Granulocytic sarcoma: Difference between revisions
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==Classification== | ==Classification== | ||
* GS can be classified into two categories based on its co-occurence with other malignancies: | |||
* GS associated with other myeloid diseases: | |||
** Acute leukemias (especially AML) | |||
** Myelodysplastic syndromes | |||
** Other myeloproliferative diseases | |||
*Isolated GS | |||
==Pathophysiology== | ==Pathophysiology== | ||
* Infiltration of the tumor with myeloblasts is the main characteristic of the tumor on H&E stain. | * Infiltration of the tumor with myeloblasts is the main characteristic of the tumor on H&E stain. | ||
Line 30: | Line 30: | ||
==Differentiating GS from other Diseases== | ==Differentiating GS from other Diseases== | ||
*GS must be differentiated from other diseases that can present as extramedullary solid tumors, such as: | *GS must be differentiated from other diseases that can present as extramedullary solid tumors, such as: | ||
* Large cell lymphoma | |||
* Non-Hodgkin lymphoma | |||
* Thymoma | |||
* Myeloma | |||
* Esosinophilic sarcoma | |||
* Ewing sarcoma | |||
* Extramedullary sites of hematopoiesis | |||
* Burkitt lymphoma | |||
* Hypereosinophilic syndrome | |||
* Polycythemia vera | |||
All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies. | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Line 52: | Line 52: | ||
===Gender=== | ===Gender=== | ||
*GS affects both men and women. | * GS affects both men and women. | ||
* Due to the rarity of the disease it is not clear whether there is a gender predilection for it. | |||
*Due to the rarity of the disease it is not clear whether there is a gender predilection for it. | |||
===Race=== | ===Race=== | ||
*There is no racial predilection for GS. | * There is no racial predilection for GS. | ||
==Risk Factors== | ==Risk Factors== | ||
*Risk factors for GS are usually chromosomal aberrations and include<ref name=":0">{{Cite journal|last=Daniela Dörfel et al.|first=|date=2016|title=Cardiac Myeloid Sarcoma: Multimodality Radiologic Imaging Features and Pathologic Correlation|url=https://www.amjmed.com/article/S0002-9343(16)30356-4/fulltext|journal=The American Journal of Medicine|volume=129|pages=e117-e120|via=}}</ref>: | * Risk factors for GS are usually chromosomal aberrations and include<ref name=":0">{{Cite journal|last=Daniela Dörfel et al.|first=|date=2016|title=Cardiac Myeloid Sarcoma: Multimodality Radiologic Imaging Features and Pathologic Correlation|url=https://www.amjmed.com/article/S0002-9343(16)30356-4/fulltext|journal=The American Journal of Medicine|volume=129|pages=e117-e120|via=}}</ref>: | ||
**Trisomy 8 | ** Trisomy 8 | ||
**Monosomy 7 | ** Monosomy 7 | ||
**MLL gene rearrangement | ** MLL gene rearrangement | ||
**NPM1 mutations | ** NPM1 mutations | ||
**FLT3 mutations | ** FLT3 mutations | ||
== Natural History, Complications and Prognosis== | == Natural History, Complications and Prognosis== | ||
*How GS evolves over time depends on the co-occurence of the disease with other malignancies. | * How GS evolves over time depends on the co-occurence of the disease with other malignancies. | ||
*GS may present before evidences of other malignancies manifest or after these malignancies are evident. | * GS may present before evidences of other malignancies manifest or after these malignancies are evident. | ||
*Symptoms of the isolated GS depends on the location and the site of the tumor. | * Symptoms of the isolated GS depends on the location and the site of the tumor. | ||
*Majority of cases are associated with AML or other myeloproliferative/myelodysplastic syndromes. | * Majority of cases are associated with AML or other myeloproliferative/myelodysplastic syndromes. | ||
*Majority of GS tumors are found in the soft tissues such as the peritoneum, lymph nodes, CNS and skin. They are also found in bone and periosteum. | * Majority of GS tumors are found in the soft tissues such as the peritoneum, lymph nodes, CNS and skin. They are also found in bone and periosteum. | ||
*Early clinical features include weight loss, weakness. Other manifestations of the tumor depend on its size and location. | * Early clinical features include weight loss, weakness. Other manifestations of the tumor depend on its size and location. | ||
*Prognosis of GS depends on its association with other malignacies. In cases of isolated GS the prognosis is good. However, GS associated with myeloproliferative disorders has poor prognosis. | * Prognosis of GS depends on its association with other malignacies. In cases of isolated GS the prognosis is good. However, GS associated with myeloproliferative disorders has poor prognosis. | ||
*Prognosis of isolated GS with chromosome 8 abnormalities is worse than other cases of isolated GS. | * Prognosis of isolated GS with chromosome 8 abnormalities is worse than other cases of isolated GS. | ||
== Diagnosis == | == Diagnosis == | ||
===Diagnostic Criteria=== | ===Diagnostic Criteria=== | ||
*There are no predefined criteria for diagnosis of granulocytic sarcoma. | * There are no predefined criteria for diagnosis of granulocytic sarcoma. | ||
*Granulocytic sarcoma must be suspected in patients with AML or myelodysplatic syndromes. Diagnosis must be confirmed with histopathologic study of the specimen. | * Granulocytic sarcoma must be suspected in patients with AML or myelodysplatic syndromes. Diagnosis must be confirmed with histopathologic study of the specimen. | ||
=== Symptoms === | === Symptoms === | ||
*Symptoms of GS may include the following: | * Symptoms of GS may include the following: | ||
* Symptoms due to mass effect such as deafness, ptosis, altered vision, intestinal obstruction, etc. | |||
* Headache, neck pain, abdominal pain,etc. based on the site of the tumor | |||
* Constitutional symptoms such as fever, fatigue, etc. | |||
=== Physical Examination === | === Physical Examination === | ||
*Patients with GS can present with varying presentations. | * Patients with GS can present with varying presentations. | ||
*Physical examination may be remarkable for: | * Physical examination may be remarkable for: | ||
* Lymph node enlargement (in cases associated with AML and other myeloproliferative syndromes) | |||
* Skin lesions (of varying colors such as green, grey, brown, etc.) | |||
* Organ enlargement such as hepatosplenomegaly. | |||
* Petechiae in patients with thrombocytopenia | |||
* Hearing loss | |||
* Heart murmurs in cases with heart chamber masses | |||
* Crackles on lung auscultation | |||
* Abdominal distention/tenderness in cases with intestinal obstruction | |||
* Limb swelling due to different pathologies such as deep vein thrombosis (DVT). | |||
=== Laboratory Findings === | === Laboratory Findings === | ||
*In cases associated with AML/CML anemia, thrombocytopenia with normal, low or high white blood cells can be present. | * In cases associated with AML/CML anemia, thrombocytopenia with normal, low or high white blood cells can be present. | ||
*In cases associated with polycythemia vera, thrombocytosis and high levels of hemoglobin is present in complete blood count (CBC). | * In cases associated with polycythemia vera, thrombocytosis and high levels of hemoglobin is present in complete blood count (CBC). | ||
*High eosinophil levels can be present in CBC. | * High eosinophil levels can be present in CBC. | ||
===Imaging Findings=== | ===Imaging Findings=== | ||
*In cases of CNS involvement, magnetic resonance imaging (MRI) or CT scan of the CNS can reveal extra-axial masses. | * In cases of CNS involvement, magnetic resonance imaging (MRI) or CT scan of the CNS can reveal extra-axial masses. | ||
*In cases with soft tissue involvement, sonogram of the tissue can reveal the mass. | * In cases with soft tissue involvement, sonogram of the tissue can reveal the mass. | ||
*GS appears as<ref>{{Cite journal|last=Guermazi et al.|first=|date=2002|title=Granulocytic sarcoma (chloroma): imaging findings in adults and children|url=https://www.ajronline.org/doi/full/10.2214/ajr.178.2.1780319|journal=American Journal of Roentgenology|volume=178|pages=319-25|via=}}</ref>: | * GS appears as<ref>{{Cite journal|last=Guermazi et al.|first=|date=2002|title=Granulocytic sarcoma (chloroma): imaging findings in adults and children|url=https://www.ajronline.org/doi/full/10.2214/ajr.178.2.1780319|journal=American Journal of Roentgenology|volume=178|pages=319-25|via=}}</ref>: | ||
* Hyperdense/isodence to brain/muscle in CT scan without enhancement | |||
* Isointense/hyperintense on T2-weighted MRI | |||
* Isointemse/hypointense on T1-weighted MRI | |||
[[File:Chloroma histopathology micrograph (H&E stain).jpeg|thumb|Histopathologic micrograph of GS. Infiltration with myeloblasts which can be seen in the course of AML. Courtesy of image: Wikipedia (By Nephron - Own work, CC BY-SA 3.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=15893726</nowiki>)]] | [[File:Chloroma histopathology micrograph (H&E stain).jpeg|thumb|Histopathologic micrograph of GS. Infiltration with myeloblasts which can be seen in the course of AML. Courtesy of image: Wikipedia (By Nephron - Own work, CC BY-SA 3.0, <nowiki>https://commons.wikimedia.org/w/index.php?curid=15893726</nowiki>)]] | ||
*Abdominal plain radiogram can reveal obstruction, intussusception, etc. | * Abdominal plain radiogram can reveal obstruction, intussusception, etc. | ||
*Echocardiogram may reveal mobile masses in any heart chamber in cases of heart involvement. | * Echocardiogram may reveal mobile masses in any heart chamber in cases of heart involvement. | ||
*Chest radiographs can show lymph node enlargement and consolidation. | * Chest radiographs can show lymph node enlargement and consolidation. | ||
=== Other Diagnostic Studies === | === Other Diagnostic Studies === | ||
*Peripheral blood smear can reveal circulating blasts. | * Peripheral blood smear can reveal circulating blasts. | ||
*Flow cytometry can help differentiate AML from acute lymphoblastic leukemia (ALL). | * Flow cytometry can help differentiate AML from acute lymphoblastic leukemia (ALL). | ||
*Histopathologic analysis of biopsy specimen retrieved by excision or fine needle aspiration shows abundant myeloblasts. | * Histopathologic analysis of biopsy specimen retrieved by excision or fine needle aspiration shows abundant myeloblasts. | ||
*Histopathologic analysis of GS lesions reveals high infiltration with myeloblasts. | * Histopathologic analysis of GS lesions reveals high infiltration with myeloblasts. | ||
== Treatment == | == Treatment == | ||
=== Medical Therapy === | === Medical Therapy === | ||
*Chemotherapy is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis. | * Chemotherapy is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis. | ||
*Patients receiving cytarabine have better prognosis<ref name=":0" />. | * Patients receiving cytarabine have better prognosis<ref name=":0" />. | ||
*Patients with chemotherpeutic regimens accepted for AML had longer period of progression to AML. | * Patients with chemotherpeutic regimens accepted for AML had longer period of progression to AML. | ||
*Treatment includes different regimens<ref>{{Cite journal|last=Yilmaz, A. F., Saydam, G., Sahin, F., & Baran, Y.|first=|date=2013|title=Granulocytic sarcoma: a systematic review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875275/|journal=American Journal of Blood Research|volume=|pages=|via=}}</ref>: | * Treatment includes different regimens<ref>{{Cite journal|last=Yilmaz, A. F., Saydam, G., Sahin, F., & Baran, Y.|first=|date=2013|title=Granulocytic sarcoma: a systematic review|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875275/|journal=American Journal of Blood Research|volume=|pages=|via=}}</ref>: | ||
* Idarubicine and cytarabine | |||
* Fludarabine and cytarabine | |||
* Idarubicine and G-CSF | |||
* Cyclophosphamide, cytarabine, topotecan and G-CSF | |||
*All of these therapeutic agents act through DNA damage and interferes with DNA synthesis. | *All of these therapeutic agents act through DNA damage and interferes with DNA synthesis. | ||
===Bone marrow transplantation=== | ===Bone marrow transplantation=== | ||
*Hematopoietic stemm cell transplantation can be considered as a treatment option following induction chemotherapy in patients with AML<ref name=":1">{{Cite journal|last=Richard L. Bakst, Martin S. Tallman, Dan Douer and Joachim Yahalom|first=|date=2011|title=How I treat extramedullary acute myeloid leukemia|url=http://www.bloodjournal.org/content/118/14/3785?sso-checked=true|journal=Blood|volume=118|pages=3785-3793|via=}}</ref>. | * Hematopoietic stemm cell transplantation can be considered as a treatment option following induction chemotherapy in patients with AML<ref name=":1">{{Cite journal|last=Richard L. Bakst, Martin S. Tallman, Dan Douer and Joachim Yahalom|first=|date=2011|title=How I treat extramedullary acute myeloid leukemia|url=http://www.bloodjournal.org/content/118/14/3785?sso-checked=true|journal=Blood|volume=118|pages=3785-3793|via=}}</ref>. | ||
===Radiation=== | ===Radiation=== | ||
*Radiation can be considered as an adjunctive therapy<ref name=":1" />. | * Radiation can be considered as an adjunctive therapy<ref name=":1" />. | ||
*Combination of chemotherapy and radiotherapy can be considered in patients with CNS involvement or when rapid regression of symptoms is required. | * Combination of chemotherapy and radiotherapy can be considered in patients with CNS involvement or when rapid regression of symptoms is required. | ||
=== Surgery === | === Surgery === | ||
*Surgery alone is not a good treatment strategy for GS. | * Surgery alone is not a good treatment strategy for GS. | ||
*Surgery can be considered prior to chemotherapy in patients where debulking can better the prognosis and help with symptom relief<ref>{{Cite journal|last=Antic D et al.|first=|date=2013|title=Is there a "gold" standard treatment for patients with isolated myeloid sarcoma?|url=https://www.sciencedirect.com/science/article/abs/pii/S0753332212001060?via%3Dihub|journal=Biomed Pharmacother|volume=67|pages=72-77|via=}}</ref>. | * Surgery can be considered prior to chemotherapy in patients where debulking can better the prognosis and help with symptom relief<ref>{{Cite journal|last=Antic D et al.|first=|date=2013|title=Is there a "gold" standard treatment for patients with isolated myeloid sarcoma?|url=https://www.sciencedirect.com/science/article/abs/pii/S0753332212001060?via%3Dihub|journal=Biomed Pharmacother|volume=67|pages=72-77|via=}}</ref>. | ||
*Surgery can also have a diagnostic role in cases where excision of the mass provides specimen for histopatjologic diagnosis. | * Surgery can also have a diagnostic role in cases where excision of the mass provides specimen for histopatjologic diagnosis. | ||
=== Prevention === | === Prevention === | ||
*There are no primary preventive measures available for GS. | * There are no primary preventive measures available for GS. | ||
==References== | ==References== |
Revision as of 19:58, 14 May 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Historical Perspective
- Granulocytic sarcoma (GS, also known as chloroma) was first discovered by Allen Burns, a British physician, in 1811 [1].
- The term chloroma was first used by King to address the greenish appearance of the tumor due to myeloperoxidase.
- The association of the GS with acute myeloid leukemia (AML) was first recognized bt Dock in 1902 [2].
- The term "granulocytic sarcoma" was suggested by Rappaport in 1967 to grant generalisability to it [3].
Classification
- GS can be classified into two categories based on its co-occurence with other malignancies:
- GS associated with other myeloid diseases:
- Acute leukemias (especially AML)
- Myelodysplastic syndromes
- Other myeloproliferative diseases
- Isolated GS
Pathophysiology
- Infiltration of the tumor with myeloblasts is the main characteristic of the tumor on H&E stain.
- GS rises from primitive precursors of granulocytes.
- The disease is an extramedullary manifestation of myeloid diseases, however, it can occur as a primary disease.
- Aggregation of myeloblasts, promyelocytes and myelocytes outside of the bone marrow presents itself as these solid tumors.
- Tumors can occur at any site and can appear as green, gray, white or brown masses.
Clinical Features
Differentiating GS from other Diseases
- GS must be differentiated from other diseases that can present as extramedullary solid tumors, such as:
- Large cell lymphoma
- Non-Hodgkin lymphoma
- Thymoma
- Myeloma
- Esosinophilic sarcoma
- Ewing sarcoma
- Extramedullary sites of hematopoiesis
- Burkitt lymphoma
- Hypereosinophilic syndrome
- Polycythemia vera
All patients with GS must be evaluated for concurrent or future malignancies as GS can occur in the course of or prior to other malignancies.
Epidemiology and Demographics
- The prevalence of GS is approximately 2 per 1,000,000 individuals worldwide.
- Most of the cases of GS are case reports and the disease is extremely rare.
Age
- Patients of all age groups may develop GS.
- GS associated with AML occurs more commonly in children.
Gender
- GS affects both men and women.
- Due to the rarity of the disease it is not clear whether there is a gender predilection for it.
Race
- There is no racial predilection for GS.
Risk Factors
- Risk factors for GS are usually chromosomal aberrations and include[4]:
- Trisomy 8
- Monosomy 7
- MLL gene rearrangement
- NPM1 mutations
- FLT3 mutations
Natural History, Complications and Prognosis
- How GS evolves over time depends on the co-occurence of the disease with other malignancies.
- GS may present before evidences of other malignancies manifest or after these malignancies are evident.
- Symptoms of the isolated GS depends on the location and the site of the tumor.
- Majority of cases are associated with AML or other myeloproliferative/myelodysplastic syndromes.
- Majority of GS tumors are found in the soft tissues such as the peritoneum, lymph nodes, CNS and skin. They are also found in bone and periosteum.
- Early clinical features include weight loss, weakness. Other manifestations of the tumor depend on its size and location.
- Prognosis of GS depends on its association with other malignacies. In cases of isolated GS the prognosis is good. However, GS associated with myeloproliferative disorders has poor prognosis.
- Prognosis of isolated GS with chromosome 8 abnormalities is worse than other cases of isolated GS.
Diagnosis
Diagnostic Criteria
- There are no predefined criteria for diagnosis of granulocytic sarcoma.
- Granulocytic sarcoma must be suspected in patients with AML or myelodysplatic syndromes. Diagnosis must be confirmed with histopathologic study of the specimen.
Symptoms
- Symptoms of GS may include the following:
- Symptoms due to mass effect such as deafness, ptosis, altered vision, intestinal obstruction, etc.
- Headache, neck pain, abdominal pain,etc. based on the site of the tumor
- Constitutional symptoms such as fever, fatigue, etc.
Physical Examination
- Patients with GS can present with varying presentations.
- Physical examination may be remarkable for:
- Lymph node enlargement (in cases associated with AML and other myeloproliferative syndromes)
- Skin lesions (of varying colors such as green, grey, brown, etc.)
- Organ enlargement such as hepatosplenomegaly.
- Petechiae in patients with thrombocytopenia
- Hearing loss
- Heart murmurs in cases with heart chamber masses
- Crackles on lung auscultation
- Abdominal distention/tenderness in cases with intestinal obstruction
- Limb swelling due to different pathologies such as deep vein thrombosis (DVT).
Laboratory Findings
- In cases associated with AML/CML anemia, thrombocytopenia with normal, low or high white blood cells can be present.
- In cases associated with polycythemia vera, thrombocytosis and high levels of hemoglobin is present in complete blood count (CBC).
- High eosinophil levels can be present in CBC.
Imaging Findings
- In cases of CNS involvement, magnetic resonance imaging (MRI) or CT scan of the CNS can reveal extra-axial masses.
- In cases with soft tissue involvement, sonogram of the tissue can reveal the mass.
- GS appears as[5]:
- Hyperdense/isodence to brain/muscle in CT scan without enhancement
- Isointense/hyperintense on T2-weighted MRI
- Isointemse/hypointense on T1-weighted MRI
- Abdominal plain radiogram can reveal obstruction, intussusception, etc.
- Echocardiogram may reveal mobile masses in any heart chamber in cases of heart involvement.
- Chest radiographs can show lymph node enlargement and consolidation.
Other Diagnostic Studies
- Peripheral blood smear can reveal circulating blasts.
- Flow cytometry can help differentiate AML from acute lymphoblastic leukemia (ALL).
- Histopathologic analysis of biopsy specimen retrieved by excision or fine needle aspiration shows abundant myeloblasts.
- Histopathologic analysis of GS lesions reveals high infiltration with myeloblasts.
Treatment
Medical Therapy
- Chemotherapy is the main stain of treatment in patients with GS. Even patients with isolated GS must receive systemic treatment to better the prognosis.
- Patients receiving cytarabine have better prognosis[4].
- Patients with chemotherpeutic regimens accepted for AML had longer period of progression to AML.
- Treatment includes different regimens[6]:
- Idarubicine and cytarabine
- Fludarabine and cytarabine
- Idarubicine and G-CSF
- Cyclophosphamide, cytarabine, topotecan and G-CSF
- All of these therapeutic agents act through DNA damage and interferes with DNA synthesis.
Bone marrow transplantation
- Hematopoietic stemm cell transplantation can be considered as a treatment option following induction chemotherapy in patients with AML[7].
Radiation
- Radiation can be considered as an adjunctive therapy[7].
- Combination of chemotherapy and radiotherapy can be considered in patients with CNS involvement or when rapid regression of symptoms is required.
Surgery
- Surgery alone is not a good treatment strategy for GS.
- Surgery can be considered prior to chemotherapy in patients where debulking can better the prognosis and help with symptom relief[8].
- Surgery can also have a diagnostic role in cases where excision of the mass provides specimen for histopatjologic diagnosis.
Prevention
- There are no primary preventive measures available for GS.
References
- ↑ Burns, Allen. "Observations of surgical anatomy, in Head andNeck". London, England, Royce, 1811: 364–366.
- ↑ Dock G, Warthin AS. "A new case of chloroma withleukemia". Trans Assoc Am Phys, 1904. 19:64: 115.
- ↑ Rappaport H (1967). Tumors of the hematopoietic system, inAtlas of Tumor Pathology, Section III. Washington: Fascicle 8. ArmedForces Institute of Pathology. pp. 241–247.
- ↑ 4.0 4.1 Daniela Dörfel; et al. (2016). "Cardiac Myeloid Sarcoma: Multimodality Radiologic Imaging Features and Pathologic Correlation". The American Journal of Medicine. 129: e117–e120.
- ↑ Guermazi; et al. (2002). "Granulocytic sarcoma (chloroma): imaging findings in adults and children". American Journal of Roentgenology. 178: 319–25.
- ↑ Yilmaz, A. F., Saydam, G., Sahin, F., & Baran, Y. (2013). "Granulocytic sarcoma: a systematic review". American Journal of Blood Research.
- ↑ 7.0 7.1 Richard L. Bakst, Martin S. Tallman, Dan Douer and Joachim Yahalom (2011). "How I treat extramedullary acute myeloid leukemia". Blood. 118: 3785–3793.
- ↑ Antic D; et al. (2013). "Is there a "gold" standard treatment for patients with isolated myeloid sarcoma?". Biomed Pharmacother. 67: 72–77.