Version July 2025
INTRODUCTION —
A variety of cutaneous and subcutaneous nodules may be detected in the newborn. Most are benign and self-limited, such as cysts, subcutaneous fat necrosis, and certain soft tissue tumors. However, some may be locally aggressive or malignant or can be a marker for other abnormalities, such as neural tube defects [1].
Cysts and tumors that present at birth or in early infancy are reviewed here. Other benign skin lesions, vesiculopustular and bullous disorders, and vascular and pigmented lesions in the newborn are discussed separately.
●(See "Skin lesions in the newborn and infant".)
●(See "Vesicular, pustular, and bullous lesions in the newborn and infant".)
●(See "Vascular lesions in the newborn".)
●(See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
●(See "Congenital melanocytic nevi".)
●(See "Subcutaneous fat necrosis of the newborn".)
INITIAL EVALUATION —
The approach to the diagnosis of an infant presenting with cutaneous nodules is illustrated in the algorithm (algorithm 1).
Medical and lesion history — Clinicians should ask parents/caregivers of infants presenting with cutaneous nodules for a complete medical history, including prenatal history, birth history, and a lesion history. Important aspects of a lesion's history include duration, growth, any fluctuations in size or changes in color, texture, consistency, and associated symptoms (including perceived tenderness). A relevant review of systems should also be obtained.
Physical examination — When examining the nodule or mass, it is important to note the location of the lesion (with special attention to midline lesions), whether it is solitary or multifocal, the consistency/firmness of the lesion, size, and the presence of any associated findings (eg, dimples, hairs, color changes).
In addition to examining the presenting lesion, clinicians should perform a complete skin examination for all infants presenting with a nodule or mass, as subtle skin findings could aid in diagnosis.
Imaging studies and biopsy — Imaging evaluation with ultrasound or magnetic resonance imaging (MRI) is appropriate for benign midline lesions (eg, dermoid cysts, thyroglossal cysts) to exclude associated anomalies. (See "Cutaneous developmental anomalies in the newborn and infant", section on 'Midline anterior neck inclusion cyst' and "Cutaneous developmental anomalies in the newborn and infant", section on 'Thyroglossal duct cysts'.)
If the etiology of a nodule is not clinically apparent, further diagnostic testing may be necessary.
●For small, superficial lesions, a biopsy for tissue diagnosis may be the best next step. For larger or deeper nodules or those that might have a deeper connection, we would recommend imaging first, usually with ultrasound. MRI may be the best initial diagnostic test in a minority of cases. (See 'Infantile myofibromatosis' below.)
●If the diagnosis is still in question, fine needle aspiration and core biopsy can be helpful for larger, deeper lesions. Each of these diagnostic modalities has limitations, and in cases where malignancy is suspected, incisional or excisional biopsy may be necessary.
WHEN TO REFER —
The decision of whether to refer an infant presenting with a mass or nodule should depend on the clinician's level of certainty with the diagnosis. Though most lesions are benign and can reasonably be monitored, some lesions (eg, developmental cysts) carry the risk of associated complications, and locally aggressive or malignant neoplasms do rarely occur. A definitive diagnosis may require imaging and/or tissue sampling. Therefore, it is important that the evaluating clinicians feel confident in their assessment so that the appropriate evaluation and treatment are pursued.
General indications for referral include:
●Signs of infection
●Draining lesion
●Impingement on a critical structure
●Risk for functional impairment
●Signs of malignancy
In a retrospective review of superficial lumps in children, signs of malignancy included [2]:
●Onset in neonatal period
●Rapid or progressive growth
●Skin ulceration
●Fixation to/location deep to fascia
●Firm texture and size greater than 3 cm
Infants with any of these features should be referred for further evaluation.
CYSTS —
Common types of cysts include dermoid cysts and epidermoid cysts. Other types, such as branchial cleft cysts or thyroglossal duct cysts, may also occur. (See "Cutaneous developmental anomalies in the newborn and infant".)
Dermoid cysts and sinuses — Dermoid cysts are congenital subcutaneous lesions that are usually distributed along embryonic fusion lines of the facial processes or within the neural axis [3].
●Time of presentation – Dermoid cysts are almost always present at birth, although subtle lesions may be noticed later (eg, when trauma causes inflammation) (picture 1). They present as slow-growing, asymptomatic, rubbery subcutaneous nodules 1 to 4 cm in diameter that are usually solitary. They are nonpulsatile, noncompressible, nontender masses that appear skin colored or bluish [3]. The skin overlying the cyst appears normal unless a pit or a sinus is present [4].
●Cyst location – The head is the most common location. Lesions are frequently found on the anterior fontanelle, bregma (junction of the coronal and sagittal sutures), upper lateral region of the forehead, lateral upper eyelid (picture 2), and submental and occipital regions. However, lesions can occur anywhere on the scalp, face, spinal axis, or other body sites [4].
●Sinuses – Dermal sinus tracts may connect dermoid cysts to the skin surface or to underlying structures, such as the bone, central nervous system (CNS), or paranasal sinuses. Cutaneous sinuses are 1 to 5 mm in length and may have a small tuft of hair protruding from the orifice [3]. Connections to the CNS are most frequent with midline or nasal dermoid cysts, occurring in approximately 25 percent of cases. There are rare reports of lateral dermoid cysts with intracranial connections [5,6]. A pit or sinus is associated with approximately one-half of nasal dermoid cysts. Midline lesions, most commonly in the lumbosacral region, are often markers of spinal dysraphism, including a tethered cord [7,8].
●Pathology – Characteristic histologic findings include a lining of epidermis and evidence of adnexal structures, such as hair follicles, sebaceous glands, and eccrine and apocrine sweat apparatus. Foci of keratinization and, sometimes, mesodermal skin components may be present. These features distinguish dermoid cysts from epidermoid cysts. The latter typically appear later in life on the trunk and extremities. They generally are intradermal and do not uniformly contain hair follicles and sebaceous glands.
●Evaluation and diagnosis – Patients with midline lesions should be evaluated with neuroimaging (MRI) to detect CNS connections or underlying spinal dysraphism [4,9]. In one series of 105 midline craniofacial dermoid cysts, 29 (28 percent) had intracranial extension [9]. Patients with findings on neuroimaging or other clinical abnormalities should be referred to neurosurgery.
Sinus tracts to the skin are usually detected when they become infected and drain purulent material. If the sinus or cyst communicates with the CNS, cerebrospinal fluid may drain from the lesion. This connection also allows the entry of bacteria and may be detected in a patient presenting with meningitis caused by unusual organisms [10].
●Management – Dermoid cysts should be surgically excised because of the risk of associated complications. The timing of excision depends on the site and any associated findings.
The most common complication is infection, including meningitis in lesions that connect to the CNS. In addition, the cysts may adhere to the periosteum or erode the underlying skull [4,11-14]. Nasal dermoids typically enlarge, resulting in damage to the nasal bones. Malignant transformation can occur but is rare.
Thyroglossal duct cysts — Thyroglossal duct cysts are the most common form of congenital neck mass. They represent epithelial remnants of the thyroglossal tract and present characteristically as a midline mass at the level of the thyrohyoid membrane, closely associated with the hyoid bone (picture 3).
Ultrasound examination is an appropriate imaging technique for initial evaluation. Affected children should be referred for surgical excision of the cyst if there is infection or persistent drainage. If the size of the lesion and thyroid function are not problems, they can be followed clinically. (See "Cutaneous developmental anomalies in the newborn and infant", section on 'Thyroglossal duct cysts' and "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid".)
Branchial cleft cysts — Branchial cleft cysts usually arise from the first and second branchial arches. They are commonly located anterior to the sternocleidomastoid muscle on the lower third of the lateral neck (picture 4) or just below the head of the clavicle. The cysts often contain lymphoid tissue. (See "Differential diagnosis of a neck mass", section on 'Branchial cleft cyst'.)
Epidermoid cysts — Epidermoid cysts can arise from occluded pilosebaceous units, by entrapment of epidermal cells along embryonic lines of closures, or traumatic displacement of epidermal cells into the dermis. They usually develop after puberty, although some present in the newborn period [15]. Their histologic appearance may be similar to dermoid cysts, or they may contain stratified squamous epithelium.
Examples in newborns include milia, median raphe cysts, and midline anterior neck inclusion cysts [16]. In most cases, epidermoid cysts in newborns can be monitored clinically, as they are asymptomatic and unlikely to lead to complications. (See "Skin lesions in the newborn and infant", section on 'Milia' and "Skin lesions in the newborn and infant", section on 'Median raphe cysts' and "Cutaneous developmental anomalies in the newborn and infant", section on 'Midline anterior neck inclusion cyst'.)
SUBCUTANEOUS FAT NECROSIS —
Subcutaneous fat necrosis of the newborn is a rare self-limited panniculitis that affects newborns in the first few weeks of life [17]. It typically affects term or post-term newborns and usually follows perinatal complications, such as birth asphyxia, hypothermia, meconium aspiration syndrome, newborn failure to thrive, forceps delivery, and maternal high blood pressure and/or diabetes [18-20].
Subcutaneous fat necrosis of the newborn presents with multiple firm, nontender subcutaneous nodules or large plaques that appear one to four weeks after birth. Commonly affected sites are the cheeks, buttocks, back, and limbs; the overlying skin may be erythematous (picture 5 and picture 6).
Subcutaneous fat necrosis of the newborn is discussed in detail separately. (See "Subcutaneous fat necrosis of the newborn".)
BENIGN TUMORS —
Most soft tissue tumors in newborns and infants are benign [21]. These include hemangiomas and other vascular tumors, fibromatoses, non-Langerhans cell histiocytosis, and cutaneous mastocytosis.
Vascular tumors — Vascular tumors occurring in neonates and infants, including infantile hemangiomas, congenital hemangiomas, tufted angiomas and kaposiform hemangioendotheliomas, and pyogenic granulomas, are discussed separately.
●(See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
●(See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)
●(See "Pyogenic granuloma (lobular capillary hemangioma)".)
Infantile myofibromatosis — Infantile myofibromatosis, formerly known as congenital fibromatosis, is the most common fibrous tumor of infancy [22]. In three case series, approximately 60 percent of cases were congenital, and 90 percent were detected during the first year of life [23-25]. Infantile myofibromas occur more commonly in male children (60 percent) [25]. In most cases, these tumors are sporadic, but rare familial cases have been described. Both autosomal recessive and autosomal dominant inheritance patterns have been reported [26-28].
Genetics — Variants in the PDGFRB gene, which encodes the platelet-derived growth factor receptor-beta, have been identified as the cause of most cases of autosomal dominant infantile myofibromatosis [29-31]. Penetrance may be variable [32]. PDGFRB variants have also been identified in cases of sporadic infantile myofibromatosis [33,34]. Gain-of-function variants of PDGFRB may be associated with multiple disorders and complex syndromes, including Kosaki overgrowth syndrome (MIM #616592) and premature aging syndrome type Penttinen (MIM #601812) [35]. Somatic gain-of-function variants in PDGFRB have been identified in fusiform cerebral aneurysms [36-38].
Variants in NOTCH3 (the human homolog of the Drosophila melanogaster type I membrane protein Notch3) and in SRF (serum response factor) have also been reported in cases of infantile myofibromatosis, suggesting genetic heterogeneity [39,40].
Clinical subtypes — Infantile myofibromatosis occurs in three forms:
●Solitary – In the solitary myofibromatosis (the most frequent type), a single lesion affecting the skin or muscle is present, most commonly on the head, neck, or trunk (picture 7A and picture 7B).
●Multicentric – In the multicentric form, which is more likely to be congenital, multiple lesions are present and may affect muscles, bones, skin, and subcutaneous tissues (picture 8) [24,25,41].
●Generalized – The generalized form is characterized by visceral involvement in addition to skin lesions and is associated with a poor prognosis. The most common sites of visceral involvement are lung, bone, gastrointestinal tract, heart, and liver [42].
Clinical presentation — The superficial lesions of infantile myofibromatosis are rubbery, firm, rounded nodules that may be mobile [43]. The deeper lesions are fixed. They range in diameter from 1 to 7 cm [24]. In some cases, the overlying skin has a red or purple discoloration that may mimic a hemangioma (picture 8) [43]. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
The lesions may also be sclerodermoid [25]. Reticulate vascular patches with underlying atrophy have rarely been described and are more common in the multicentric form [25,44]. Skin lesions associated with the generalized form vary; rare cases of atrophic papules and widespread, hypopigmented macules have been reported [45].
Diagnosis — The diagnosis of infantile myofibromatosis is made based on clinical features (see 'Clinical presentation' above), characteristic histopathology, and genetic analysis.
●Pathology – The histologic appearance is similar in solitary and multiple cutaneous and visceral lesions [46]. There are well-circumscribed masses of spindle-shaped cells staining as fibroblasts or smooth muscle cells, bland necrosis with stippled calcification, and plentiful thin-walled vessels. Atypia is uniformly absent.
●Imaging studies for visceral involvement – In patients with multicentric or generalized disease, additional evaluation to exclude visceral involvement should be performed. While there are no established guidelines for staging or surveillance, some authors recommend screening all patients (even those with apparent solitary disease) for visceral involvement [31,47,48]. In a review of published cases of solitary infantile myofibromatosis, 9 percent had internal involvement [49].
Radiograph/bone scans, ultrasound, echocardiography, computed tomography (CT), fluorodeoxyglucose-positron emission tomography (FDG-PET), and MRI have all been used effectively to screen for systemic disease [25,48,50,51]. However, whole-body MRI has gained popularity due to its superior soft tissue resolution [52]. One group suggests a dedicated MRI to delineate the clinically apparent lesion and a rapid whole-body MRI at diagnosis followed by imaging surveillance every three to six months for two years [48].
Genetic testing – Tumor tissue should be sequenced for PDGFRB variants, and additional genetic evaluation may be indicated [31]. All patients should be referred for genetic counseling [31]. This has implications not only for the patient but also for family members, as first-degree relatives of patients diagnosed with infantile myofibromatosis or PDGFRB germline variants should also undergo surveillance [31].
Due to the association of cerebral aneurysms with PDGFRB variants, a screening brain MRI at age 15 to 18 years can be considered for patients with germline PDGFRB variants.
Treatment and prognosis
●Solitary lesions – Solitary lesions are often surgically excised. However, close observation of these tumors may be appropriate in cases without visceral involvement, as most lesions spontaneously involute in one to two years, occasionally leaving residual calcifications or atrophic scars [24,25,41,43].
●Patients with visceral involvement – Patients with visceral involvement must be followed closely due to the higher risk of morbidity and mortality. Progressive visceral myofibromas or tumors that affect function or cause local complications due to mass effect can be surgically excised or treated with chemotherapy [42,52-54] or PDGFR-beta tyrosine kinase inhibitors (eg, imatinib) [35,55-59].
●Follow-up and prognosis – Recurrence of infantile myofibromatosis is unusual but can be delayed into adulthood [32]. Therefore, long-term follow-up is indicated for patients with the multicentric or generalized forms of myofibromatosis [48]. Recurrences can be managed by re-excision or treated with chemotherapy [60].
Though the prognosis is generally excellent, infantile myofibromatosis can rarely be progressive and fatal [47]. Poor outcomes are more frequent among infants with the generalized form and extensive visceral involvement, often due to cardiopulmonary or gastrointestinal complications.
Plaque-like myofibroblastic tumor — Plaque-like myofibroblastic tumor, first described in 2007, is a rare benign soft tissue tumor presenting in infants and young children as a firm, irregularly shaped dermal plaque typically located on the middle or lower back, although they can develop in other areas, such as the hips or thighs (picture 9) [61-64]. Lesions are 2 to 8 cm in diameter and reddish to brown in color.
The diagnosis is based on the clinical presentation and a skin biopsy. Histologically, the tumor resembles a dermatofibroma, with a relatively well-circumscribed proliferation of spindle cells arranged in short fascicles with thin collagen bundles extending through the entire reticular dermis [61]. On immunohistochemistry, these lesions stain for factor XIIIa and smooth muscle actin but are CD34 negative, consistent with a myofibroblastic lineage.
The differential diagnosis of plaque-like myofibroblastic tumor includes other dermal tumors, including clustered dermatofibroma, fibrous connective tissue nevus, dermatomyofibroma, and dermatofibroma protuberans (table 1) [65,66]. (See "Skin lesions in the newborn and infant", section on 'Connective tissue nevus' and "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging" and "Overview of benign lesions of the skin".)
Treatment is surgical excision. Local recurrence has been reported [61,67].
Infantile digital fibromatosis — Infantile digital fibroma, also called recurrent digital fibrous tumor of childhood, is a rare benign childhood tumor that occurs almost exclusively on the digits [68,69]. It usually develops in the first year of life and typically presents as a firm, reddish-pink or skin-colored, asymptomatic nodule 3 to 35 mm in size located on the dorsolateral aspects of the fingers and toes, characteristically sparing the thumbs and great toes (picture 10) [68]. Tumors may be multiple (picture 11) and, if large, may cause deformity and functional impairment.
The diagnosis is based on the clinical appearance of the lesion in many cases. If performed, a biopsy shows a dermal nonencapsulated proliferation of spindle-shaped myofibroblasts intertwined with coarse collagen fibers, with perpendicular cell fascicles reaching the epidermis. The presence of eosinophilic intracytoplasmic inclusions that stain red with Masson trichrome is pathognomonic. On immunohistochemistry, tumors consistently express alpha-smooth muscle actin, calponin, and desmin [68].
Because lesions may regress spontaneously over several months to years, observation is a reasonable first-line management strategy [70,71]. Lesions causing functional impairment may require surgical excision to prevent joint deformities. However, rapid recurrence after surgical excision is common [68,69]. Mohs micrographic surgery has been successfully used in a few cases [72,73].
Other juvenile fibromatoses — Other rare fibromatoses that occur in infancy include infantile desmoid-type fibromatosis, fibromatosis colli (congenital torticollis), fibrous hamartoma of infancy, lipofibromatosis, precalcaneal congenital fibrolipomatous hamartoma, gingival fibromatosis, juvenile hyaline fibromatosis, and infantile systemic fibromatosis [74-80]. (See "Congenital muscular torticollis: Clinical features and diagnosis" and "Soft tissue lesions of the oral cavity in children", section on 'Gingival overgrowth'.)
Juvenile xanthogranuloma — Juvenile xanthogranuloma is a rare benign histiocytic proliferative disorder of dermal dendrocyte origin and is the most common of the non-Langerhans cell histiocytoses. It typically presents within the first two years of life and, though less common, may be congenital [81]. The most common presentation of juvenile xanthogranuloma is a firm, well-circumscribed, yellow-red tumor that increases in size over the first few months of life (picture 12). Less common presentations include exophytic tumors, agminated lesions over an erythematous patch or plaque, infiltrative plaques, subcutaneous masses, or multiple lesions (picture 13). The most common extracutaneous sites of involvement are the eyes, followed by the liver, bone marrow, and lung [81]. Juvenile xanthogranuloma is relatively common among children with neurofibromatosis type I [82] and may also be associated with Noonan syndrome [83], a related RASopathy.
The clinical presentation, diagnosis, and management of juvenile xanthogranuloma are discussed in greater detail separately. (See "Juvenile xanthogranuloma (JXG)".)
Cutaneous mastocytosis — Cutaneous mastocytomas are rare lesions composed of mast cells that occur in infancy and childhood (picture 14 and picture 15). They may be solitary or multiple. Manipulation of the lesion by rubbing or pressure may trigger mast cell mediator release with resultant flushing and, occasionally, hypotension (referred to as Darier sign). In most cases, caregivers have noticed this phenomenon and can describe it without the need to disturb the lesion and induce symptoms. Cutaneous mastocytomas typically regress spontaneously by adolescence. Cutaneous and systemic mastocytosis are discussed separately. (See "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis".)
MALIGNANT TUMORS —
Malignant soft tissue tumors that present at birth or in the neonatal period are rare, and over 50 percent present in the skin or subcutaneous tissue [84]. However, malignant soft tissue tumors occur more frequently in children than in adults, representing approximately 7 percent of all pediatric cancers [84].
Examples include rhabdomyosarcoma, infantile fibrosarcoma, neuroblastoma, and congenital leukemia [85]. Infantile fibrosarcoma and malignant rhabdoid tumors appear most commonly in the first year of life [84].
Infantile fibrosarcoma — Infantile fibrosarcoma, also called congenital fibrosarcoma, is a spindle cell tumor of the soft tissues and the second most common type of soft tissue sarcoma in infants. Most infantile fibrosarcomas are diagnosed in the first year of life [86].
Clinical presentation — In most cases, infantile fibrosarcoma presents as localized, rapidly growing masses most frequently involving the distal extremities, followed by the trunk and the head and neck region [21,86-88].
Diagnosis — A biopsy of the tumor tissue is necessary for the diagnosis.
●Histopathology – Histologically, infantile fibrosarcoma is characterized by spindle cells arranged in interlacing fascicles with a high mitotic rate and positive staining for vimentin.
●Genetics – The majority of infantile fibrosarcomas have a recurrent translocation t(12;15)(p13;q25) that results in a fusion gene involving the neurotrophic tyrosine receptor kinase 3 (NTRK3) gene, called ETV6::NTRK3 (also known as Tel-TRKC) [89-94]. This structural rearrangement results in a tropomyosin receptor kinase (TRK) fusion oncoprotein that drives uninterrupted downstream signaling messages, oncogenic transformation, and tumor growth [95-97]. Immunohistochemical methods are available to identify TRK fusions in infantile fibrosarcoma and can help to differentiate infantile fibrosarcoma from other pediatric fibromatous tumors [98-100].
The accurate and timely identification of TRK fusions is of immediate therapeutic importance given that TRK inhibitors have been shown to have robust and durable activity in TRK fusion-positive solid tumors, such as infantile fibrosarcoma. (See "TRK fusion-positive cancers and TRK inhibitor therapy", section on 'Testing approach'.)
TRK fusions involving the NTRK1, NTRK2, and NTRK3 genes have been identified in a variety of other pediatric mesenchymal tumors but at a lower frequency than in infantile fibrosarcoma [101,102]. (See "TRK fusion-positive cancers and TRK inhibitor therapy", section on 'Prevalence' and "TRK fusion-positive cancers and TRK inhibitor therapy", section on 'Normal and tumor biology'.)
Management — Surgical resection is the mainstay of treatment. However, because in many cases the tumor is locally infiltrative and not amenable to complete surgical resection, preoperative (neoadjuvant) chemotherapy is frequently used to allow more conservative tissue-sparing surgery [86,92,103].
Neoadjuvant larotrectinib has been successfully used for infantile fibrosarcoma [104-107]. Larotrectinib, an oral small molecule TRK inhibitor, is approved in the United States and elsewhere for adults and children (ages 28 days to 82 years) with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity, and that have no satisfactory alternative treatments or have progressed following treatment. (See "TRK fusion-positive cancers and TRK inhibitor therapy", section on 'Efficacy of TRK inhibitors in TRK TKI-naïve patients'.)
In a retrospective observational study of pediatric patients with locally advanced or metastatic infantile fibrosarcoma, larotrectinib reduced the need for subsequent therapies, such as mutilating surgeries, radiation, and additional chemotherapy, compared with the standard of care chemotherapy-based group [107]. Adverse effects of larotrectinib include low-grade increases in liver enzyme levels, decrease in neutrophil count, anemia, and vomiting [105].
Prognosis — Although locally infiltrative, infantile fibrosarcoma rarely metastasizes and generally has a good prognosis; more than 80 percent are cured [108-110]. However, bleeding and coagulopathy may be life-threatening complications [111].
Rhabdomyosarcoma — Rhabdomyosarcoma is a highly malignant skeletal muscle neoplasm that arises from embryonal mesenchyme. It is the most common soft tissue sarcoma in infants, accounting for one-third to one-half of all cases [87,112]. The primary cutaneous form typically presents as a single firm subcutaneous nodule that adheres to the skin above and tissue underneath [43]. The overlying skin may be erythematous or shiny, occasionally mimicking a deep hemangioma [113]. An extremely rare neonatal presentation is alveolar rhabdomyosarcoma, a very aggressive tumor that frequently includes multiple skin and subcutaneous metastases [114,115]. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)
Other soft tissue sarcomas — Other soft tissue sarcomas occurring in the first year of life include the Ewing sarcoma family of tumors, malignant rhabdoid tumors, hemangiopericytoma, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and malignant peripheral nerve sheath tumor [85,87,112]. (See "Clinical presentation, staging, and prognostic factors of Ewing sarcoma" and "Dermatofibrosarcoma protuberans: Epidemiology, pathogenesis, clinical presentation, diagnosis, and staging".)
Neuroblastoma — Neuroblastoma, the most common malignancy identified at birth, typically presents with an abdominal mass. Metastatic cutaneous lesions are present in approximately one-third of children with congenital neuroblastoma [43]. In one review of 208 neonates with cutaneous metastases, 17 percent were neuroblastoma metastases [116].
Lesions appear as firm, nontender, bluish-red nodules and papules distributed over the entire body ("blueberry muffin baby") and have a distinctive response to rubbing, characterized by central blanching with a surrounding halo of erythema that persists for 30 to 60 minutes [43,117]. The mechanism is thought to be vasoconstriction induced by catecholamine release [118]. (See "Epidemiology, pathogenesis, and pathology of neuroblastoma" and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)
Congenital leukemia — Congenital leukemia is an extremely rare disorder that typically presents at birth with hepatosplenomegaly, lymphadenopathy, central nervous system (CNS) involvement, petechiae, and ecchymoses [119]. Many affected patients have red/brown or violaceous nodules caused by infiltration of the skin by leukemic cells (known as leukemia cutis) (picture 16) [119,120]. The differential diagnosis of this so-called "blueberry muffin baby" appearance includes intrauterine infections, hemolytic diseases, and other tumors.
Rarely, affected infants present with a vesiculopustular eruption [121] or with a solitary soft tissue mass (so-called myeloid sarcoma) [122]. The diagnosis is confirmed by skin biopsy. The prognosis depends on the presence of the associated systemic leukemia [119,123]. Patients with aleukemic leukemia cutis can be managed conservatively, though they should be monitored closely for progression.
Congenital self-healing reticulohistiocytosis — Congenital self-healing reticulohistiocytosis (CSHR; Hashimoto-Pritzker disease, also called congenital self-healing Langerhans cell histiocytosis) is a skin-limited variant of Langerhans cell histiocytosis that regresses spontaneously in weeks to months. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis".)
CSHR is an uncommon disease. However, its incidence is likely underestimated because of the high rate of spontaneous resolution and lack of clinical recognition [124].
●Genetics – While mutations in the mitogen-activated protein (MAP) kinase cell-signaling pathway, commonly including BRAF V600E, are well described in Langerhans cell histiocytosis, these genetic alterations are rare in CSHR [125]. Few reports have identified BRAF V600E mutations in lesional skin [126], although most published cases describe negative testing for BRAF mutations in congenital solitary lesions [125]. Mutations in HRAS and PTEN have also been rarely described in CSHR [125,126]. Circulating mononuclear cells with the BRAF V600E mutation are infrequently found in patients with CSHR, whereas they can be identified in the majority of patients with multifocal skin and multisystem Langerhans cell histiocytosis [127,128].
●Clinical presentation – CSHR presents at birth or in the newborn period as solitary (25 percent of cases) or multiple cutaneous nodules that may be located anywhere on the body (picture 17 and picture 18) [129]. The uninodular form (picture 19) has also been termed solitary Langerhans cell histiocytoma, solitary congenital self-healing reticulohistiocytoma, histiocytoma, or indeterminate cell histiocytoma [126]. The nodules often centrally ulcerate either before or shortly after birth (picture 20). Vesicles, bullae, and so-called "blueberry muffin presentations" also have been reported [130-132].
All lesions heal within a few months, sometimes leaving an atrophic, white scar.
●Diagnosis – The diagnosis of CSHR is based on the histopathologic evaluation of a skin biopsy. Histology shows a proliferation of mononuclear cells resembling Langerhans cells with characteristic abundant eosinophilic cytoplasm and a lobulated, kidney-shaped nucleus. Immunostaining is positive for CD1a, CD4, CD207, and S-100 protein. Staining for E-cadherin, Ki-67, and phosphorylated histone H3 is not helpful in differentiating CSHR from disseminated Langerhans cell histiocytosis with cutaneous involvement [124]. Characteristic features seen on electron microscopy are dense bodies, regularly laminated bodies, and Birbeck granules. Genetic evaluation of lesional tissue and/or circulating cells should be considered.
●Evaluation for systemic involvement – All infants with cutaneous lesions of Langerhans cell histiocytosis should be evaluated for systemic involvement. Evaluation includes a complete blood count, coagulation studies, serum chemistries, liver function tests, urine osmolality, chest and bone radiographs, abdominal ultrasound, and bone marrow biopsy if necessary [133]. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis".)
A review of 82 published cases suggested that the morphology of a solitary congenital nodule in a neonate portends a favorable prognosis, without risk of systemic disease [134]. Further studies are needed before clinicians can confidently advise against evaluation for systemic involvement, however.
●Management – No treatment is required for CSHR. However, close clinical and laboratory monitoring is important because of the possibility of recurrence or progression [135]. A review of 126 reported cases of CSHR found a recurrence rate of 10 percent (all within the first year of life) and a mortality rate of 3 percent [136]. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis".)
SUMMARY AND RECOMMENDATIONS
●Evaluation of the infant presenting with a nodular lesion – The evaluation of an infant with a nodule involves a thorough history and complete physical examination with attention to lesional history (onset, growth trajectory, associated symptoms). Signs associated with malignancy, lack of diagnostic certainty, and potential for association with other structural anomalies (midline lesions, developmental hotspot) warrant prompt referral or additional diagnostic work-up with imaging and/or tissue sampling. (See 'Initial evaluation' above.)
●Cysts – Common types of cysts include dermoid cysts, thyroglossal duct cysts, branchial cleft cysts, and epidermoid cysts. Dermoid cysts are small (1 to 4 cm in diameter), usually solitary, slow-growing, asymptomatic, rubbery, nontender masses that appear skin colored or blue. The skin overlying the cyst appears normal unless a pit or a sinus is present (picture 2). They are commonly located over the anterior fontanelle, junction of the coronal and sagittal sutures, upper lateral region of the forehead, lateral upper eyelid, and submental region. Midline lesions require imaging given the high risk of central nervous system (CNS) connection or spinal dysraphism. (See 'Cysts' above.)
●Subcutaneous fat necrosis – Subcutaneous fat necrosis is a rare condition that typically affects term or post-term newborns in the first few weeks of life, usually following perinatal complications. It is characterized by multiple firm, nontender subcutaneous nodules or large plaques over bony prominences (eg, cheeks, buttocks, back, limbs) (picture 6). Subcutaneous fat necrosis of the newborn is discussed in detail separately. (See "Subcutaneous fat necrosis of the newborn".)
●Benign tumors – Most soft tissue tumors in newborns and infants are benign. These include hemangiomas and other vascular tumors, fibromatoses, non-Langerhans cell histiocytoses, and cutaneous mastocytosis. (See 'Benign tumors' above.)
•Vascular tumors – Vascular tumors occurring in neonates and infants, including infantile hemangiomas, congenital hemangiomas, tufted angiomas and kaposiform hemangioendotheliomas, and pyogenic granulomas, are discussed separately. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)" and "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)" and "Pyogenic granuloma (lobular capillary hemangioma)".)
•Infantile myofibromatosis – Infantile myofibromatosis, also known as congenital fibromatosis, is the most common fibrous tumor of infancy. It presents in most cases as a solitary lesion on the head, neck, or trunk (picture 7A-B) but can be multicentric or generalized. The diagnosis is based on a lesion biopsy. (See 'Infantile myofibromatosis' above.)
●Malignant tumors – Malignant tumors affecting the skin and soft tissues of newborns and infants include infantile fibrosarcoma, rhabdomyosarcoma, neuroblastoma, congenital leukemia, and congenital self-healing reticulohistiocytosis (CSHR). (See 'Malignant tumors' above.)
•Infantile fibrosarcoma – Infantile fibrosarcoma is the second most common type of soft tissue sarcoma in infants. It presents as a rapidly growing, poorly circumscribed subcutaneous mass most frequently located on the distal extremities. Although locally infiltrative, these tumors rarely metastasize; however, bleeding and coagulopathy may be life-threatening complications. Evaluation for tropomyosin receptor kinase (TRK) fusions, which are common in infantile fibrosarcoma, is important and can guide management. Larotrectinib, a TRK inhibitor approved for the treatment of neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors in children and adults, has shown promise as neoadjuvant and adjuvant treatment of infantile fibrosarcoma. (See 'Infantile fibrosarcoma' above and "TRK fusion-positive cancers and TRK inhibitor therapy".)
•Rhabdomyosarcoma – Rhabdomyosarcoma is a highly malignant skeletal muscle neoplasm and the most common soft tissue sarcoma in infants. The primary cutaneous form typically presents as a single firm subcutaneous nodule that adheres to the skin above and tissue underneath. (See "Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging".)
ACKNOWLEDGMENT —
The UpToDate editorial staff acknowledges Josie A Pielop, MD, who contributed to an earlier version of this topic review.
