fbpx
Wikipedia

Epithelioid hemangioendothelioma

January 01, 1970

Epithelioid hemangioendothelioma (EHE) is a rare tumor, first characterized by Sharon Weiss and Franz Enzinger in 1982[1] that both clinically and histologically is intermediate between angiosarcoma and hemangioma. However, a distinct, disease-defining genetic alteration recently described for EHE indicates that it is an entirely separate entity from both angiosarcoma and hemangioma.

Epithelioid Hemangioendothelioma
Micrograph of an epithelioid hemangioendothelioma of the liver.
SpecialtyOncology

EHE is a soft tissue sarcoma and is generally considered a vascular cancer insofar as the ‘lesional’ cells have surface markers typical of endothelial cells (cells lining the interior of blood vessels). EHE was originally described as occurring most commonly in the veins of the extremities (arms and legs) and two organs, the liver[2] and lungs. It has since been described in organs throughout the body. In addition to liver and lungs, bones and skin have been the most frequent organs.

Before the initial description of Weiss, the tumor had been reported under a variety of other names, including histiocytoid hemangioendothelioma, intravascular bronchoalveolar tumor (in the lung), and sclerosing cholangiocarcinoma. In the lung and liver, common sites of metastatic tumor, it was most likely to be confused with carcinoma a far more common type of tumor.

EHE typically occurs in the 20 – 40 age range although the overall age range involved is much broader and a modest predilection for females over males. It often has an indolent course, and many affected people have survived for decades with multi-organ disease.[1]:601 The extent and number of organs involved apparently has little effect on longevity.

Genetics edit

The cytogenetics of EHE gave some of the first clues of an underlying genetic alteration. A balanced, reciprocal translocation t(1;3)(p36.3;q25) in EHE tumor cells was first described by Mendlick et al. in 2001.[3] This led to the landmark paper by Tanas et al. in 2011[4] describing the specific genes involved in the translocation associated with the most common forms of EHE. This alteration results in the fusion of genes coding for two transcription co-activators (transcriptional regulators): TAZ (transcriptional co-activator with PDZ-binding motif) also known as WWTR1 (WW domain-containing transcription regulator protein 1) and CAMTA1 (calmodulin-binding transcription activator 1). The names in parentheses are not relevant to casual (or even science) readers but are included to help distinguish them from other genes. For instance, another gene with an entirely different function, Tafazzin, is unrelated to EHE but confusingly, also referred to as TAZ. In any case, the EHE translocation results in an abnormal ‘fusion gene’ that expresses an abnormal mRNA resulting in synthesis of a fusion protein variant of TAZ that is always turned on. This form of TAZ always resides in the nucleus and therefore is constitutively active. It binds and turns on a very important member of the TEAD family of transcription factors and this causes cells to proliferate. It is this production of the TAZ-TEAD transcriptome that causes the affected endothelial cells to grow into tumors. In normal cells, TAZ is considered a major negative transducer of the Hippo pathway, a signaling system that regulates organ size by causing cells to stop growing when they touch each other (contact inhibition). Many upstream inputs regulate the Hippo signal which normally functions to turn off or de-activate TAZ by keeping it in the cytoplasm and out of the nucleus. In EHE cells, the abnormal fusion TAZ is ‘immune’ to this input and just stays in the nucleus, and continuing to stimulate cell growth.

Note that about 10% of EHE patients harbor a different translocation. This one similarly results in the constitutive activation of YAP, an orthologue of TAZ (i.e., a gene that has sequence and function that are very similar to TAZ). This also results in persistent, unregulated growth of the affected cells and therefore causes EHE-type tumors.

Treatment edit

  • Sirolimus: Also known as rapamycin, this oral medication suppresses the immune system and slows the growth of abnormal lymphatic vessels that form the tumor. This can help shrink EHE tumors and improve symptoms, including pain
  • Tyrosine kinase inhibitors: These drugs, designed as targeted therapies for cancers, have shown short-term success with EHE. Examples include sorafenib, sunitinib and pazopanib.
  • Vincristine: This chemotherapy drug targets all dividing cells within the body and is therefore used to treat many cancers. It is also used for aggressive benign vascular tumors.
  • Interferon: The body produces interferon to combat infections or control inflammation. It has been formulated into a medication that targets blood vessel growth.
  • Multi-agent chemotherapy: EHE tumors that grow rapidly, spread to other tissues or do not respond to other medications may require more aggressive drug therapy. However, this combination of medications is rarely needed in children and young adults with EHE.
  • Others like surgery can be done as treatment for the virus during its most severe.[5]

Prognosis edit

Although Epithelioid Hemangioendothelioma typically presents as a low-grade tumor, occasionally, eHAE presents as high grade and more aggressive. eHAE presenting in the pleura, for example, is associated with a much more aggressive and hard to treat course.[6] There is no standard chemotherapy treatment for eHAE at current but success with drugs such as Interferon, Paclitaxel, MAID combination chemotherapy, Thalidomide and Doxorubicin have been reported.

Epidemiology edit

It is so rare that only 0.01 percent of the cancer population has it and it affects about 1 person in every 1,000,000 worldwide.[7] Around 90 cases are diagnosed in the United States every year.[8] It is unresponsive to any known strain of chemotherapy, making treatment very difficult.

Society edit

There is a Facebook site set up for people with EHE.[9] There is also a Registry for patients to enter their medical history.[10] CRAVAT Center for Research and Analysis of VAscular Tumors is a website for the EHE community.[11] The EHE Rare Cancer Foundation Australia was established in 2015 by Australians with Epithelioid Hemangioendothelioma (EHE).[12] The core objective of the EHE Rare Cancer Foundation Australia is to proactively fundraise in order to support research into this rare cancer in the hope that a maintenance program or cure can be found.[13]

In 2003 photographer and actress Kris Carr was diagnosed with a stable and low grade version of eHAE. Carr has become a success as a 'Wellness Warrior' advocating a vegan lifestyle as a way to avoid and stabilize disease.[14]


See also edit

References edit

  1. ^ Weiss SW, Enzinger FM (September 1982). "Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma". Cancer. 50 (5): 970–81. doi:10.1002/1097-0142(19820901)50:5<970::aid-cncr2820500527>3.0.co;2-z. PMID 7093931.
  2. ^ Mistry AM, Gorden DL, Busler JF, Coogan AC, Kelly BS (December 2012). "Diagnostic and therapeutic challenges in hepatic epithelioid hemangioendothelioma". J Gastrointest Cancer. 43 (4): 521–5. doi:10.1007/s12029-012-9389-y. PMID 22544493. S2CID 23391808.
  3. ^ Mendlick MR, Nelson M, Pickering D, Johansson SL, Seemayer TA, Neff JR, et al. (May 2001). "Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma". Am J Surg Pathol. 25 (5): 684–7. doi:10.1097/00000478-200105000-00019. PMID 11342784. S2CID 26397433.
  4. ^ Tanas MR, Sboner A, Oliveira AM, Erickson-Johnson MR, Hespelt J, Hanwright PJ, et al. (August 2011). "Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma". Sci Transl Med. 3 (98): 98ra82. doi:10.1126/scitranslmed.3002409. PMID 21885404. S2CID 206678129.
  5. ^ "Epithelioid Hemangioendolthelioma (EHE) - Diagnosis & Treatment". Boston Children's Hospital. Retrieved June 17, 2021.
  6. ^ Crotty EJ, McAdams HP, Erasmus JJ, Sporn TA, Roggli VL (December 2000). "Epithelioid hemangioendothelioma of the pleura: clinical and radiologic features". AJR Am J Roentgenol. 175 (6): 1545–9. doi:10.2214/ajr.175.6.1751545. PMID 11090371.
  7. ^ . Boston Children's Hospital. Archived from the original on August 18, 2017.
  8. ^ Paulson, Kelly G.; Ravi, Vinod; Rubin, Brian P.; Park, Min; Loggers, Elizabeth T.; Cranmer, Lee D.; Wagner, Michael J. (2023). "Incidence, demographics, and survival of malignant hemangioendothelioma in the United States". Cancer Medicine. 12 (14): 15101–15106. doi:10.1002/cam4.6181. PMC 10417180. PMID 37260142.
  9. ^ "Epithelioid Hemangioendothelioma (EHE) Cancer". Facebook.
  10. ^ "Home".
  11. ^ "Epithelioid Hemangioendothelioma Cancer Foundation".
  12. ^ generator, metatags. "EHE Rare Cancer Foundation Australia". www.ehefoundation.com.au. Retrieved 2016-07-06.
  13. ^ generator, metatags. "EHE Rare Cancer Foundation Australia". www.ehefoundation.com.au. Retrieved 2016-07-06.
  14. ^ Stein L (July 16, 2008). "Living with Cancer: The Kris Carr's Story". Scientific American.


External links edit

January 01, 1970
epithelioid, hemangioendothelioma, rare, tumor, first, characterized, sharon, weiss, franz, enzinger, 1982, that, both, clinically, histologically, intermediate, between, angiosarcoma, hemangioma, however, distinct, disease, defining, genetic, alteration, rece. Epithelioid hemangioendothelioma EHE is a rare tumor first characterized by Sharon Weiss and Franz Enzinger in 1982 1 that both clinically and histologically is intermediate between angiosarcoma and hemangioma However a distinct disease defining genetic alteration recently described for EHE indicates that it is an entirely separate entity from both angiosarcoma and hemangioma Epithelioid HemangioendotheliomaMicrograph of an epithelioid hemangioendothelioma of the liver SpecialtyOncology EHE is a soft tissue sarcoma and is generally considered a vascular cancer insofar as the lesional cells have surface markers typical of endothelial cells cells lining the interior of blood vessels EHE was originally described as occurring most commonly in the veins of the extremities arms and legs and two organs the liver 2 and lungs It has since been described in organs throughout the body In addition to liver and lungs bones and skin have been the most frequent organs Before the initial description of Weiss the tumor had been reported under a variety of other names including histiocytoid hemangioendothelioma intravascular bronchoalveolar tumor in the lung and sclerosing cholangiocarcinoma In the lung and liver common sites of metastatic tumor it was most likely to be confused with carcinoma a far more common type of tumor EHE typically occurs in the 20 40 age range although the overall age range involved is much broader and a modest predilection for females over males It often has an indolent course and many affected people have survived for decades with multi organ disease 1 601 The extent and number of organs involved apparently has little effect on longevity Contents 1 Genetics 2 Treatment 3 Prognosis 4 Epidemiology 5 Society 6 See also 7 References 8 External linksGenetics editThe cytogenetics of EHE gave some of the first clues of an underlying genetic alteration A balanced reciprocal translocation t 1 3 p36 3 q25 in EHE tumor cells was first described by Mendlick et al in 2001 3 This led to the landmark paper by Tanas et al in 2011 4 describing the specific genes involved in the translocation associated with the most common forms of EHE This alteration results in the fusion of genes coding for two transcription co activators transcriptional regulators TAZ transcriptional co activator with PDZ binding motif also known as WWTR1 WW domain containing transcription regulator protein 1 and CAMTA1 calmodulin binding transcription activator 1 The names in parentheses are not relevant to casual or even science readers but are included to help distinguish them from other genes For instance another gene with an entirely different function Tafazzin is unrelated to EHE but confusingly also referred to as TAZ In any case the EHE translocation results in an abnormal fusion gene that expresses an abnormal mRNA resulting in synthesis of a fusion protein variant of TAZ that is always turned on This form of TAZ always resides in the nucleus and therefore is constitutively active It binds and turns on a very important member of the TEAD family of transcription factors and this causes cells to proliferate It is this production of the TAZ TEAD transcriptome that causes the affected endothelial cells to grow into tumors In normal cells TAZ is considered a major negative transducer of the Hippo pathway a signaling system that regulates organ size by causing cells to stop growing when they touch each other contact inhibition Many upstream inputs regulate the Hippo signal which normally functions to turn off or de activate TAZ by keeping it in the cytoplasm and out of the nucleus In EHE cells the abnormal fusion TAZ is immune to this input and just stays in the nucleus and continuing to stimulate cell growth Note that about 10 of EHE patients harbor a different translocation This one similarly results in the constitutive activation of YAP an orthologue of TAZ i e a gene that has sequence and function that are very similar to TAZ This also results in persistent unregulated growth of the affected cells and therefore causes EHE type tumors Treatment editSirolimus Also known as rapamycin this oral medication suppresses the immune system and slows the growth of abnormal lymphatic vessels that form the tumor This can help shrink EHE tumors and improve symptoms including pain Tyrosine kinase inhibitors These drugs designed as targeted therapies for cancers have shown short term success with EHE Examples include sorafenib sunitinib and pazopanib Vincristine This chemotherapy drug targets all dividing cells within the body and is therefore used to treat many cancers It is also used for aggressive benign vascular tumors Interferon The body produces interferon to combat infections or control inflammation It has been formulated into a medication that targets blood vessel growth Multi agent chemotherapy EHE tumors that grow rapidly spread to other tissues or do not respond to other medications may require more aggressive drug therapy However this combination of medications is rarely needed in children and young adults with EHE Others like surgery can be done as treatment for the virus during its most severe 5 Prognosis editAlthough Epithelioid Hemangioendothelioma typically presents as a low grade tumor occasionally eHAE presents as high grade and more aggressive eHAE presenting in the pleura for example is associated with a much more aggressive and hard to treat course 6 There is no standard chemotherapy treatment for eHAE at current but success with drugs such as Interferon Paclitaxel MAID combination chemotherapy Thalidomide and Doxorubicin have been reported Epidemiology editIt is so rare that only 0 01 percent of the cancer population has it and it affects about 1 person in every 1 000 000 worldwide 7 Around 90 cases are diagnosed in the United States every year 8 It is unresponsive to any known strain of chemotherapy making treatment very difficult Society editThere is a Facebook site set up for people with EHE 9 There is also a Registry for patients to enter their medical history 10 CRAVAT Center for Research and Analysis of VAscular Tumors is a website for the EHE community 11 The EHE Rare Cancer Foundation Australia was established in 2015 by Australians with Epithelioid Hemangioendothelioma EHE 12 The core objective of the EHE Rare Cancer Foundation Australia is to proactively fundraise in order to support research into this rare cancer in the hope that a maintenance program or cure can be found 13 In 2003 photographer and actress Kris Carr was diagnosed with a stable and low grade version of eHAE Carr has become a success as a Wellness Warrior advocating a vegan lifestyle as a way to avoid and stabilize disease 14 See also editList of cutaneous conditions Skin lesionReferences edit Weiss SW Enzinger FM September 1982 Epithelioid hemangioendothelioma a vascular tumor often mistaken for a carcinoma Cancer 50 5 970 81 doi 10 1002 1097 0142 19820901 50 5 lt 970 aid cncr2820500527 gt 3 0 co 2 z PMID 7093931 Mistry AM Gorden DL Busler JF Coogan AC Kelly BS December 2012 Diagnostic and therapeutic challenges in hepatic epithelioid hemangioendothelioma J Gastrointest Cancer 43 4 521 5 doi 10 1007 s12029 012 9389 y PMID 22544493 S2CID 23391808 Mendlick MR Nelson M Pickering D Johansson SL Seemayer TA Neff JR et al May 2001 Translocation t 1 3 p36 3 q25 is a nonrandom aberration in epithelioid hemangioendothelioma Am J Surg Pathol 25 5 684 7 doi 10 1097 00000478 200105000 00019 PMID 11342784 S2CID 26397433 Tanas MR Sboner A Oliveira AM Erickson Johnson MR Hespelt J Hanwright PJ et al August 2011 Identification of a disease defining gene fusion in epithelioid hemangioendothelioma Sci Transl Med 3 98 98ra82 doi 10 1126 scitranslmed 3002409 PMID 21885404 S2CID 206678129 Epithelioid Hemangioendolthelioma EHE Diagnosis amp Treatment Boston Children s Hospital Retrieved June 17 2021 Crotty EJ McAdams HP Erasmus JJ Sporn TA Roggli VL December 2000 Epithelioid hemangioendothelioma of the pleura clinical and radiologic features AJR Am J Roentgenol 175 6 1545 9 doi 10 2214 ajr 175 6 1751545 PMID 11090371 Epithelioid Hemangioendothelioma in children Boston Children s Hospital Archived from the original on August 18 2017 Paulson Kelly G Ravi Vinod Rubin Brian P Park Min Loggers Elizabeth T Cranmer Lee D Wagner Michael J 2023 Incidence demographics and survival of malignant hemangioendothelioma in the United States Cancer Medicine 12 14 15101 15106 doi 10 1002 cam4 6181 PMC 10417180 PMID 37260142 Epithelioid Hemangioendothelioma EHE Cancer Facebook Home Epithelioid Hemangioendothelioma Cancer Foundation generator metatags EHE Rare Cancer Foundation Australia www ehefoundation com au Retrieved 2016 07 06 generator metatags EHE Rare Cancer Foundation Australia www ehefoundation com au Retrieved 2016 07 06 Stein L July 16 2008 Living with Cancer The Kris Carr s Story Scientific American External links edit Retrieved from https en wikipedia org w index php title Epithelioid hemangioendothelioma amp oldid 1191315869, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.