Retroperitoneal extraosseous peripheral primitive neuroectodermal tumor in a Formosan serow: case report and literature review

Abstract

A 10-y-old female captive Formosan serow (Capricornis swinhoei) was inactive and was azotemic. An autopsy was performed following her death, and multiple irregularly shaped, white-to-gray masses of 0.5–2 cm diameter were noted on both ureters, the left adrenal gland, urinary bladder, and uterus. Microscopically, organs were effaced by a poorly demarcated, highly infiltrative neoplasm, composed of neoplastic round cells arranged in islands, sheets, or nests with occasional rosette formation. The neoplastic cells were small: ≤2 red blood cell (≤ 15 μm) diameter. The neoplastic cells were positive for CD56, CK, FLI-1, and NSE, but negative for desmin, GFAP, melan A, NF, PAX-8, S100, synaptophysin, and vimentin. Therefore, the diagnosis of retroperitoneal extraosseous peripheral primitive neuroectodermal tumor (pPNET) was made. pPNET with FLI-1 expression has not been reported previously in animals, to our knowledge.

Keywords

Formosan serow Friend leukemia integration 1 peripheral primitive neuroectodermal tumor

Primitive neuroectodermal tumors (PNETs) are highly malignant tumors composed of small round cells, originating from multipotent progenitor cells of the neuroectoderm.^13,18 Based on anatomic location, PNETs are categorized as central nervous system PNETs (such as medulloblastomas) and peripheral PNETs (pPNETs).^12,13,26 pPNETs can arise from a variety of anatomic locations and can be subdivided into 2 types: extraosseous and osseous. In humans, the most common site of extraosseous pPNETs is the thoracopulmonary region (namely Askin tumors), but extraosseous pPNETs at other anatomic locations, such as the head, neck, kidney, and retroperitoneal or paraspinal regions, have been reported.¹³ PNETs usually have divergent phenotypic differentiation (neuronal, epithelial, and mesenchymal), and thus they usually have diverse immunohistochemical (IHC) characteristics.^11,13,18,47

In humans, ~90% of PNETs are associated with t(11;22)(q24;q12) translocation, causing fusion between the Ewing sarcoma breakpoint region 1 (EWSR-1) gene on chromosome 22 and the Friend leukemia integration 1 (FLI-1) gene on chromosome 11 (EWS-FLI fusion). This translocation results in juxtaposition of the amino-terminal domain of EWSR-1 to the carboxyl-terminus of FLI-1 and the expression of FLI-1 protein in PNETs.^1,11,13,29 Therefore, IHC staining of FLI-1 has been considered essential for the diagnosis of PNETs. However, no PNET cases in animals with IHC staining of FLI-1 have been reported (Table 1), to our knowledge. We report herein the gross, histologic, and IHC characteristics (especially FLI-1) of an extraosseous pPNET in a Formosan serow (syn. Taiwan serow; Capricornis swinhoei).

Table 1.

Primitive neuroectodermal tumors reported in animals.

Species	Age	Sex	Location	IHC-positive	IHC-negative	Reference
Baboon (Papio papio)	NA	F	Cerebellum	NA	NA	⁵
Brahman crossbred calf	6 mo	NA	Spinal cord	NSE, S100, SYN, vimentin	Chro-A, GFAP	⁴
Colobus monkey (Colobus guereza kikuyuensis)	2 mo	M	Facial region, 4th ventricle, retroperitoneal cavity	GFAP, NSE, SYN	NF	³⁰
Cynomolgus monkey (Macaca fascicularis)	3.5 y	M	Left cerebellar hemisphere and hindbrain	GFAP, NF, NSE, S100, SYN, vimentin	None	³⁴
Dog
Australian Shepherd	9 y	CM	Intraocular	SYN	IRBPd, GFAP, opsin, S-Ag	³⁹
Australian Shepherd	5 mo	M	Left frontal bone	NF	CD18, CD3, CD45, CD45r, CD79a, CD99, chro-A, CK, desmin, melan A, NSE, S100, skeletal myosin, SYN, vimentin	⁸
Beagle	10 mo	F	Intraocular	SYN	IRBPd, GFAP, opsin, S-Ag	³⁹
Border Collie	4 y	SF	Cerebellum	GFAP, NSE, S100, vimentin	Nestin, NF, SYN,	⁴³
Chow Chow	9 y	SF	Intraocular	None	IRBPd, GFAP, opsin, S-Ag, SYN,	³⁹
German Shepherd	1 y	M	Thoracolumbar vertebral column	NSE, SYN	BS-1, CD3, CD45R, CD79a, chro-A, CK, desmin, GFAP, histiocyte antigen, IgG, IgM, melan A, MHC-II, NF, S100, SMA, vimentin	²³
Golden Retriever	2.5 y	F	Left cerebral hemisphere	Vimentin	Chro-A, CK, GFAP, NF, NSE, S100, SYN	²⁵
Labrador Retriever	15 wk	M	Cerebellum and brainstem	β-tubulin, nestin, NSE, S100, SYN, vimentin	GFAP	¹⁹
Labrador Retriever	4 y	CM	Left tympanic bulla, vertebral canal, cranial vault	NSE, vimentin	CD99, CK, GFAP, S100	¹⁶
Labrador Retriever mix	11 y	CM	Intraocular	SYN	IRBPd, GFAP, opsin, S-Ag	³⁹
Malamute	1 y	F	Intraocular	IRBPd, GFAP, opsin, S-Ag, SYN	None	Regan, et al.³⁹
Miniature Dachshund	9.6 y	SF	Cerebrum	β-tubulin, GFAP	Iba1, Oligo-2	³⁵
Mixed	1 y	M	Intraocular	GFAP, SYN	IRBPd, opsin, S-Ag	³⁹
Pointer	6 y	F	Cerebellar vermis region	NSE, S100, vimentin	CD3, CD45, CD79a, CK, GFAP, SYN	⁶
Polish Lowland Sheepdog	2.3 y	CM	Cerebellum	GFAP, S100, vimentin	CD3, CD79a	³³
Rottweiler	2 y	M	Intraocular	SYN	IRBPd, GFAP, opsin, S-Ag	³⁹
Terrier mix	7.4 y	CM	Intraocular	None	IRBPd, GFAP, opsin, S-Ag, SYN	³⁹
Dromedary camel (Camelus dromedarius)	9 y	CM	3rd lumbar vertebra	GFAP, NSE, vimentin	CK, SYN, CD3, CD79a	⁴⁶
Formosan serow	10 y	F	Retroperitoneal cavity	CD56, CK, FLI-1, NSE	Desmin, GFAP, NF, PAX8, S100, SYN, vimentin	Current study
Electric eel (Electrophorus electricus)	NA	NA	Facial region	NA	NA	²⁴
Holstein heifer	18 mo	F	Cerebrum	NSE, vimentin	GFAP, NF, S100, SYN	³¹
Japanese Black cattle	7 y	F	Mandibulopharygeal region	NF, NSE	S100, vimentin	⁴⁴
Jersey cow	2 y	F	Left lateral parietal and cranial vault	GFAP, S100, vimentin	Chro-A, NSE, SYN	³⁷
Kowari (Dasyuroides byrnei)	4.5 y	F	Cerebellum	NA		²
Paint horse	2 y	CM	Scrotum, inguinal canals, retroperitoneal cavity	GFAP, NF, NSE, S100, SYN	CD99, desmin, muscle actin	¹²
Quarter Horse	Adult	M	Brainstem	NA	NA	²⁰
Roe deer (Capreolus capreolus)	10 y	F	Mesencephalon	NF, NSE, SYN	β-tubulin, chro-A, CK, GFAP, NF, S100, vimentin	²⁶
Squirrel monkey (Saimiri sciureus)	>20 y	M	Cerebrum	NF, NSE, vimentin	GFAP, SYN	²²
Striped dolphin (Stenella coeruleoalba)	Juvenile	F	Cerebrum	S100, vimentin	CK, GFAP, NSE, SYN	³
Umbrella cockatoo (Cacatua alba)	NA	F	Cerebellum	SYN	GFAP, NSE, NF	¹⁰

C = castrated male; Chro-A = chromogranin A; CK = cytokeratin; CM = castrated male; F = intact female; FLI-1 = friend leukemia integration 1; GFAP = glial fibrillary acidic protein; IHC = immunohistochemical; IRBPd = interphotoreceptor retinoid-binding protein; M = intact male; mo = month; MHC-II = major histocompatibility complex class II; NA = not available; NF = neurofilament; NSE = neuron-specific enolase; PAX8 = paired-box gene 8; S = spayed female; S-Ag = S-antigen; SF = spayed female SYN = synaptophysin; y = year.

A 10-y-old female captive Formosan serow of the Taipei Zoo was inactive, and blood examination revealed increased serum creatinine (592 µmol/L; reference interval [RI]: 62–141 µmol/L), urea (25.4 mmol/L; RI: 5.0–8.9 mmol/L), and potassium (7.1 mmol/L; RI: 3.5–5.1 mmol/L). The RIs of serum biochemistry were based on previous studies of selected Caprinae species (Chinese goral, Naemorhedus griseus).⁴⁵ The animal did not improve with supportive treatment and was found dead the next day; an autopsy was conducted. Multiple irregularly shaped, white-to-gray masses of 0.5–2 cm diameter were noted on both ureters and extended to peripheral soft tissues and organs in the retroperitoneal space, including the left adrenal gland and sublumbar lymph node (LN), and adjacent organs, including urinary bladder and uterus. The growths infiltrated the lumen of the left ureter and thereby obstructed urinary flow, leading to marked dilation of the left ureter and inducing hydronephrosis of the left kidney. Cut sections of the masses were lobulated and homogeneous beige with a firm texture. The wall of the urinary bladder was hardened with some raised masses of 0.5–1 cm diameter, and the dorsal aspect of the urinary bladder adhered to the uterus. In addition, there was a 0.5 × 0.5 × 0.5 cm raised white-to-yellow nodule on the surface of the liver.

Representative tissue samples were collected from the brain, spinal cord, eyes, tongue, thyroid glands, trachea, tracheobronchial LN, lungs, heart, diaphragm, gastrointestinal tract, spleen, liver, both adrenal glands, whole urogenital tract with sublumbar LN, sciatic nerves, and skeletal muscle. The samples were fixed in 10% neutral-buffered formalin, processed routinely, and sections stained with hematoxylin and eosin. Histologic examination revealed that the masses on the ureters were poorly demarcated and highly infiltrative neoplasms with areas of necrosis; neoplastic round cells were arranged in islands or sheets separated by various amounts of fibrovascular stroma. Peripheral palisading of the neoplastic cells with rosette formation was observed. The neoplastic cells were highly pleomorphic with scant eosinophilic cytoplasm, and their nuclei were hyperchromatic and round-to-ovoid with stippled chromatin and conspicuous nucleoli (Fig. 1). The diameter of the neoplastic cells was ≤ 2 red blood cells (≤ 15 μm diameter). Lymphovascular invasion was noted. Neoplastic cells extensively infiltrated the cortex and medulla of the left adrenal gland, urinary bladder, and uterus. The hepatic nodule was composed of the same neoplastic cell population, indicative of hepatic metastasis. The cell morphology and aggressive behavior of the neoplasm were compatible with malignant small round cell tumor (MSRCT) in humans, a term used for a group of neoplasms characterized by small, round, relatively undifferentiated cells.^36,41

Figure 1.

Retroperitoneal extraosseous peripheral primitive neuroectodermal tumor in a Formosan serow. Peripheral palisading of the neoplastic cells with rosette formation is observed (*). The neoplastic cells have scant eosinophilic cytoplasm and contain a hyperchromatic and round-to-ovoid nucleus with stippled chromatin and conspicuous nucleoli. H&E. Bar = 50 μm.

To identify the cell origin of the neoplasm, an IHC panel was performed. Briefly, deparaffinized tissue sections were heated in retrieval solution (Trilogy; Cell Marque, Rocklin, CA) at 121°C in an autoclave for 15 min. Subsequently, tissue sections were incubated in 2.5% normal goat serum in Tris-buffered saline for 30 min at room temperature and then incubated with antibodies against neuron-specific enolase (NSE; diluted 1:800; clone BBS/NC/VI-H14; Dako, Glostrup, Denmark) at room temperature for 1 h. The sections were then treated with 3% hydrogen peroxide in methanol for 10 min followed by peroxidase-conjugated secondary antibodies for 60 min at room temperature. After exposure to 2% 3,3’-diaminobenzidine (Real DAB⁺ chromogen; Dako) for 3 min, the slides were counterstained with hematoxylin for 30 s. IHC staining for CD56 (diluted 1:50; clone RCD56; Zytomed Systems, Berlin, Germany), CD99 (diluted 1:200; clone PCB1; Novocastra Laboratories, Newcastle upon Tyne, UK), chromogranin A (diluted 1:300; clone Poly; Genemed Biotechnologies, South San Francisco, CA), cytokeratin (CK; diluted 1:400; clone AE1/AE3; Novocastra), desmin (diluted 1:100; clone DE-R-11; Leica Microsystems, Richmond, IL), FLI-1 (diluted 1:100; clone G146-222; BD Biosciences), glial fibrillary acidic protein (GFAP; diluted 1:250; clone GA5; Novocastra), melan A (diluted 1:100; clone A103; Dako), neurofilament (NF; diluted 1:200; clone N52.1.7; Novocastra), paired-box gene 8 (PAX8; diluted 1:100; clone BC12; Biocare Medical, Pacheco, CA), S100 (diluted 1:1000; clone 16/f5; Zytomed Systems), synaptophysin (diluted 1:800; clone 27G12; Novocastra), and vimentin (diluted 1:400; clone V9; Novocastra) was performed in an automated system (BondMax; Leica Microsystems). Normal tissues from this serow were used as internal controls for the IHC staining, including endothelial cells (FLI-1 and CD99), muscular arteries (desmin), adrenal gland (CD56, chromogranin A, synaptophysin), cerebellum (GFAP, NSE, NF, S100), kidney (PAX8), and skin (CK, vimentin). Most of the internal controls from the normal tissue of this serow for the above antibodies, except chromogranin A and CD99, were positive, indicative of good cross-reactivity; we excluded chromogranin A and CD99 from our investigation.

The neoplastic cells had membranous positivity for CD56, cytoplasmic positivity for CK/NSE, and cytoplasmic and/or nuclear positivity for FLI-1 (> 50%; Fig. 2). However, the cells were negative for desmin, GFAP, melan A, NF, PAX8, S100, synaptophysin, and vimentin (Supplementary Table 1). Based on the results of IHC staining patterns and the anatomic location of the neoplasm, we diagnosed PNET with hepatic metastasis and involvement of the left adrenal gland, urinary bladder, and uterus.

Figure 2.

Retroperitoneal extraosseous peripheral primitive neuroectodermal tumor in a Formosan serow. A. Neoplastic cells with membranous positivity for CD56. IHC. Bar = 100 μm. B. Neoplastic cells with cytoplasmic positivity for cytokeratin. IHC. Bar = 100 μm. C. Neoplastic cells with nuclear and/or cytoplasmic positivity for FLI-1 (>50% of cells). IHC. Bar = 100 μm. D. Neoplastic cells with cytoplasmic positivity for neuron-specific enolase. IHC. Bar = 100 μm.

Neoplasms in the MSRCT group are characterized by poorly differentiated small round cells and can be epithelial, mesenchymal, neuroendocrine, melanocytic, or hematopoietic.^36,41 Differential diagnosis of MSRCTs includes desmoplastic small round cell tumor (DSRCT), dysgerminoma, melanoma, nephroblastoma, neuroblastoma, neuroendocrine carcinoma, PNET, round cell sarcomas such as lymphoma, small cell rhabdomyosarcoma, small cell osteosarcoma, and synovial sarcoma. Definitive diagnosis is difficult because neoplasms in the MSRCT group share a similar cell morphology.^28,36,41 Therefore, IHC staining is necessary to make the final diagnosis (Supplementary Table 1). In our case, the cross-reactivity of CD99 and chromogranin A was poor in control tissue; therefore, these stains were excluded. Previous studies in humans have demonstrated that > 20% of PNETs are positive for cytokeratin,^7,11,15,17 suggestive of epithelial differentiation. Therefore, the diagnosis of PNETs cannot be ruled out by the expression of epithelial markers. CD56, also known as neural cell adhesion molecule (NCAM), is a marker for neuroendocrine carcinomas and certain types of lymphomas, and PNET can also be positive for CD56 in some human cases.²⁸ Therefore, the differential diagnosis of our neoplasm was narrowed to neuroblastoma, neuroendocrine carcinoma, and PNET by the IHC markers tested (positive for CD56, NSE, and CK; negative for desmin, PAX8, and vimentin [Supplementary Table 1]).

According to studies of human PNETs, FLI-1 is considered crucial for distinguishing PNETs from other MSCRT.^1,11,27-29 In human studies, FLI-1 is a transcription factor and is generally localized within the nucleus, but it has been detected in the cytoplasm of some cells.³⁸ The cytoplasmic positivity may be associated with either cross-reactivity with a cytoplasmic protein or the presence of FLI-1 protein in the cytoplasm of these cells.³⁸ For the IHC staining of FLI-1, the neoplasm is defined as positive only if > 10% of neoplastic cells have nuclear positivity.¹⁴ Generally, neuroblastoma and neuroendocrine carcinoma are negative for FLI-1, and PNET is positive for FLI-1.^28,29 Therefore, our neoplasm is most likely PNET.

We hypothesize that the ureters and adjacent soft tissue were the primary site of our PNET because they were the most severely affected tissues. The other possible origin was from the spinal nerve roots in the lumbar region. However, considering the infiltrative behavior of our PNET, neoplastic cells would have had to directly invade from the spinal nerve roots to the spinal cord, which we did not observe in our case. Therefore, the spinal nerve roots from the lumbar region were less likely to be the primary location.

Several prognostic factors of PNETs have been reported in humans, such as stage, primary tumor site, size, age, and response to therapy.⁹ Some human studies have suggested that extraosseous pPNETs are highly malignant and have a worse prognosis than osseous pPNETs, and that extraosseous pPNETs of the urinary tract may be more aggressive than those in other anatomic locations.^21,32 Given the aggressive behavior of extraosseous pPNETs, early diagnosis with appropriate medical treatment may be the only way to achieve a relatively good clinical outcome. However, such an outcome is difficult to achieve in captive or free-ranging wild animals.

FLI-1 protein is involved in cell proliferation and tumorigenesis, and it is normally expressed in endothelial cells and hematopoietic cells.^29,40,42 In patients with PNETs, EWS-FLI fusion is present only in the neoplastic cells of PNETs and does not exist in normal cells.⁹ The presence of EWS-FLI fusion plays an important role in the transformation, growth, and metastasis of PNETs.^1,9 Therefore, it may be a useful biomarker for both diagnosis and targeted therapy. PNETs with FLI-1 expression have not been reported in any animal species, to our knowledge, and thus the tumorigenesis and the use of FLI-1 as a biomarker for diagnosis or therapy is poorly studied. Further investigations of cytogenetics (such as the chromosomal translocation of t(11; 22)(q24;q12) in humans) by fluorescence in situ hybridization and/or reverse-transcription PCR in animals with PNET or other common neoplasms are necessary to determine the role of FLI-1 in tumorigenesis and the use of FLI-1 as a marker in animals.

Supplemental Material

Supplemental_material – Supplemental material for Retroperitoneal extraosseous peripheral primitive neuroectodermal tumor in a Formosan serow: case report and literature review

Supplemental material, Supplemental_material for Retroperitoneal extraosseous peripheral primitive neuroectodermal tumor in a Formosan serow: case report and literature review by Yu-Han Hsieh, Yung-Hsiang Hsu, Chen-Yeh Lien, Chen-Hsuan Liu and Wen-Ta Li in Journal of Veterinary Diagnostic Investigation

Footnotes

Acknowledgements

We thank Victor Fei Pang, Chian-Ren Jeng, Fun-In Wang, and Hui-Wen Chang, and Cheng-Shun Hsueh, Phoebe Chi-Fei Kao, and Cheng-Hsin Shih at the Graduate Institute of Molecular and Comparative Pathobiology, National Taiwan University for discussions. We appreciate Ming-Yang Gary Chien at Bond biotech in assisting with IHC staining of our case.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Wen-Ta Li

Supplementary material

Supplementary material for this article is available online.

References

Ahmed

, et al. Immunohistochemical detection of FLI-1 protein expression in Ewing sarcoma/peripheral primitive neuroectodermal tumour: a study of 50 cases. J Pak Med Assoc 2016;66:1296–1298.

Attwood

, et al. Spontaneous malignant neoplasms in dasyurid marsupials. J Comp Pathol 1973;83:569–581.

Baily

, et al. Primitive neuroectodermal tumour in a striped dolphin (Stenella coeruleoalba) with features of ependymoma and neural tube differentiation (medulloepithelioma). J Comp Pathol 2013;149:514–519.

Berrocal

, et al. Primitive neuroectodermal tumor in the spinal cord of a Brahman crossbred calf. Vet Pathol 2005;42:834–836.

Berthe

, et al. A medulloblastoma in a baboon (Papio papio). Lab Anim Sci 1980;30:703–705.

Choi

, et al. Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog. Vet Clin Pathol 2012;41:153–157.

Collini

, et al. Cytokeratin immunoreactivity in 41 cases of ES/PNET confirmed by molecular diagnostic studies. Am J Surg Pathol 2001;25:273–274.

De Cock

, et al. A peripheral primitive neuroectodermal tumor with generalized bone metastases in a puppy. Vet Pathol 2004;41:437–441.

Desai

Jambhekar

NA.

Pathology of Ewing’s sarcoma/PNET: current opinion and emerging concepts. Indian J Orthop 2010;44:363–368.

10.

Dyer

, et al. A primitive neuroectodermal tumor in the cerebellum of an umbrella cockatoo (Cacatua alba). J Avian Med Surg 2003;17:20–26.

11.

Elbashier

, et al. Cytokeratin immunoreactivity in Ewing sarcoma/primitive neuroectodermal tumour. Malays J Pathol 2013;35:139–145.

12.

Facemire

, et al. Peripheral primitive neuroectodermal tumor in a two-year-old paint horse. J Vet Diagn Invest 2012;24:794–796.

13.

Fletcher

. Peripheral neuroectodermal tumors. In: Diagnostic Histopathology of Tumors. 4th ed. Philadelphia, PA: Elsevier, 2013:2032–2063.

14.

Folpe

, et al. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol 2001;25:1061–1066.

15.

Folpe

, et al. Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 2005;29:1025–1033.

16.

Gains

, et al. A primitive neuroectodermal tumor with extension into the cranial vault in a dog. Can Vet J 2011;52:1232–1236.

17.

, et al. Cytokeratin immunoreactivity in Ewing’s sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 2000;24:410–416.

18.

Higgins

, et al. Tumors of the nervous system. In: Meuten

, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell, 2017:834–891.

19.

Himmel

, et al. Pathology in practice. J Am Vet Med Assoc 2017;250:55–58.

20.

Holshuh

, et al. Pineoblastoma, a primitive neuroectodermal tumor in the brain of a horse. Vet Pathol 1982;19:567–569.

21.

Huang

, et al. Primary primitive neuroectodermal tumor of the urinary tract. J Formos Med Assoc 2006;105:1008–1012.

22.

Johnson

, et al. A cerebral primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus). J Med Primatol 1999;28:91–96.

23.

Junginger

, et al. Peripheral primitive neuroectodermal tumour in a dog. J Comp Pathol 2013;149:424–428.

24.

Kagan

, et al. Neuronal embryonal tumors in fish. Vet Pathol 2010;47:553–559.

25.

Katayama

, et al. A case of canine primitive neuroectodermal tumor (PNET). J Vet Med Sci 2001;63:103–105.

26.

Kleinschmidt

, et al. Central nervous system neuroblastoma in a wild deer (Capreolus capreolus). J Comp Pathol 2012;146:283–287.

27.

Lee

, et al. EWS/FLI-1 fusion transcript detection and MIC2 immunohistochemical staining in the diagnosis of Ewing’s sarcoma. Pediatr Pathol Lab Med 1996;16:379–392.

28.

Lin

Prichard

. Handbook of Practical Immunohistochemistry: Frequently Asked Questions. 2nd ed. New York, NY: Springer, 2011.

29.

Llombart-Bosch

, et al. Immunohistochemical detection of EWS and FLI-1 proteins in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression. Appl Immunohistochem Mol Morphol 2001;9:255–260.

30.

Long

, et al. Primitive neuroectodermal tumor in a two-month-old black and white Colobus monkey. Vet Pathol 1998;35:64–67.

31.

Lucas

, et al. Cerebral primitive neuroectodermal tumour in a heifer. J Comp Pathol 2003;128:195–198.

32.

Marinova

Retroperitoneal primitive neuroectodermal tumour (PNET). A case report and review of the literature. Rep Pract Oncol Radiother 2009;14:221–224.

33.

McConnell

, et al. Magnetic resonance imaging findings of an intracranial medulloblastoma in a Polish Lowland Sheepdog. Vet Radiol Ultrasound 2004;45:17–22.

34.

Mukaratirwa

, et al. Spontaneous cerebellar primitive neuroectodermal tumor in a juvenile cynomolgus monkey (Macaca fascicularis). Toxicol Pathol 2012;40:931–934.

35.

Nakamoto

, et al. Case of a miniature dachshund with a primitive neuroectodermal tumor confined to the forebrain region treated with a combination of surgery and chemotherapy. J Vet Med Sci 2016;78:1703–1707.

36.

Patel

, et al. Role of immunohistochemistry in the differential diagnosis of malignant small round cell tumor: a study of 38 cases. Int J Res Med Sci 2017;3:3833–3839.

37.

Patton

, et al. Pathology in practice. Primitive neuroectodermal tumor (PNET) with ependymal differentiation. J Am Vet Med Assoc 2014;244:287–289.

38.

Pusztaszeri

, et al. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues. J Histochem Cytochem 2006;54:385–395.

39.

Regan

, et al. Primary primitive neuroectodermal tumors of the retina and ciliary body in dogs. Vet Ophthalmol 2013;16(Suppl 1):87–93.

40.

Rossi

, et al. Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody. Mod Pathol 2004;17:547–552.

41.

Sharma

, et al. Round Cell tumors: classification and immunohistochemistry. Indian J Med Paediatr Oncol 2017;38:349–353.

42.

Sharrocks

, et al. The ETS-domain transcription factor family. Int J Biochem Cell Biol 1997;29:1371–1387.

43.

Steinberg

, et al. Cerebellar medulloblastoma with multiple differentiation in a dog. Vet Pathol 1998;35:543–546.

44.

Uchida

, et al. Peripheral neuroblastoma and primitive neuroectodermal tumor in Japanese black cattle. J Vet Med Sci 1998;60:871–875.

45.

Weber

. Sheep, goats, and goat-like animals. In: Miller

Fowler

, eds. Fowler’s Zoo and Wild Animal Medicine. Vol. 8. St. Louis, MO: WB Saunders, 2015:645–649.

46.

Weiss

, et al. Peripheral primitive neuroectodermal tumour in a lumbar vertebra and the liver of a dromedary camel (Camelus dromedarius). J Comp Pathol 2009;141:182–186.

47.

Woestenborghs

, et al. Cytokeratin-positive meningeal peripheral PNET/Ewing’s sarcoma of the cervical spinal cord: diagnostic value of genetic analysis. Int J Surg Pathol 2005;13:93–97.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.80 MB