Small round cell tumours

Micrograph showing a small round cell tumour (Ewing sarcoma) in the lung. H&E stain.

Small round cell tumours (SRCT), also small round blue cell tumours (SRBCT), are a group of tumours that have a similar histologic appearance.

General

Group of tumours that is typically seen in childhood and younger adults.
Most common small round cell tumour is non-Hodgkin lymphoma.^[1]

A short differential diagnosis of small round cell tumours

A short DDx of SRCTs:^[2]^[3]

Neuroblastoma.
Wilms tumour (AKA nephroblastoma).
Alveolar rhabdomyosarcoma.
Ewing sarcoma / primative neuroectodermal tumour (PNET).
Lymphoma - non-Hogkin's lymphoma, usu. large cell lymphomas (e.g. diffuse large B cell lymphoma, anaplastic large cell lymphoma), Burkitt's lymphoma.
Retinoblastoma.
Hepatoblastoma.
Desmoplastic small round cell tumour (DSRCT).
Small cell carcinoma.

Others:

Memory device: 4 -blastomas (hepato-, neuro-, nephro-, retino-), PNET/Ewing sarcoma (medulloblastoma), LADSSS (lymphoma, alveolar rhabdomyosarcoma, DSRCT, small cell carcinoma, small cell osteosarcoma, synovial sarcoma).

A long differential diagnosis of small blue cell tumours

Adapted from Miller with modifications:^[4]

Tumour	Group	Notes/comments
Malignant melanoma, small cell	melanoma
PEComa	mesenchymal lesion
Carcinoma not otherwise specified	carcinoma
Small cell carcinoma	carcinoma
Merkel cell carcinoma	carcinoma
Islet cell tumour (carcinoid)	carcinoma
Medullary thyroid carcinoma	carcinoma
Desmoplastic small round cell tumour	sarcoma
Polyphenotypic small cell tumour	other
Papillary-cystic tumour of pancreas	other
Pancreatoblastoma	other
Acinar cell carcinoma	carcinoma
Adenoid cystic carcinoma	carcinoma
Cutaneous adnexal tumours (spiradenoma, acrospiroma)	other
Wilms tumour	other
Thymoma	epithelial lesion
Metanephric adenoma of urinary tract	epithelial lesion
Basaloid carcinoma / Basal cell carcinoma	carcinoma
Small cell mesothelioma	carcinoma	^[5]
Pulmonary blastoma	other
Cutaneous myoepithelioma	epithelial lesion	^[6]
Ewing sarcoma / PNET	neural tumours
Neuroblastoma / esthesioneuroblastoma	neural tumours
Sclerosing perineurioma	neural tumours
Schwannoma	neural tumours
Meningioma	neural tumours
Medulloblastoma	neural tumours
Central neurocytoma	neural tumours
Medulloepithelioma	neural tumours
Retinoblastoma	neural tumours
Oligodendroglioma	neural tumours
Pineocytoma	neural tumours
Hemangioblastoma	neural tumours	may be seen extraneural
Neurogenic sarcoma	neural tumours
Lymphoma	lymphoid
Extramedullary leukemia	lymphoid
Plasma cell myeloma	lymphoid
Mastocytosis	lymphoid
Plasmacytoid dendritic cell tumour	lymphoid	CD4 +ve, CD56 +ve^[7]
Granuloma annulare	histiocytic lesion
Seminoma	germ cell tumour	degenerative cases
Granulosa cell tumour	sex cord tumour
Gynandroblastoma	sex cord tumour	Sertoli cell & granulosa cell
Sertoli-Leydig tumour	sex cord tumour
Endometrial stromal sarcoma	sarcoma	may be extragenital
Adenosarcoma	sarcoma	glandular component may not be sampled
Rhabdomyosarcoma	muscle
Skeletal muscle regeneration	muscle	mimics rhabdomyosarcoma^[8]
Small cell leiomyosarcoma	sarcoma
Small cell osteosarcoma	chondro-osseous tumours
Mesenchymal chondrosarcoma	chondro-osseous tumours
Myxoid chondrosarcoma	chondro-osseous tumours
Proliferative myositis	muscle
Fetal or genital rhabdomyoma	other
Glomus tumour	other
Glomangiopericytoma	other
Synovial sarcoma	sarcoma
Hemangiopericytoma	soft tissue lesions
Small cell angiosarcoma	vascular lesions
Epithelioid hemangioendothelioma	vascular lesions
Solitary fibrous tumour	soft tissue lesions	can be myxoid
Myofibroblastoma	soft tissue lesions
Angiomyofibroblastoma	soft tissue lesions

Notes:

This DDx includes small cells that may be spindled.
The DDx for large (non-pleomorphic) epithelioid cells is found in large epithelioid tumours.

Microscopic

Features:

Small cells ~ 2X RBC diameter - key feature.
Scant cytoplasm/high NC ratio.
Sheets of cells, very cellular.
Coarse chromatin.
+/-Nucleolus; usu. not prominent.
+/-Vascularity.

Tabular comparison

Adapted from Thorner:^[9]

Tumour	Key histologic features	History	Key IHC / special stains
Hepatoblastoma	fetal hepatocytes (~ 1:3 NC ratio, eosinophilic cytoplasm)	liver lesion, usu. < 3 years old	AFP
Neuroblastoma	nests, thin fibrovascular septae, lymphocytes, ganglion-like cells (prominent nucleolus), neuropil (eosinophilic, fluffy, finely vacuolated)	adrenal gland, sympathetic chain; usu. < 3 years old	NB-84+, NSE+, S-100-
Nephroblastoma (Wilms tumour)	triphasic - (1) blue cells (blastema), (2) spindle cells (stroma), (3) tubular structures (epithelial)	kidney lesion, various syndromes (e.g. Beckwith-Wiedemann syndrome^[10])	WT-1+
Retinoblastoma	Flexner-Wintersteiner rosette (rosette with empty centre (donut hole))^[11]	eye lesion; +/-RB1 gene mutations (familial)
Medulloblastoma	Homer-Wright rosettes (rosette with a meshwork of fibers (neuropil) at the centre)^[11]	+/-nevoid basal cell carcinoma syndrome; must arise in cerebellum
Ewing sarcoma/PNET	clear cytoplasm (glycogen)	bone lesion, adolescents	PAS+/PASD-, CD99 diffuse membranous
Alveolar rhabdomyosarcoma	alveolar-like spaces (small blue cells line spaces supported by fibrous tissue), rhabdomyoblasts (eosinophilic cytoplasm, +/-cross striations (uncommon), eccentric nucleus, +/-elongated/cigar-shaped cells (uncommon))	adolescents, young adults; often mets at presentation	"DAM" = desmin, actin, myogenin
Embryonal rhabdomyosarcoma^§	nests with rounded border, rhabdomyoblasts (+/-elongated/cigar-shaped cells, eosinophilic cytoplasm, +/-cross striations, eccentric nucleus)	<10 years old; usu. localized	"DAM" = desmin, actin, myogenin
Desmoplastic small round cell tumour (DSRCT)	nests with "jigsaw" border	peritoneum (abdomen or plevis); male > female; locally invasive	keratin+, EMA+, desmin+ !!!
Small cell carcinoma	nuclear moulding, stippled chromatin	adults, smokers	synaptophysin, chromogranin A, CD56, keratins
Lymphoma, non-Hogkin's, usu. large cell (e.g. DLBCL)	dyscohesive cells, usu. ~2x normal (resting) lymphocyte, usu. nucleolus	usu. lymphadenopathy	CD45, CD20, TdT, CD3

Notes:

^§ Uncommonly has the small round cell tumour morphology - included for comparison to alveolar rhabdomyosarcoma.

IHC panel

Gino's panel:^[12]

Lesion	NB84	Myogenin	Desmin	CD99	CD45
Lymphoma	-ve	-ve	-ve	+ve/-ve	+
Ewing sarcoma	+ve/-ve	-ve	-ve	+ve (membranous)	-
Neuroblastoma	+ve	-ve	-ve	+ve/-ve	-ve
Rhabdomyosarcoma	-ve	+ve	+ve	-ve	-ve

More general panel:^[1]

CD45, CD20, CD3, CD99, desmin, EMA, pankeratin, synaptophysin, chromogranin, GFAP.

References

↑ ^1.0 ^1.1 D'cruze, L.; Dutta, R.; Rao, S.; R, A.; Varadarajan, S.; Kuruvilla, S. (Jul 2013). "The role of immunohistochemistry in the analysis of the spectrum of small round cell tumours at a tertiary care centre.". J Clin Diagn Res 7 (7): 1377-82. doi:10.7860/JCDR/2013/5127.3132. PMID 23998069.
↑ URL: http://www.thedoctorsdoctor.com/diseases/small_round_blue_cell_tumor.htm. Accessed on: 2 July 2010.
↑ Chen QR, Vansant G, Oades K, et al. (February 2007). "Diagnosis of the small round blue cell tumors using multiplex polymerase chain reaction". J Mol Diagn 9 (1): 80–8. doi:10.2353/jmoldx.2007.060111. PMC 1867426. PMID 17251339. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867426/.
↑ Miller RT. (Sep 2013). Atlantic Diagnostic Immunohistochemistry Symposium. St. John's, NL, Canada.
↑ Mayall, FG.; Gibbs, AR. (Jan 1992). "The histology and immunohistochemistry of small cell mesothelioma.". Histopathology 20 (1): 47-51. PMID 1310669.
↑ Kutzner, H.; Mentzel, T.; Kaddu, S.; Soares, LM.; Sangueza, OP.; Requena, L. (Mar 2001). "Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of myoepithelial cells.". Am J Surg Pathol 25 (3): 348-55. PMID 11224605.
↑ Reichard, KK.; Burks, EJ.; Foucar, MK.; Wilson, CS.; Viswanatha, DS.; Hozier, JC.; Larson, RS. (Oct 2005). "CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells.". Am J Surg Pathol 29 (10): 1274-83. PMID 16160468.
↑ Guillou, L.; Coquet, M.; Chaubert, P.; Coindre, JM. (Aug 1998). "Skeletal muscle regeneration mimicking rhabdomyosarcoma: a potential diagnostic pitfall.". Histopathology 33 (2): 136-44. PMID 9762546.
↑ PST. 14 February 2011.
↑ URL: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002168/. Accessed on: 4 April 2011.
↑ ^11.0 ^11.1 Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
↑ G. Somers. 22 March 2011.

[pmid23998069-1] 1.0 ^1.1 D'cruze, L.; Dutta, R.; Rao, S.; R, A.; Varadarajan, S.; Kuruvilla, S. (Jul 2013). "The role of immunohistochemistry in the analysis of the spectrum of small round cell tumours at a tertiary care centre.". J Clin Diagn Res 7 (7): 1377-82. doi:10.7860/JCDR/2013/5127.3132. PMID 23998069.

[2] URL: http://www.thedoctorsdoctor.com/diseases/small_round_blue_cell_tumor.htm. Accessed on: 2 July 2010.

[3] Chen QR, Vansant G, Oades K, et al. (February 2007). "Diagnosis of the small round blue cell tumors using multiplex polymerase chain reaction". J Mol Diagn 9 (1): 80–8. doi:10.2353/jmoldx.2007.060111. PMC 1867426. PMID 17251339. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1867426/.

[miller-4] Miller RT. (Sep 2013). Atlantic Diagnostic Immunohistochemistry Symposium. St. John's, NL, Canada.

[pmid1310669-5] Mayall, FG.; Gibbs, AR. (Jan 1992). "The histology and immunohistochemistry of small cell mesothelioma.". Histopathology 20 (1): 47-51. PMID 1310669.

[6] Kutzner, H.; Mentzel, T.; Kaddu, S.; Soares, LM.; Sangueza, OP.; Requena, L. (Mar 2001). "Cutaneous myoepithelioma: an under-recognized cutaneous neoplasm composed of myoepithelial cells.". Am J Surg Pathol 25 (3): 348-55. PMID 11224605.

[pmid16160468-7] Reichard, KK.; Burks, EJ.; Foucar, MK.; Wilson, CS.; Viswanatha, DS.; Hozier, JC.; Larson, RS. (Oct 2005). "CD4(+) CD56(+) lineage-negative malignancies are rare tumors of plasmacytoid dendritic cells.". Am J Surg Pathol 29 (10): 1274-83. PMID 16160468.

[pmid9762546-8] Guillou, L.; Coquet, M.; Chaubert, P.; Coindre, JM. (Aug 1998). "Skeletal muscle regeneration mimicking rhabdomyosarcoma: a potential diagnostic pitfall.". Histopathology 33 (2): 136-44. PMID 9762546.

[9] PST. 14 February 2011.

[10] URL: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002168/. Accessed on: 4 April 2011.

[pmid16551982-11] 11.0 ^11.1 Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.

[12] G. Somers. 22 March 2011.

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Small round cell tumours

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