterogeneity and overlapping features, C-SH and non-classical SH lesions termed CCH and MA are different in terms of vascular/stromal composition. Clonality analysis supports a true neoplastic origin for the two latter diseases.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 139, Tuesday Morning