Spindle cell lesions

A spindle cell lesion (MPNST). H&E stain.

Spindle cell lesions are seen frequent enough that one ought to have a solid approach to 'em.

A general introduction to spindle cells is found in the spindle cell article.

General DDx

Spindle cells should make think:

Nerve.
Muscle.
- Smooth.
- Skeletal.
Other.
- Carcinoma, e.g. metaplastic carcinoma.

A long differential diagnosis of spindle cell tumours

Adapted from Miller with modifications:^[1]

Tumour	Group	Notes/comments
Malignant melanoma	melanoma
PEComa	mesenchymal lesion	angiomyolipoma, lymphangioleiomyomatosis, other PEComas
Sarcomatoid carcinoma	carcinoma
Desmoplastic mesothelioma	carcinoma
Thymoma	epithelial lesion
Spindle epithelial tumor with thymus-like differentiation	epithelial lesion
Malignant phyllodes tumour	sarcoma
Chondroid syringoma	epithelial lesion
Malignant mixed Muellerian tumour	carcinoma
Syphilis	infection
Bacillary angiomatosis	infection
Myocbacterial spindle cell pseudotumour	infection
Cryotococcal pseudotumour	infection
Anaplastic large cell lymphoma	lymphoid
Lymphocyte-depleted Hodgkin lymphoma	lymphoid
Follicular dendritic cell sarcoma	sarcoma
Interdigitating reticulum cell sarcoma	sarcoma
Sclerosing extramedullary hematopoetic tumours	other	seen in chronic myeloproliferative disorders^[2]
Juvenile xanthogranuloma	histiocytic lesion
Granuloma annulare	histiocytic lesion
Crystal-storing histiocytosis	histiocytic lesion
Schwannoma	neural tumours
Neurofibroma	neural tumours
Malignant peripheral nerve sheath tumour	neural tumours
Perineurioma	neural tumours
Sustentaculoma of adrenal gland	neural tumours
Mucosal epithelioid nerve sheath tumour	neural tumours
Neurothekeoma	neural tumours
Angiosarcoma	vascular tumours
Kaposi's sarcoma	vascular tumours
Composite hemangioendothelioma	vascular tumours
Pseudoangiomatous stromal hyperplasia	vascular tumours
Angiolymphoid hyperplasia with eosinophilia	vascular tumours
Kaposiform hemangioendothelioma	vascular tumours
Leiomyosarcoma	muscle tumours
Hyalinizing matrix-rich rhabdomyosarcoma	muscle tumours	DDx: osteosarcoma, chondrosarcoma
Spindle cell rhabdomyosarcoma	muscle tumours
Glomangiopericytoma	muscle tumours
Myopericytoma	muscle tumours
Fetal or genital rhabdomyoma	muscle tumours
Spindle cell lipoma	lipomatous tumours
Spindle cell liposarcoma	lipomatous tumours	^[3]
Massive localized lymphedema	lipomatous tumours	associated with obesity
Dedifferentiated liposarcoma	lipomatous tumours
Lipoleiomyosarcoma	lipomatous tumours	^[4]
Spindle cell osteosarcoma	chondro-osseous tumours
Parosteal osteosarcoma	chondro-osseous tumours
Extraskeletal myxoid chondrosarcoma	chondro-osseous tumours
Fibromatosis	fibroblastic/myofibroblastic tumours
Desmoid tumour	fibroblastic/myofibroblastic tumours
Hemorrhagic dermatomyofibroma	fibroblastic/myofibroblastic tumours
Sclerotic "plywood" fibroma	fibroblastic/myofibroblastic tumours	^[5]
Fibrosarcoma	fibroblastic/myofibroblastic tumours
Dermatofibrosarcoma protuberans	fibroblastic/myofibroblastic tumours
Angiomyofibroblastoma	fibroblastic/myofibroblastic tumours
Myofibroblastic sarcoma, low grade	fibroblastic/myofibroblastic tumours
Solitary fibrous tumour	fibroblastic/myofibroblastic tumours
Superficial acral fibromyxoma	fibroblastic/myofibroblastic tumours
Diffuse-type tenosynovial giant cell tumour	fibroblastic/myofibroblastic tumours
Fasciitis-like reactive myofibroblastic proliferation	fibroblastic/myofibroblastic tumours
Sclerosing epithelioid fibrosarcoma	fibroblastic/myofibroblastic tumours
Myxoinflammatory fibroblastic sarcoma	fibroblastic/myofibroblastic tumours
Dermatomyofibroma	fibroblastic/myofibroblastic tumours
Myofibrosarcoma	fibroblastic/myofibroblastic tumours	^[6]
Myofibromatosis-like perivascular myoma	fibroblastic/myofibroblastic tumours
Myofibroblastoma	fibroblastic/myofibroblastic tumours	superficial cervicovaginal myofibroblastoma^[7]
Cellular Angiofibroma	fibroblastic/myofibroblastic tumours	^[8]
Giant cell angiofibroma	fibroblastic/myofibroblastic tumours
Myofibroma	fibroblastic/myofibroblastic tumours
Ossifying fibromyxoid tumour of soft parts	fibroblastic/myofibroblastic tumours	S-100 +ve
Myxofibrosarcoma	fibroblastic/myofibroblastic tumours
Pleomorphic undifferentiated sarcoma	fibroblastic/myofibroblastic tumours
Atypical fibroxanthoma	fibroblastic/myofibroblastic tumours
Low grade fibromyxoid sarcoma	fibroblastic/myofibroblastic tumours	hyalinizing spindle cell tumour with giant rosettes
Inflammatory myofibroblastic tumour	fibroblastic/myofibroblastic tumours	may be cytokeratin +ve, ALK +ve
Angiomatoid fibrous histiocytoma	fibroblastic/myofibroblastic tumours	younger individuals
Synovial sarcoma	sarcoma
Gastrointestinal stromal tumour	mesenchymal lesion
Meningioma	other	fibrous variant
Epithelioid sarcoma	sarcoma	pseudomyogenic "fibroma-like" variant
Anthracotic & anthracosilicotic spindle cell pseudotumour of mediastinal lymph node	other
Adenosarcoma	sarcoma	under-sampled glandular component
Mixed Muellerian tumour	sarcoma
Blastemal elements of Wilms' tumour	other
Blastemal elements of pulmonary blastoma	other
Ossifying desmoplastic nested epithelial-stromal tumour of liver	other
Phosphaturic mesenchymal tumour	other
Ectomesenchymoma	other	skeletal muscle and neural differentiation
Congenital pseudarthosis associated with neurofibromatosis	other
Endometrial stromal sarcoma	sarcoma
Mixed endometrial stromal and smooth muscle tumour of the uterus	mesenchymal lesion	^[9]
Yolk sac tumour, spindle cell	germ cell tumour
Granulosa cell tumour	sex cord tumour
Thecoma	sex cord tumour
Fibroma	sex cord tumour
Leydig cell tumour, spindle cell	sex cord tumour	^[10]
Gynandroblastoma	sex cord tumour	Sertoli cell tumour & granulosa cell tumour

Microscopic

Grouping by pleomorphism

Monomorphic - small variation of tumour cell size.
Pleomorphic - large variation of tumour cell size.

DDx - monomorphic:

Synovial sarcoma.
Fibrosarcoma.
MPNST.
Metaplastic carcinoma, e.g. metaplastic breast carcinoma.

DDx - pleomorphic:

Pleomorphic undifferentiated sarcoma.
Pleomorphic liposarcoma.
Pleomorphic rhabdomyosarcoma.
Pleomorphic leiomyosarcoma.
Metaplastic carcinoma.
- Metaplastic breast carcinoma.
- Spindle cell squamous carcinoma.
Malignant melanoma.
Others - see pleomorphic tumours for an exhaustive DDx.

Grouping by pattern

See: Basics#Morphologic patterns.

IHC

Basic panel

Dixon panel:^[11]

CD34.
Desmin.
SMA.
S-100.
AE1/AE3 (pankeratin).

Memory device SCADS or CAD SS = S-100, CD34, AE1/AE3, Desmin, SMA.

Big panels

A MSH MFH panel

CD34 - GIST, angiosarcoma, solitary fibrous tumour/hemangiopericytoma, Kaposi sarcoma, DFSP, PASH.
S-100 - neural marker, sensitive for malignant melanoma, Langerhans cells, clear cell sarcoma.
Desmin - smooth muscle.
MIB1 - proliferation.
CD99 - immature T cells (thymus), small round cell tumours, synovial sarcoma, Merkel cell carcinoma, osteosarcoma.^[12]
- Considered "slutty", i.e. non-specific, by Dr. Fletcher; useful if membranous stain pattern = Ewing sarcoma/PNET.
BCL2 - synovial sarcoma, small cell lymphomas, spindle cell lipoma,^[13]^[14] solitary fibrous tumour.
PGP 9.5.
SMMS - smooth muscle.
Caldesmon - muscle.
PDGFR - GIST
DOG1 - GIST (membranous, cytoplasmic),^[15] normal pancreas (islets),^[15] associated with BRCA1.

Others:

Beta-catenin - a small subset of soft tissue lesions:
- Desmoid-type fibromatosis (~70%), solitary fibrous tumour & endometrial stromal sarcoma (~40%), synovial sarcoma (~30%).^[16]

DJH panels

MFH

Vimentin.
Keratin 5D3 - carcinomas.
Keratin LP34 - carcinomas.
EMA.
CD99.
MSA.
SMA.
Caldesmon.
CD34.
S-100 - neural tumours.
HMB45 - melanoma
Mart-1 - melanoma.
Tyrosinase.
MYF-4 - RMS.
Alpha-1-antichymotrypsin.

SRCT

Same as MFH panel plus the following:

CD45.
CD30.
CD3.
CD20.
Desmin.
CD31 - angiosarcoma.
Factor VIII - angiosarcoma.

Treatment

It depends on the subtype.
Malignant lesions are usually sarcomas and treated with radiation and surgery.^[17]

References

↑ Miller RT. (Sep 2013). Atlantic Diagnostic Immunohistochemistry Symposium. St. John's, NL, Canada.
↑ Remstein, ED.; Kurtin, PJ.; Nascimento, AG. (Jan 2000). "Sclerosing extramedullary hematopoietic tumor in chronic myeloproliferative disorders.". Am J Surg Pathol 24 (1): 51-5. PMID 10632487.
↑ Dei Tos, AP.; Mentzel, T.; Newman, PL.; Fletcher, CD. (Sep 1994). "Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases.". Am J Surg Pathol 18 (9): 913-21. PMID 8067512.
↑ Folpe, AL.; Weiss, SW. (Jun 2002). "Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.". Am J Surg Pathol 26 (6): 742-9. PMID 12023578.
↑ Hanft, VN.; Shea, CR.; McNutt, NS.; Pullitzer, D.; Horenstein, MG.; Prieto, VG. (Feb 2000). "Expression of CD34 in sclerotic ("plywood") fibromas.". Am J Dermatopathol 22 (1): 17-21. PMID 10698210.
↑ Montgomery, E.; Goldblum, JR.; Fisher, C. (Feb 2001). "Myofibrosarcoma: a clinicopathologic study.". Am J Surg Pathol 25 (2): 219-28. PMID 11176071.
↑ Ganesan, R.; McCluggage, WG.; Hirschowitz, L.; Rollason, TP. (Feb 2005). "Superficial myofibroblastoma of the lower female genital tract: report of a series including tumours with a vulval location.". Histopathology 46 (2): 137-43. doi:10.1111/j.1365-2559.2005.02063.x. PMID 15693885.
↑ Iwasa, Y.; Fletcher, CD. (Nov 2004). "Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases.". Am J Surg Pathol 28 (11): 1426-35. PMID 15489646.
↑ Oliva, E.; Clement, PB.; Young, RH.; Scully, RE. (Aug 1998). "Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases.". Am J Surg Pathol 22 (8): 997-1005. PMID 9706980.
↑ Ulbright, TM.; Srigley, JR.; Hatzianastassiou, DK.; Young, RH. (Nov 2002). "Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells.". Am J Surg Pathol 26 (11): 1424-33. PMID 12409718.
↑ BD. 1 April 2011.
↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 108. ISBN 978-0470519035.
↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 107. ISBN 978-0470519035.
↑ URL: http://ajp.amjpathol.org/cgi/content/full/160/3/759. Accessed on: 3 August 2010.
↑ ^15.0 ^15.1 Ardeleanu C, Arsene D, Hinescu M, et al. (October 2009). "Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker". Appl. Immunohistochem. Mol. Morphol. 17 (5): 413–8. doi:10.1097/PAI.0b013e31819e4dc5. PMID 19417627.
↑ Ng TL, Gown AM, Barry TS, et al. (January 2005). "Nuclear beta-catenin in mesenchymal tumors". Mod. Pathol. 18 (1): 68–74. doi:10.1038/modpathol.3800272. PMID 15375433.
↑ Collini P, Sorensen PH, Patel S, et al. (August 2009). "Sarcomas with spindle cell morphology". Semin. Oncol. 36 (4): 324–37. doi:10.1053/j.seminoncol.2009.06.007. PMID 19664493.

[miller-1] Miller RT. (Sep 2013). Atlantic Diagnostic Immunohistochemistry Symposium. St. John's, NL, Canada.

[pmid10632487-2] Remstein, ED.; Kurtin, PJ.; Nascimento, AG. (Jan 2000). "Sclerosing extramedullary hematopoietic tumor in chronic myeloproliferative disorders.". Am J Surg Pathol 24 (1): 51-5. PMID 10632487.

[pmid8067512-3] Dei Tos, AP.; Mentzel, T.; Newman, PL.; Fletcher, CD. (Sep 1994). "Spindle cell liposarcoma, a hitherto unrecognized variant of liposarcoma. Analysis of six cases.". Am J Surg Pathol 18 (9): 913-21. PMID 8067512.

[pmid12023578-4] Folpe, AL.; Weiss, SW. (Jun 2002). "Lipoleiomyosarcoma (well-differentiated liposarcoma with leiomyosarcomatous differentiation): a clinicopathologic study of nine cases including one with dedifferentiation.". Am J Surg Pathol 26 (6): 742-9. PMID 12023578.

[5] Hanft, VN.; Shea, CR.; McNutt, NS.; Pullitzer, D.; Horenstein, MG.; Prieto, VG. (Feb 2000). "Expression of CD34 in sclerotic ("plywood") fibromas.". Am J Dermatopathol 22 (1): 17-21. PMID 10698210.

[pmid11176071-6] Montgomery, E.; Goldblum, JR.; Fisher, C. (Feb 2001). "Myofibrosarcoma: a clinicopathologic study.". Am J Surg Pathol 25 (2): 219-28. PMID 11176071.

[pmid15693885-7] Ganesan, R.; McCluggage, WG.; Hirschowitz, L.; Rollason, TP. (Feb 2005). "Superficial myofibroblastoma of the lower female genital tract: report of a series including tumours with a vulval location.". Histopathology 46 (2): 137-43. doi:10.1111/j.1365-2559.2005.02063.x. PMID 15693885.

[pmid15489646-8] Iwasa, Y.; Fletcher, CD. (Nov 2004). "Cellular angiofibroma: clinicopathologic and immunohistochemical analysis of 51 cases.". Am J Surg Pathol 28 (11): 1426-35. PMID 15489646.

[pmid9706980-9] Oliva, E.; Clement, PB.; Young, RH.; Scully, RE. (Aug 1998). "Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases.". Am J Surg Pathol 22 (8): 997-1005. PMID 9706980.

[10] Ulbright, TM.; Srigley, JR.; Hatzianastassiou, DK.; Young, RH. (Nov 2002). "Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells.". Am J Surg Pathol 26 (11): 1424-33. PMID 12409718.

[11] BD. 1 April 2011.

[Ref_DCHH108-12] Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 108. ISBN 978-0470519035.

[Ref_DCHH107-13] Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 107. ISBN 978-0470519035.

[14] URL: http://ajp.amjpathol.org/cgi/content/full/160/3/759. Accessed on: 3 August 2010.

[pmid19417627-15] 15.0 ^15.1 Ardeleanu C, Arsene D, Hinescu M, et al. (October 2009). "Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker". Appl. Immunohistochem. Mol. Morphol. 17 (5): 413–8. doi:10.1097/PAI.0b013e31819e4dc5. PMID 19417627.

[pmid15375433-16] Ng TL, Gown AM, Barry TS, et al. (January 2005). "Nuclear beta-catenin in mesenchymal tumors". Mod. Pathol. 18 (1): 68–74. doi:10.1038/modpathol.3800272. PMID 15375433.

[pmid19664493-17] Collini P, Sorensen PH, Patel S, et al. (August 2009). "Sarcomas with spindle cell morphology". Semin. Oncol. 36 (4): 324–37. doi:10.1053/j.seminoncol.2009.06.007. PMID 19664493.

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