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{{Empty section|date=July 2022}}
{{Empty section|date=July 2022}}
Infantile myofibromatosis is an extremely rare disease, the majority of published literature is based on small cohorts or case reports.<ref name=":3" /> There is a need for a systematic review to be published to help physicians in their clinical decision making when treating IM<ref name=":3" /> <ref name=":6">{{Cite journal |last=Römer |first=Tristan |last2=Wagner |first2=Norbert |last3=Braunschweig |first3=Till |last4=Meyer |first4=Robert |last5=Elbracht |first5=Miriam |last6=Kontny |first6=Udo |last7=Moser |first7=Olga |date=2021 |title=Aggressive infantile myofibromatosis with intestinal involvement |url=https://doi.org/10.1186/s40348-021-00117-9 |journal=Molecular and Cellular Pediatrics |volume=8 |issue=1 |pages=7 |doi=10.1186/s40348-021-00117-9 |issn=2194-7791 |pmc=PMC8208328 |pmid=34132909}}</ref> Because tumor regression is a common characteristic of IM, many physicians take the 'wait and see' approach before actively treating IM with chemotherapy. This method comes into question when IM infiltrates organ systems, becoming life-threatening. Treatment with chemotherapy has shown to be effective in promoting tumor regression but it comes with a risk of toxicities. Treatment with a tyrosine kinase inhibitor (TKI) may be a possibility in patients with the p.Arg561Cys mutation which results from a point mutation on the ''PDGFRB'' gene. TKIs such as imatinib pose less potential toxicities than chemotherapy treatment, but there is still a possibility of stunted growth. <ref name=":6" />
Infantile myofibromatosis is an extremely rare disease, the majority of published literature is based on small cohorts or case reports. There is a need for a systematic review to be published to quantify the prevalence of ''PDGFRB'' variants in patients diagnosed with the disease.<ref name=":3" />


== See also ==
== See also ==

Revision as of 01:11, 31 July 2022

Diffuse infantile fibromatosis is a rare condition affecting infants during the first 3 years of life. It is usually confined to the muscles of the arms, neck, and shoulder area.[1]: 607  There is a multicentric infiltration of muscle fibers with fibroblasts resembling those seen in aponeurotic fibromas.[1]: 607  The term "diffused infantile fibromatosis was initial coined by F.M. Enzinger

Classification

Fibromatoses as are recurring non-metastasizing tumor growth. They are classified as adult fibromatosis and juvenile fibromatosis.[2]

Diffuse Infantile fibromatosis is classified as a subset of juvenile/infantile fibromatosis. Infantile fibromatosis is a rare, genetic disorder of the skin, bone, muscle, soft tissue, and internal organs in young children caused by mutations in the genes PDFRB and NOTCH3. It is characterized by benign tumor growth in the affected organ. Although the tumors do not spread, they may obstruct the functions of surrounding organs and impair their functions. Cases of infantile fibromatosis appear earlier in life however in rare cases it may onset in adulthood. There are treatments available which vary depending on the location of the tumor—surgery being the main one.[3]

Signs and symptoms

The severity of infantile fibromatosis can vary. Although infantile fibromatosis tumors are benign, these tumors can grow in large masses and damage organs as they expand.[4] Some early signs and symptoms can be observed in early stage of infancy (90% of the cases are observed in children under 2 years of age). Infantile fibromatosis can be as categorized by lesions are that are firm, non-tender, skin that maybe purple or red in color and appears as ulcerated and crusted. According to the National Organization for Rare Disorders (NORD), infantile myofibromatosis can be categorized into different forms. The most common form of infantile myofibromatosis is known as the solitary form. This is mostly found in males around the head, neck or trunk areas. While the lesions are mostly seen on the surface of the skin, it can also extend into the subcutaneous tissue and/or muscle tissue. The second form of infantile myofibromatosis is called the multicentric form without visceral involvement. This form is more commonly found in females, and it is characterized by having multiple nodules that can occur on the skin, subcutaneous tissue and/or muscle. The most severe form of infantile myofibromatosis, however, is known as multicentric form with visceral involvement because it usually symbolizes many organs are involved, and the growth of the lesion is widespread. This can be categorized as having multiple growths of the skin, muscles, and even internal organs or structures such as the bones, lung, heart, and the GI tract. In this form, life-threatening complications can arise.[3][5]

Causes

For the majority of cases, infantile myofibromatosis (IM) manifests spontaneously without a known cause. Rarely, multiple family members present with the disorder. In these instances, mutations/variants in the PDGFRB and NOTCH3 genes have been identified as causative.[6] In familial cases of IM, a mutation in the PDGFRB gene was discovered in 18/19 families .[7] Mutations in the NOTCH3 are less common, to date only one family with IM has been identified to have the mutation.[8]

These mutations are caused by errors in DNA replication and they can be either germline or somatic.[9] Germline mutations occur in sperm or egg cells meaning that the mutation can be passed down to future generations. While somatic mutations occur after fertilization during a time of rapid cell division and development. Somatic mutations cannot be passed down to offspring because they do not occur in germ cells (sperm and egg).[9] [10]

IM can present as an autosomal dominant or recessive disorder. It presents as an autosomal dominant disorder when there is either a germline or somatic mutation in one copy of the PDGFRB gene.[6] IM manifests as an autosomal recessive disorder in individuals who inherited two mutated NOTCH3 genes.[8]

Mechanism

Although the exact mechanism of diffuse infantile myofibromatosis is not known, mutations in autosomal inherited genes, PDGFRB and NOTCH3, are suspected to play a big role in the formation of the disorder.

Myofibromatosis refers to the formation and growth of rare tumors in various parts of the body, including the skin and bones. Tumors form through abnormal and excessive cell growth and division, which can lead to a variety of disorders and diseases, like myofibromatosis and cancer.[11]

Diagnosis

Diagnosis of diffuse infantile myofibromatosis requires microscopic tissue examination as well as a physical examination of the individual.[3] Tumor growth is monitored using imaging software like ultrasound and MRI to visualize the tumor progression, regression, and can be useful in diagnosing recurrence of a tumor. The imaging software allows surgeons to pinpoint the location of the tumors and the extent of the lesions to properly evaluate the size. In order to diagnose infantile myofibromatosis, a tissue sample must be removed from the tumor and be identified as infantile myofibromatosis as opposed to other growths that may look similar in the images produced by the imaging softwares.[3]

Genetic testing can identify the likelihood of someone getting the disease.[3]

Prevention and screening

This disorder is not known to be preventable but screening for potential abnormalities at birth can help to identify tumor formation and monitor its severity.

As the disorder is known to be generational, prenatal screening ultrasounds can be conducted for families with at least one parent carrying a PDGFRB variant. Collecting a detailed family history and conducting physical examinations, ultrasounds, and genetic sequencing of PDGFRB gene in tumors is also recommended following diagnosis.[12]

Treatment and management

While tumor might grow slowly (or even shrink over time) and does not require any intervention, surgery is the most direct treatment option to remove the tumor to prevent organ damage. As tumor expands and grows bigger in size, it can lead to life-threatening complications and damage to organs, such as the bones, heart, and lung. Another treatment option is chemotherapy, and it is recommended when surgery is not an viable treatment option.[13] However, in the study "Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series", the pharmacokinetic parameters of vinblastine (a chemotherapy medication) were studied among four infants with the age ranging between 3-3.5 weeks at the first dose of vinblastine. The study states that chemotherapy dose adjustment for infants is extremely difficult mainly due to the lack of age-specific pharmacokinetic data sets, and further study needs to be performed in order to establish an evidence-based dosing guidelines for infants.[14]

Outcomes and prognosis

There is a relatively good prognosis for solitary and multicentric myofibromatosis without visceral involvement. This is due to the spontaneous regression of tumors occurring which generally occurs within 18 to 24 months after diagnosis.[15][16][17] In multicentric myofibromatosis with visceral involvement multiple organs can be affected, resulting in a high rate of mortality for this patient population.[16] Published cohorts of 28 to 31 children with multicentric myofibromatosis with visceral involvement reported mortality rates of 76-93%. The high rates were mostly attributed to cardiopulmonary and gastrointestinal complications.[17]

Epidemiology

As a rare condition, this disorder is known to affect less than 3,000 people in the United States.[6]

History

Special populations

It is unclear what specific populations are affected by this disorder as it can be misdiagnosed pre-natal or at birth. Infantile myofibromatosis, however, is reported to affect males and females and has been known to affect a variety of ethnicities and geographical groups.[3]

Research directions

Infantile myofibromatosis is an extremely rare disease, the majority of published literature is based on small cohorts or case reports.[17] There is a need for a systematic review to be published to help physicians in their clinical decision making when treating IM[17] [18] Because tumor regression is a common characteristic of IM, many physicians take the 'wait and see' approach before actively treating IM with chemotherapy. This method comes into question when IM infiltrates organ systems, becoming life-threatening. Treatment with chemotherapy has shown to be effective in promoting tumor regression but it comes with a risk of toxicities. Treatment with a tyrosine kinase inhibitor (TKI) may be a possibility in patients with the p.Arg561Cys mutation which results from a point mutation on the PDGFRB gene. TKIs such as imatinib pose less potential toxicities than chemotherapy treatment, but there is still a possibility of stunted growth. [18]

See also

References

  1. ^ a b James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  2. ^ Allen PW (September 1977). "The fibromatoses: a clinicopathologic classification based on 140 cases". The American Journal of Surgical Pathology. 1 (3): 255–70. doi:10.1097/00000478-197709000-00007. PMID 920873. S2CID 41764536.
  3. ^ a b c d e f Sencen L. "Infantile Myofibromatosis". NORD (National Organization for Rare Disorders). Retrieved 2022-07-28.
  4. ^ "Infantile Myofibromatosis - NCI". www.cancer.gov. 2020-07-22. Retrieved 2022-07-28.
  5. ^ Larralde M, Ferrari B, Martinez JP, Barbieri MA, Méndez JH, Casas J (December 2017). "Infantile myofibromatosis". Anais Brasileiros de Dermatologia. 92 (6): 854–857. doi:10.1590/abd1806-4841.20175001. PMC 5786406. PMID 29364448.
  6. ^ a b c Sencen L. "Infantile Myofibromatosis". NORD (National Organization for Rare Disorders). Retrieved 2022-07-25.
  7. ^ Guérit E, Arts F, Dachy G, Boulouadnine B, Demoulin JB (April 2021). "PDGF receptor mutations in human diseases". Cellular and Molecular Life Sciences. 78 (8): 3867–3881. doi:10.1007/s00018-020-03753-y. PMID 33449152. S2CID 231612187.
  8. ^ a b Wu D, Wang S, Oliveira DV, Del Gaudio F, Vanlandewijck M, Lebouvier T, et al. (January 2021). "The infantile myofibromatosis NOTCH3 L1519P mutation leads to hyperactivated ligand-independent Notch signaling and increased PDGFRB expression". Disease Models & Mechanisms. 14 (2): dmm046300. doi:10.1242/dmm.046300. PMC 7927659. PMID 33509954.
  9. ^ a b "Infantile myofibromatosis - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-07-28.
  10. ^ "Somatic Mutation vs. Germline Mutation". Cleveland Clinic. Retrieved 2022-07-29.
  11. ^ "How do tumors grow and spread?". UMass Chan Medical School. MCCB. 28 August 2015. Retrieved 2022-07-26.
  12. ^ Hettmer S, Dachy G, Seitz G, Agaimy A, Duncan C, Jongmans M, et al. (October 2021). "Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group". Familial Cancer. 20 (4): 327–336. doi:10.1007/s10689-020-00204-2. PMC 8484085. PMID 32888134.
  13. ^ "Infantile Myofibromatosis - NCI". www.cancer.gov. 2020-07-22. Retrieved 2022-07-26.
  14. ^ Carruthers V, Barnett S, Rees R, Arif T, Slater O, Ramanujachar R, et al. (July 2022). "Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series". Pediatric Blood & Cancer. 69 (7): e29722. doi:10.1002/pbc.29722. PMID 35441483. S2CID 248263569.
  15. ^ Mashiah J, Hadj-Rabia S, Dompmartin A, Harroche A, Laloum-Grynberg E, Wolter M, et al. (August 2014). "Infantile myofibromatosis: a series of 28 cases". Journal of the American Academy of Dermatology. 71 (2): 264–270. doi:10.1016/j.jaad.2014.03.035. PMID 24894456.
  16. ^ a b Mynatt CJ, Feldman KA, Thompson LD (September 2011). "Orbital infantile myofibroma: a case report and clinicopathologic review of 24 cases from the literature". Head and Neck Pathology. 5 (3): 205–215. doi:10.1007/s12105-011-0260-4. PMC 3173528. PMID 21512784.
  17. ^ a b c d Hettmer S, Dachy G, Seitz G, Agaimy A, Duncan C, Jongmans M, et al. (October 2021). "Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group". Familial Cancer. 20 (4): 327–336. doi:10.1007/s10689-020-00204-2. PMC 8484085. PMID 32888134.
  18. ^ a b Römer, Tristan; Wagner, Norbert; Braunschweig, Till; Meyer, Robert; Elbracht, Miriam; Kontny, Udo; Moser, Olga (2021). "Aggressive infantile myofibromatosis with intestinal involvement". Molecular and Cellular Pediatrics. 8 (1): 7. doi:10.1186/s40348-021-00117-9. ISSN 2194-7791. PMC 8208328. PMID 34132909.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
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