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Revista chilena de pediatría

versión impresa ISSN 0370-4106

Rev. chil. pediatr. vol.89 no.5 Santiago oct. 2018

http://dx.doi.org/10.4067/S0370-41062018005000803 

CLINICAL CASE

Umbilical fibrous hamartoma of infancy: A case report

Paula Muñoz1  2 

Roberto Bustos2 

Jocelyn Manfredi3 

1 Dermatology unit, Hospital Luis Calvo Mackenna, Santiago, Chile.

2 Departament of Dermatology, Faculty of Medicine, University of Chile, Santiago, Chile.

3 Pathological Anatomy Unit, Clínica Santa María, Santiago, Chile.

Abstract:

Introduction:

Fibrous hamartoma of infancy (FHI) is a benign, soft tissue tumor that usually oc curs in children and has a characteristic histological morphology.

Objective:

To describe a case of congenital FHI with atypical histological and clinical characteristics.

Clinical case:

Full-term male newborn, with no perinatal morbid history was referred to dermatology due to a congenital erythe matous plaque in the umbilical region. The histological study showed a fusocelullar proliferation in dermis and hypodermis of biphasic distribution, with an infiltrative, swirling pattern and bundles of spindle fibroblast-like and myofibroblast-like cells, associated in depth with a mature adipose tissue component. The immunohistochemical study revealed diffuse positivity for CD34, and focal posi tivity for FXIIIa, without immunoreactivity for actin, desmin, MyoD1, S100, HMB45, Melan-A, or EMA. Fluorescent in situ hybridization (FISH) was negative for platelet-derived growth factor recep tor beta (PDGFR-beta) and for ETV6 gene. PDGFR-beta and ETV6 gene are present in congenital dermatofibrosarcoma protuberans and infantile fibrosarcoma, respectively. This history, in addition to previous histological findings, supported the diagnosis of FHI. Surgical resection was performed, without signs of recurrence during clinical follow-up.

Conclusion:

It is important to consider the FHI within the differential diagnosis of subcutaneous tumors in children, especially in those under two years of age. Although its behavior is benign, it is similar to multiple benign and malignant le sions, which makes it imperative to perform a histological study in front of suspicious clinical lesions.

Keywords: Fibrous hamartoma of infancy; congenital; umbilical; soft tissue tumour

Introduction

Soft tissue tumors in children are diverse and often complex diagnostic entities. Therefore, an exhaustive clinical evaluation with a complete histological study is essential to differentiate the diverse entities and thus to establish an accurate treatment and prognosis.

Fibrous hamartoma of infancy (FHI) is an uncom mon benign fibroproliferative tumor with a characteristic three-phase morphology1. It was first described by Reye in 1956 as a subdermal fibrous tumor of in fancy2 and was renamed by Enzinger in 1965 with the current name3. The WHO classification of soft tissue tumors defines it as a fibroblastic/myofibroblastic tu mor poorly defined, with a characteristic histologic pattern1.

It usually occurs before the age of two as a single, asymptomatic lesion located in the subcutaneous cellular tissue or in the reticular dermis, and it is diffi cult to differentiate from adjacent healthy tissue4,5. Due to its similarity with several entities, its diagnosis must be confirmed by a histological and immunohistochemical study. However, these methods may have limitations since their findings are sometimes unspe cific.

Although nearly 200 cases have been published in the international literature to date, there are few reports in the Latin American population. The ob jective of this study is to describe a case of congenital FHI in an infant, with atypical clinical and histologi cal characteristics, where additional molecular stu dies were needed to differentiate it from other skin conditions.

Clinical case

Full-term male newborn, controlled pregnancy, eutocic delivery, with no perinatal morbid history. He was referred to the dermatology department due to a slightly infiltrated erythematous plaque in the peri and infra-umbilical region which was present since birth, with well-defined borders and adherent superficial yellowish peeling at the lower pole, without other local inflammatory signs (Figure 1). A skin ultrasound study revealed homogeneous hypoechoic dermoepidermal lesion, with slight extension to the subcutaneous tissue and few sinuous vessels in its deepest segment.

Figure 1 Fibrous hamartoma of infancy: erythematous plaque slightly infiltrated in the peri and infraumbillcal region. 

Given the clinical characteristics, a deep incisio nal biopsy was performed which showed proliferation of thin fusiform cells in dermis and hypodermis, of biphasic morphology with one segment arranged in a infiltrate swirling pattern and another one with fused cell bands with fibroblastic and myofibroblastic appearance, and with absence of Grenz zone (Figure 2 A and B). It presented in depth a component of mature adipose tissue with no signs of atypia (Figure 3). Matu re epidermis, partially atrophic. There was no atypical necrosis or mitosis. The immunohistochemical study of the tumor cells showed intense and diffuse positivity for CD34 (Figure 4) and focal FXIIIa positivity, with the absence of immunoreactivity for actin, desmin, MyoD1, S100, HMB45, MelanA, and EMA. Modera te Ki-67 proliferation index, with positivity in appro ximately 20% of cells. The study was complemented with FISH using PDGF beta and ETV6, which were negative, excluding differential diagnoses of conge nital dermatofibrosarcoma protuberans and infantile fibrosarcoma, respectively. These antecedents, along with the histological findings, were consistent with the diagnosis of FHI.

Figure 2 Optical microscopy. A, with 2x hematoxylin-eosin staining, skin with ma ture, focally atrophic epidermis, associated with a spindle fusocellular lesion, with biphasic embryonic stroma. In B, with 20x hematoxylin-eosin staining, spindle cell in jury with embryonic stroma was observed, forming swirling structures and bands of fused cells. No necrosis or atypical mitosis is observed. 

Figure 3 Optical microscopy. Hematoxylin-eosin stain 4x. Fusocellular lesion associated with mature adipose tissue. 

Figure 4 Optical microscopy. Immunohistochemical study CD34. Positivity is observed in the fused cells, with membrane and cytoplasm pattern. 

Surgical extirpation was performed by the pediatric surgery team, with umbilical readjustment through lateral rotation flaps. The histological and immunohistochemical study supported the previously described findings, compromising margins of surgical resection. The patient evolved without signs of recurrence at se ven months of follow-up (Figure 5).

Figure 5 Fibrous ha martoma of infancy: peri and infraumbilical scar (7 months post surgery). 

Discussion

FHI most frequently affect males4,5, generally oc curring during the first two years of life, with an average age ranging from 15 and 18 months4,5. Although congenital lesions have been described as in our case, they represent between 4-23% of the total according to various reports4,6. It does not show family history and it is not related to other neoplasms or congenital disorders5.

Currently, there are controversies regarding the origin of this entity. Cytogenetic abnormalities involving different chromosomes have recently been identified7-9, supporting the theory that FHI is a neoplastic rather than a hamartomatous process.

Classically, it is presented as a single, mobile, small, poorly limited, asymptomatic, skin-colored, firm no dule with no associated epidermal changes. It is loca ted mainly in armpits, back, and upper extremities4,5. Although most patients share the described characte ristics, multiple lesions6 and changes in adjacent skin have been reported, such as alteration in pigmentation10, hyperplasia of eccrine glands11, and hypertrichosis12. It is interesting in our case the observed epidermal changes, as well as the anatomical location. Generally, the FHI increases in size up to five years and then slows its growth, but without stopping or regressing13. On the other hand, there are reports of accelerated growth during childhood13. However, it is important to note that in most of the published series a smaller percenta ge of patients have completed clinical follow-up.

Histologically, the tumor may be subcutaneous or adhered to the dermis. It is characterized by a variable threephase component of mature fibroblastic-myofibroblastic tissues, immature mesenchymal and mature adipose tissues, frequently associated with chronic in flammatory infiltrate5. These components vary in proportion but maintain a uniform general morphology. It has no mitosis or necrosis. It is important to highlight the existence of areas of dense collagen, fissures, and pseudoangiomatosis in a significant percentage of FHI, typically positive for CD34, which may simulate other soft tissue tumors and need the use of complementary examinations4,5.

Immunohistochemistry allows the identification of antigens in a particular tissue through the use of spe cific antibodies, which are then visible under the mi croscope due to chemical reactions. The FHI has non specific immunohistochemical characteristics and is similar to other fibroblastic-myofibroblastic tumors14. This component shows positivity for vimentin and smooth muscle actin, being able to show focal CD68 reactivity, desmin and Factor XIIIa6. Mature adipose tissue may show positivity for S100 protein5, whereas primitive mesenchymal tissue is hardly reactive for vimentin, showing occasional focal staining for actin and desmin5. The presence of pseudoangiomatous foci typically CD34 reactive is also described, but they are negative for more specific endothelial markers such as CD31 and podoplanin5. On the other hand, the presen ce of CD34 correlates with well-vascularized tumors15, while Ki-67 shows variable reactivity in the immature mesenchymal component and pseudoangiomatous5.

The FISH technique is a cytogenetic study that allows the evaluation of chromosomes through fluo rescence emission. In our case, given the histological similarity with congenital dermatofibrosarcoma protuberans, FISH was requested for PDGF beta-receptor, which reinforced the diagnosis of FHI, as well as in the literature5. In addition, the study was complemented with FISH for ETV6 present in infantile fibrosarcoma, which was also negative.

The use of nuclear magnetic resonance as a com plementary diagnostic element has recently been reported, showing an organized fat-like structure with heterogeneous soft tissue interleave bands16.

The differential diagnosis depends on the domi nant tissue component, which includes benign tumors such as lipomas, neurofibromas, dermatofibromas, lymphadenopathies, and vascular malformations, as well as malignant tumors such as lymphomas or sar comas.

The treatment of choice is a surgical removal, although sometimes it is not possible due to cosmetic and/or functional implications. A recurrence rate of approximately 15% has been reported secondary to in complete resections6. Although it does not remit spon taneously, there are no cases of malignancy described4.

Conclusions

As physicians, it is important to consider FHI within the differential clinical and histological diag nosis of childhood subcutaneous tumors, especially in patients under two years of age and those located in the armpit, the back, and the upper extremities.

Although its behavior is benign, its location, size, and similarity with malignant lesions generate anxiety in the family group, which makes it necessary to main tain a good therapeutic link, always highlighting the need for histological, immunohistochemical, and mo lecular biological studies to differentiate it from other entities.

Despite the fact that surgical extirpation is the treatment of choice, we must consider the functional and/or cosmetic implications involved, which may require a therapeutic approach along with surgeons, pediatricians, and dermatopathologists, which was our case.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed according to the Declaration of Helsinki and the World Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regulations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.

Referencias:

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Received: May 07, 2018; Accepted: July 15, 2018

Correspondence: Roberto Bustos Macaya. E-mail: robertobustos@med.uchile.cl.

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