Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma

A. Chiu, M. Czader, L. Cheng, R. P. Hasserjian, M. Wang, S. Bhagavathi, E. M. Hyjek, H. Al-Ahmadie, D. M. Knowles, A. Orazi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8 CD31 CD34 splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8 CD31 CD34 cord capillaries, but very little CD8 vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of 5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings.

Original languageEnglish (US)
Pages (from-to)108-116
Number of pages9
JournalModern Pathology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Capillary Hemangioma
X Chromosome Inactivation
Hamartoma
Hemangioendothelioma
Neoplasms
Blood Vessels
Collagen
Reticulin
Nerve Growth Factor Receptor
Histiocytes
Human Herpesvirus 4
Lasers
RNA

Keywords

  • clonality
  • cord capillary hemangioma
  • hamartoma
  • myoid angioendothelioma
  • sclerosing angiomatoid nodular transformation
  • spleen

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma. / Chiu, A.; Czader, M.; Cheng, L.; Hasserjian, R. P.; Wang, M.; Bhagavathi, S.; Hyjek, E. M.; Al-Ahmadie, H.; Knowles, D. M.; Orazi, A.

In: Modern Pathology, Vol. 24, No. 1, 01.01.2011, p. 108-116.

Research output: Contribution to journalArticle

Chiu, A. ; Czader, M. ; Cheng, L. ; Hasserjian, R. P. ; Wang, M. ; Bhagavathi, S. ; Hyjek, E. M. ; Al-Ahmadie, H. ; Knowles, D. M. ; Orazi, A. / Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma. In: Modern Pathology. 2011 ; Vol. 24, No. 1. pp. 108-116.
@article{14938ea1908d4ad0912d5c0a70bc63da,
title = "Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma",
abstract = "Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8 CD31 CD34 splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8 CD31 CD34 cord capillaries, but very little CD8 vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of 5{\%} by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings.",
keywords = "clonality, cord capillary hemangioma, hamartoma, myoid angioendothelioma, sclerosing angiomatoid nodular transformation, spleen",
author = "A. Chiu and M. Czader and L. Cheng and Hasserjian, {R. P.} and M. Wang and S. Bhagavathi and Hyjek, {E. M.} and H. Al-Ahmadie and Knowles, {D. M.} and A. Orazi",
year = "2011",
month = "1",
day = "1",
doi = "10.1038/modpathol.2010.168",
language = "English (US)",
volume = "24",
pages = "108--116",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma

AU - Chiu, A.

AU - Czader, M.

AU - Cheng, L.

AU - Hasserjian, R. P.

AU - Wang, M.

AU - Bhagavathi, S.

AU - Hyjek, E. M.

AU - Al-Ahmadie, H.

AU - Knowles, D. M.

AU - Orazi, A.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8 CD31 CD34 splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8 CD31 CD34 cord capillaries, but very little CD8 vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of 5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings.

AB - Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8 CD31 CD34 splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8 CD31 CD34 cord capillaries, but very little CD8 vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of 5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings.

KW - clonality

KW - cord capillary hemangioma

KW - hamartoma

KW - myoid angioendothelioma

KW - sclerosing angiomatoid nodular transformation

KW - spleen

UR - http://www.scopus.com/inward/record.url?scp=78650913476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650913476&partnerID=8YFLogxK

U2 - 10.1038/modpathol.2010.168

DO - 10.1038/modpathol.2010.168

M3 - Article

C2 - 20852592

AN - SCOPUS:78650913476

VL - 24

SP - 108

EP - 116

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

IS - 1

ER -