Extramedullary hematopoiesis secondary to malignant solid tumors: a case report and literature review

Figures & data

Figure 1 Changes in CT in the ESCC.

Notes: (A and D) the well-circumscribed mass in right pleura (yellow arrows) and thickened esophageal wall (red arrow) prior to treatment, respectively. (B and E) Reduction in the lesions for the esophageal wall (red arrow) and stabilization of the lesion for the right pleura (yellow arrows) after two cycles of TP chemotherapy. (C and F) Esophageal wall (red arrow) thickness decrease and pleural lesion (yellow arrows) size stability after four cycles of TP chemotherapy.

Abbreviations: CT, computed tomography; ESCC, esophageal squamous cell carcinoma; TP, cisplatin–docetaxel.

Figure 2 (A) Pathocytology of esophageal tissue revealed squamous cell carcinoma. (B and C) Pathocytology of pleural soft tissue showed a few of lymphocytes, erythropoiesis, megakaryocytes, and degraded cells.

Notes: (A and B) H&E staining ×100. Scale bar: 100 µm and (C) H&E staining ×200. Scale bar: 100 µm.

Abbreviation: H&E, hematoxylin and eosin.

Figure 3 Immunohistochemical of pleural mass revealed EMH.

Notes: Immunohistochemical staining ×200. Scale bar: 200 µm. (A) CD15⁺; (B) CD20⁺; (C) CD34⁺; (D) CD30⁺; (E) CD38⁺; (F) CD68⁺; (G) CD7⁺; (H) Ki67⁺ (80–90%); (I) lysozyme⁺; (J) CK5⁻; and (K) CK7⁻.

Abbreviation: EMH, extramedullary hematopoiesis.

Figure 4 Variations in CT in the ESCC 1 month after finishing all the treatments.

Note: (A and B) The stabilization of the right pleural mass (yellow arrows) and decrease of the thickened esophageal wall (red arrow) after the treatment, respectively.

Abbreviations: CT, computed tomography; ESCC, esophageal squamous cell carcinoma.

Figure 5 T2W/TSE sagittal MRI image 1 month after the completion of all the treatments, showing no considerable change in the size of the right pleural lesion (yellow arrow).

Abbreviations: MRI, magnetic resonance imaging; T2W/TSE, T2 weighted/turbo spin echo.

Table 1 Eligibility criteria for the literature review

Condition
• Articles published from 1980 to 2017
• Published in the English language
• Confirmed diagnosis of EMH through pathological examination
• All patients were diagnosed with malignant solid tumors
• Confirmed the location of EMH by imaging and surgery

Abbreviation: EMH, extramedullary hematopoiesis.

Table 2 Summary of the malignant solid tumors

Malignant solid tumor	Total patients, n (%)
Breast cancer	13 (31.0)
Renal cancer	7 (16.7)
Lung cancer	6 (14.3)
Colon carcinoma	3 (7.1)
Liver cancer	2 (4.8)
Endometrial adenosarcoma	2 (4.8)
Prostate cancer	1 (2.4)
Adrenal carcinoma	1 (2.4)
Endometrial carcinoma	1 (2.4)
Cutaneous basal cell carcinomas	1 (2.4)
Bladder carcinoma	1 (2.4)
Kaposi sarcoma	1 (2.4)
Ovarian endometrioid adenocarcinoma	1 (2.4)
Ovarian leiomyosarcoma	1 (2.4)
Melanoma	1 (2.4)

Table 3 Summary of the extramedullary hematopoiesis sites

Sites	Total patients, n (%)
Lymph nodes	8 (19.0)
Liver	7 (16.7)
Kidney	6 (14.3)
Paraspinal region	4 (9.5)
Peritoneum	4 (9.5)
Spleen	3 (7.1)
Pleura	2 (4.8)
Breast	2 (4.8)
Presacral region	2 (4.8)
Bronchia	1 (2.4)
Adrenal gland	1 (2.4)
Endometrium	1 (2.4)
Mesenterium	1 (2.4)
Pancreas	1 (2.4)
Ureter	1 (2.4)

Table 4 Summary of data collected from case reports included in the literature review

Variable	n
Age, years
Mean	52.4
Range	1–84
Gender
Male	13
Female	28
Etiology
Pure malignant solid tumor	31
Malignant solid tumor with hematopathy
Thalassemia	1
Hemolytic anemia	2
Sickle cell anemia	1
Myelofibrosis	6
Thrombotic thrombocytopenic purpura	1
Others	1
Physical examination
Hepatomegaly	3
Splenomegaly	6
Hepatomegaly and splenomegaly	4
Imaging examination
X-ray photography	9
Ultrasound	11
Computed tomography	20
MRI	5
^18F-FDG PET	3
Acquisition of pathologic tissue
Excision	25
Biopsy	14
Autopsy	3
Histopathologic component
Pure EMH	29
Mixed EMH	13
Bone marrow biopsy
Associated with hematopathy	6
Normal bone marrow	4
Therapy method
Surgery	25
Hydroxyurea	1
Blood transfusions	2
Observation	14
Outcome
Stable disease	10
Died of malignancy	6

Note: Mixed EMH is that the EMH was present in the tumor tissues.

Abbreviations: EMH, extramedullary hematopoiesis; ¹⁸F-FDG PET, ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography; MRI, magnetic resonance imaging.

Figure 6 Process for the diagnosis and treatment of EMH in malignant solid tumors.

Abbreviations: CT, computed tomography; EMH, extramedullary hematopoiesis; MRI, magnetic resonance imaging.

Table S1 Summary of the basic characteristics of patients

Citation	Sex	Age	Malignant solid tumor	Location of EMH	Hematopathy	Therapy of EMH	Outcome
Meykler et al^Citation1	M	64	Renal cancer	Pleura	N	None	NA
Bowen et al^Citation2	F	72	Breast cancer	lymph nodes	Y	Surgery	DOM
Pantanow et al^Citation3	M	47	Kaposi’s sarcoma	Pleura	Y	None	SD
Takhar et al^Citation4	F	53	Breast cancer	lymph nodes	N	Surgery	SD
Ardakani et al^Citation5	F	44	EAS	Peritoneum	N	Surgery	SD
Ardakani et al^Citation5	F	30	EAS	Peritoneum	N	Surgery	SD
Ardakani et al^Citation5	F	56	OLMS	Peritoneum	N	Surgery	SD
Ardakani et al^Citation5	F	37	OEC	Peritoneum	N	Surgery	SD
Wang et al^Citation6	F	43	Breast cancer	Breast	N	Surgery	NA
Wang et al^Citation6	F	38	Breast cancer	Breast	N	Surgery	NA
Tokumitsu et al^Citation7	M	52	Lung cancer	Paraspinal region	Y	Blood transfusion	DOM
Yablonski-Peretz et al^Citation8	F	43	Breast cancer	Liver	Y	Blood transfusion	DOM
Lemos et al^Citation9	F	50	Adrenal cancer	Liver	Y	None	NA
Prieto-Granada et al^Citation10	F	41	Breast cancer	lymph nodes	N	Surgery	NA
Prieto-Granada et al^Citation10	F	NA	Breast cancer	lymph nodes	N	Surgery	NA
Prieto-Granada et al^Citation10	F	47	Breast cancer	lymph nodes	N	Surgery	NA
Crider et al^Citation11	M	59	Lung cancer	Pancreas	N	HU	DOM
Tamiolakis et al^Citation12	M	62	Colon cancer	Liver	Y	None	NA
Du et al^Citation13	M	57	Prostate cancer	Spleen	N	None	NA
Hsu et al^Citation14	F	64	Lung cancer	Paraspinal region	N	None	NA
Millar et al^Citation15	F	36	Breast cancer	lymph nodes	N	None	NA
Yang et al^Citation16	F	73	Breast cancer	Mesenterium	Y	None	NA
Talmon et al^Citation17	F	49	Renal cancer	Kidney	N	Surgery	NA
Celik et al^Citation18	F	69	Renal cancer	Kidney	N	Surgery	NA
Orphanidou-Vlachou et al^Citation19	F	55	Renal cancer	Kidney	N	Surgery	NA
Tamm et al^Citation20	M	53	CBCC	Liver	Y	Surgery	NA
Arkadopoulos et al^Citation21	F	75	Breast cancer	Adrenal gland	N	Surgery	NA
Groisman et al^Citation22	F	49	Breast cancer	Spleen	N	Surgery	SD
Dekmezian et al^Citation23	F	1	Liver cancer	Liver	N	Surgery	DOM
Dekmezian et al^Citation23	F	3	Liver cancer	Liver	N	Surgery	NA
Paydas et al^Citation24	M	52	Lung cancer	Paraspinal region	Y	None	NA
Chou et al^Citation25	F	50	Colon cancer	Kidney	N	Surgery	NA
Lewis et al^Citation26	M	71	Renal cancer	Kidney	N	Surgery	SD
Varras et al^Citation27	F	40	Breast cancer	Endometrium	N	Surgery	NA
Lara et al^Citation28	NA	NA	Lung cancer	Bronchia	Y	None	NA
Policarpio-Nicolas et al^Citation29	M	68	Lung cancer	Spleen	N	None	NA
Zorn et al^Citation30	M	62	Renal cancer	Ureter	N	Surgery	NA
Bosco et al^Citation31	F	84	Bladder cancer	Paraspinal region	N	None	SD
Wright et al^Citation32	F	66	EC	Presacral region	Y	None	NA
Vassiliou et a^Citation33	F	65	Colon cancer	Presacral region	N	None	SD
Williamson et al^Citation34	M	81	Renal cancer	lymph nodes and kidney	Y	Surgery	NA
Makoni et al^Citation35	M	36	melanoma	Liver, spine and lymph nodes	N	None	DOM

Abbreviations: CBCC, cutaneous basal cell carcinomas; DOM, died of malignancy; EAS, endometrial adenosarcoma; EC, endometrial cancer; F, female; M, male; N, no; NA, not available; NPC, nasopharyngeal carcinoma; OEC, ovarian endometrioid adenocarcinoma; OLMS, ovarian leiomyosarcoma; SD, stable disease; Y, yes; EMH, extramedullary hematopoiesis; HU, hydroxyurea.

MeyklerSObstfeldAJhalaNVergaraNGuptaPKPleural mass forming extramedullary hematopoiesis masquerading as a malignant neoplasmDiagn Cytopathol2015431299699926303071

 PubMed Web of Science ®Google Scholar

BowenJMPerryAMQuistEAkhtariMExtramedullary hematopoiesis in a sentinel lymph node as an early sign of chronic myelomonocytic leukemiaCase Rep Pathol2015201559497025960906

 PubMedGoogle Scholar

PantanowitzLKupermanMGoulartRAClinical history of HIV infection may be misleading in cytopathologyCytojournal20107720607096

 PubMed Web of Science ®Google Scholar

TakharASNeyAPatelMSharmaAExtramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancerBMJ Case Rep201320138943

 Google Scholar

ArdakaniNMKumarasingheMPSpagnoloDVStewartCJExtramed-ullary hematopoiesis associated with organizing peritoneal hemorrhage: a report of 5 cases in patients presenting with primary gynecologic disordersInt J Gynecol Pathol201433331732224681745

 PubMed Web of Science ®Google Scholar

WangJDarvishianFExtramedullary hematopoiesis in breast after neoadjuvant chemotherapy for breast carcinomaAnn Clin Lab Sci200636447547817127738

 PubMed Web of Science ®Google Scholar

TokumitsuSTokumitsuKKohnoeKTakeyaMTakeuchiTExtramedullary hematopoiesis presenting as mediastinal tumorActa Pathol Jpn19803023153227386205

 PubMedGoogle Scholar

Yablonski-PeretzTSulkesAPolliackAWeshlerZOkonECataneRSecondary myelofibrosis with metastatic breast cancer simulating agnogenic myeloid metaplasia: report of a case and review of the literatureMed and Pediatr Oncol198513292963982370

 PubMedGoogle Scholar

LemosLBBaligaMBenghuzziHACasonZNodular hematopoiesis of the liver diagnosed by fine-needle aspiration cytologyDiagn Cytopathol199716151549034738

 PubMed Web of Science ®Google Scholar

Prieto-GranadaCSetiaNOtisCNLymph node extramedullary hematopoiesis in breast cancer patients receiving neoadjuvant therapy: a potential diagnostic pitfallInt J Surg Pathol201321326426623493877

 PubMed Web of Science ®Google Scholar

CriderSKroszer-HamatiAKrishnanKIsolated pancreatic extramedullary hematopoiesisActa Haematol199899138409490565

 PubMed Web of Science ®Google Scholar

TamiolakisDVenizelosJPrassopoulosPIntrahepatic extramedullary hematopoietic tumor mimicking metastatic carcinoma from a colonic primaryOnkologie2004271656715007251

 PubMedGoogle Scholar

DuEOverstreetKZhouWFine needle aspiration of splenic extramedullary hematopoiesis presenting as a solitary mass. A case reportActa Cytol20024661138114212462096

 PubMed Web of Science ®Google Scholar

HsuFIFilippaDACastro-MalaspinaHDowneyRJExtramedullary hematopoiesis mimicking metastatic lung carcinomaAnn Thorac Surg1998664141114139800847

 PubMed Web of Science ®Google Scholar

MillarEKInderSLynchJExtramedullary haematopoiesis in axillary lymph nodes following neoadjuvant chemotherapy for locally advanced breast cancer--a potential diagnostic pitfallHistopathology200954562262319413641

 PubMed Web of Science ®Google Scholar

YangXBhuiyaTEspositoMSclerosing extramedullary hematopoietic tumorAnn Diagn Pathol20026318318712089730

 PubMedGoogle Scholar

TalmonGAPure erythropoiesis in clear cell renal cell carcinomaInt J Surg Pathol201018654454620667923

 PubMed Web of Science ®Google Scholar

CelikBBulutTSedeleMSezerCKarakusVExtramedullary hematopoiesis within cystic renal cell carcinoma with oncocytic and chromophobe cell types: A case reportOncol Lett20147390991324520308

 PubMed Web of Science ®Google Scholar

Orphanidou-VlachouETziakouri-ShiakalliCGeorgiadesCSExtramedullary hemopoiesisSemin Ultrasound CT MR201435325526224929265

 PubMed Web of Science ®Google Scholar

TammEPRabushkaLSFishmanEKHrubanRHDiehlAMKleinAIntrahepatic, extramedullary hematopoiesis mimicking hemangioma on technetium-99m red blood cell SPECT examinationClin Imaging199519288917773882

 PubMed Web of Science ®Google Scholar

ArkadopoulosNKyriaziMYiallourouAIA rare coexistence of adrenal cavernous hemangioma with extramedullar hemopoietic tissue: a case report and brief review of the literatureWorld J Surg Oncol200971319193247

 PubMed Web of Science ®Google Scholar

GroismanGMLobular Carcinoma of the Breast Metastatic to the Spleen and Accessory Spleen: Report of a CaseCase Rep Pathol20162016516018027672468

 PubMedGoogle Scholar

DekmezianRSneigeNPopokSOrdonezNGFine-needle aspiration cytology of pediatric patients with primary hepatic tumors: a comparative study of two hepatoblastomas and a liver-cell carcinomaDiagn Cytopathol1988421621682854046

 PubMed Web of Science ®Google Scholar

PaydasSSarginOGonlusenGPET CT imaging in extramedullary hematopoiesis and lung cancer surprise in a case with thalassemia intermediaTurk J Haematol2011281606227263943

 PubMed Web of Science ®Google Scholar

ChouSSubramanianVLauHMAchanARenal Anastomosing Hemangiomas With a Diverse Morphologic Spectrum: Report of Two Cases and Review of LiteratureInt J Surg Pathol201422436937323816823

 PubMed Web of Science ®Google Scholar

LewisDJMoulJWWilliamsSCSesterhennIAColonEPerirenal liposarcoma containing extramedullary hematopoiesis associated with renal cell carcinomaUrology19944311061098284868

 PubMed Web of Science ®Google Scholar

VarrasMStylianidoAAkrivisCGalanisPStefanakiSAntoniouNExtramedullary hematopoiesis in the uterine isthmus: a case report and review of the literatureEur J Gynaecol Oncol200223322723012094960

 PubMed Web of Science ®Google Scholar

LaraJFRosenPPExtramedullary hematopoiesis in a bronchial carcinoid tumor. An unusual complication of agnogenic myeloid metaplasiaArch Pathol Lab Med199011412128312852252428

 PubMed Web of Science ®Google Scholar

Policarpio-NicolasMLBregmanSGIhsanMAtkinsKAMass-forming extramedullary hematopoiesis diagnosed by fine-needle aspiration cytologyDiagn Cytopathol2006341280781117115434

 PubMed Web of Science ®Google Scholar

ZornKCOrvietoMAMikhailAASolitary ureteral metastases of renal cell carcinomaUrology2006682428e425427

 Web of Science ®Google Scholar

BoscoMCarucciPPacchioniDEndoscopic ultrasound-guided fine needle aspiration diagnosis of extramedullary hematopoiesis in mediastinumEndoscopy200941Suppl 2E6719177294

 PubMedGoogle Scholar

WrightPKThiryayiSARanaDNFine needle aspiration cytology diagnosis of extramedullary haematopoiesis presenting as a pre-sacral mass: a pitfall avoidedCytopathology201223213313421955299

 PubMed Web of Science ®Google Scholar

VassiliouVPapamichaelDLutzSPresacral Extramedullary Hematopoiesis in a Patient with Rectal Adenocarcinoma: Report of a Case and Literature ReviewJ Gastrointest Cancer201243Suppl 1S13113522318765

 PubMedGoogle Scholar

WilliamsonSRMastKJChengLIdreesMTClear cell renal cell carcinoma with intratumoral and nodal extramedullary megakaryopoiesis: a potential diagnostic pitfallHum Pathol20144561306130924704159

 PubMed Web of Science ®Google Scholar

MakoniSNLaberDAClinical spectrum of myelophthisis in cancer patientsAm J Hematol2004761929315114608

 PubMed Web of Science ®Google Scholar