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2005-02-17-15 Congenital fibrosarcoma © Teodorescu  www.thefetus.net/


Congenital fibrosarcoma

Claudia Elena Teodorescu ,MD
Department of Ultrasound, Calea Floreasca nr. 60 , sect.2 , Bucuresti, Romania

Synonyms:  None

Definition:  Congenital fibrosarcoma is an unusual pediatric spindle-cell tumor of soft tissues that usually presents in the first few years of life. Although these tumors display histological features of malignancy and frequently recur, they have a relatively good prognosis and only rarely metastasize.
Congenital fibrosarcoma is unique among human sarcomas in that it has an excellent prognosis and very low metastatic rate.
It differs from the fibrosarcoma in adulthood by its clinical behaviour: the clinical course of congenital  fibrosarcoma is more favorable and metastatic spread is rare. Localization also differs: while adult fibrosarcomas are common in the thigh, congenital  fibrosarcomas affect chiefly the distal portions of the extremities.
Knezevich reported a novel recurrent t(12;15)(p13;q25) rearrangement in CFS that may underlie the distinctive biologic properties of this tumor
[1]

Case report: This is a woman 35-year-old , G2 P0 . She had several unremarkable ultrasound examinations during the entire pregnancy prior to 30 weeks of gestation. The following images were done at 30 weeks. The rest of the female fetus was normal, as well as the left arm ( last image ).

Images of the right arm:

Image of the left arm:

Postnatal photographs:



She had a resection of the tumor on June 2004, ten days after delivery; she was then treated by chemotherapy. Now she is doing well .

Prevalence:  It is a rare tumor of infant and small child. More than 300 cases have been reported in the literature until 2000, very few of them at birth [2]. Most of the soft tissue sarcomas of childhood other than rabdomyosarcoma, have as final diagnosis fibrosarcoma, specially in the first months of life [3].

Neonatal tumors (tumors that occur within the first 28 days of life or at less than 44 weeks of gestational age) make up 2% of childhood malignancies .The incidence varies from 17 to 121 per million live birth. Teratoma (23.5%) and neuroblastoma (22.5%) are the main types, followed by soft tissue sarcoma (8.1%), renal tumors (7.1%), central nervous system tumors and leukemia (5.9% each).
Soft tissues tumors account for 7% of the malignant tumors in childhood and fibro- and myoblastic tumors account for 12% of the soft tissues tumors in childhood.

Etiology: For many years, it has been the hope, expressed in many epidemiological studies, to identify the cause or causes of malignancies that occur in early life. In particular, the limited temporal nature of intrauterine development provides a unique opportunity to identify carcinogenic stimuli. Fetal and/or maternal exposure to exogenous factors, including ionizing irradiation, drugs and viruses, may start the biological mechanisms responsible for tumor formation [4].

A genetic model of carcinogenesis has also been introduced in an attempt to clarify the pathogenesis and behavioral peculiarities of certain embryonic tumors. According to this hypothesis, embryonal neoplasms   arise as a result of two mutational events in the genome. The first mutation is prezygotic in familial cases and postzygotic in non-familial; the second mutation is always postzygotic [5].

Pathogenesis: Malignant tumors, even in newborns, are mostly genetically based at a cellular level.
Neoplastic transformation of cells in tissue culture and in vivo carcinogenesis are dynamic, multistep and complex processes that can be separated artificially into three phases: initiation, promotion and progression. These phases may be applied to the natural history of virtually all human tumors, including embryonic ones. Initiation is the result of exposure of cells or tissues to an appropriate dose of a carcinogen; an initiated cell is permanently damaged and has a malignant potential. The initiated cells can persist for months or years before becoming malignant. During the promotion phase initiated cells clonally expand. Promotion may be modulated or reversed by a variety of environmental conditions. In the last phase, progression, the transformed cells develop into a tumor, ultimately with metastasis. Embryonic tumors can therefore, be regarded as defects in the integrated control of cell differentiation and proliferation. Congenital fibrosarcoma is characterized by chromosomal translocation and specific gene fusion resulting in dysregulated TrcC expression. Cytogenetic characteristics are sometimes different from older children and may explain the different clinical course [5]
Mutations are inherited from parents or occur as the result of a de novo mutational event. Constitutional chromosomal abnormalities result in an increased risk of malignancy, determine syndromes with increased risk or induce susceptibility to oncogenic factors [6].

Sonographic findings:
- Heterogeneous and vascularized soft tissue mass, poorly circumscribed, with rapid growth
- Deformity of the anatomical region where it develops
- Polyhydramnios (some times)
- Localization: most frequent limbs 42% (inferior more frequent), trunk 31% , head and neck 19% , abdomen & retroperitoneum 8% .
- Rest of the fetus is usually normal. It can be associated with congenital malformations.

Differential diagnosis include (the bold ones are most frequent):
- rhabdomyosarcoma
- hemangiomas
- vascular hamartosis
- lymphangioma
- infantile myofibromatosis
- infantile hemangiopericytoma
- lipoblastomatosis
- fibrous hamartoma of infancy
- teratoma
- fibrous histiocytomas
- lymphangiomatosis
- fibromatosis colli

In a review of 190 soft tissue tumors in infants between birth and 12 months of age, 75% of cases were benign with the majority of cases being hemangioendothelioma (64% including 32% of capillary hemangioma), lymphangioma (29%) , and fibromatosis-myofibromatosis. Fibrous histiocytoma and lipoblastoma were the next two less common lesions. Infantile fibrosarcoma is considered a borderline tumor (it can metastasis, but do so rarely). The embryonal rhabdomyosarcoma and peripheral primitive neuroectodermal tumor are the most common malignant soft tissue tumors [7]

Associated anomalies: Possible association with congenital malformations (the concept that teratogenesis and oncogenesis have shared mechanisms is well documented by numerous examples).

Prognosis: Although these tumors display histological features of malignancy and frequently recur, they have a relatively good prognosis and only rarely metastasize.
Better if t(12 ;15) (p13 ; q25 ) translocation is found.
Recurrence: 5-50%
Metastasis : 0-25% ( 8% for limbs localization , 26% for axial localization )
Mortality rate : 23%
Five years survival is 84 -93% .
One case of spontaneous regression of neonatal fibrosarcoma is cited [8].

Management: Large resection of the tumor after birth (sometimes amputation),chemotherapy.

References:

1 ] Knezevich, S. R.; McFadden, D. E.; Tao, W.; Lim, J. F.; Sorensen, P. H. B. A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nature Genet.1998 18: 184-187.
2 ] Sah SP, Agrawal CS, Rani S. Congenital infantile fibrosarcoma of the upper extremity. Indian J Pathol Microbiol. 2000 Jul;43(3):347-9.
3 ] Leal N, Lopez JC, Diaz M, Ros Z, Perez Alonso P, Tovar J. Congenital fibrosarcoma. Diagnostic-therapeutic implications. J. Cir Pediatr. 2000 Oct;13(4):156-8.
4 ] Court Brown W.M., Doll, R., Hill, A.B. Incidence of leukemia after exposure to diagnostic radiation in utero. BMJ 1960; 2:1539.
5 ] Knudson A.G. Mutagenesis and embryonal carcinogenesis. Natl Cancer Inst Monogr 1979; 51:19.
6] S.W. Moore, D. Satge, A.I. Sasco, et al. The epidemiology of neonatal tumors . J. Pediatr Surg Int 2003 September 19:509-519.
7 ] Coffin CM, Dehner LP. Soft tissue tumors in first year of life: a report of 190 cases. Pediatr Pathol. 1990;10(4):509-26.
8 ] Madden NP, Spicer RD, Allibone EB, Lewis IJ. Spontaneous regression of neonatal fibrosarcoma. Br J Cancer Suppl. 1992: Aug; 18:S72-5.

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