Teaching Case

21-year-old female patient with exacerbated chronic abdominal pain in right hypochondrium and lower back. She presented multiple cutaneous “cafe au lait” spots (>5) and axillary freckling (Fig. 1). In abdomen a stony mass and a Giordano sign were present.
She referred that two brothers died due to complications of schwannomas.

Abdominal IV contrast CT showed an oval retroperitoneal mass, well delimited, of 16 cm, predominantly hypodense with heterogeneous enhancement and hypodense necrotic areas, that displaced the ascending colon and right kidney without infiltrating them (Fig. 2). Given that it may be difficult to differentiate MPNST from plexiform neurofibromas based on image, and as part of treatment, surgical resection was performed. The histopathological diagnosis of a low-grade malignant peripheral nerve sheath tumour (MPNST) was made.
Incidentally an exophytic tumour in the nipple-areola complex of the left breast was seen on CT, that was dark brown at inspection; at ultrasound it appeared as an oval dermal lesion with lobed borders, hypoechoic and no flow (Fig. 3 and Fig. 4). Complementary mammography projection of left breast showed a multilobulated and isodense mass in the topography of the nipple, the mammary parenchyma had no lesions. (Fig. 5)

Background
Neurofibromatosis is a phakomatosis (neurocutaneous syndrome) that involves tissues originated from embryonic ectoderm (central nervous system, skin and eyes) [1, 2]; in neurofibromatosis type 1 (NF1, von Recklinghausen disease), the alteration lies in the long arm of chromosome 17 where neurofibromin (a tumour-suppressing protein) is coded, with its function being diminished or absent [1, 5].

Clinical perspective
NF1 has an inherited autosomal dominant pattern, and its diagnosis is based on clinical criteria established by the National Institutes of Health Consensus Development Conference, with at least two of them required to make the diagnosis [2, 5, 7]; features are summarised in Fig. 6. The patient met several criteria: “cafe au lait” spots, axillary freckling, retroperitoneal MPNST, breast lesions and family history.

NF1 is the most frequent phakomatosis, affecting multiple systems with masses in subcutaneous tissue (including breast), that can become expansive and infiltrative (plexiform type) [2, 5]. Skin lesions may grow to become nodular, hyperpigmented and pedunculated [1, 7]. The risk of malignant transformation varies, being low for neurofibroma and greater for the plexiform type [1, 3]. Because of its high penetrance, all relatives of patients with NF1 should undergo screening tests [7].

Once diagnosis is considered, referral should be made to clinicians experienced in NF1, the basis of management being monitoring of manifestations and patient education [6, 7].

Imaging perspective
Breast lesions mammographically appear as well-defined peri-areolar masses, often multiple, borders may be surrounded by air density reflecting their superficial nature; the skin lesions can mimic and partially obscure parenchymal lesions [8, 9]. At ultrasound they appear as well-defined hypoechoic mass with posterior acoustic enhancement, located in the subcutaneous tissue similar to fibroadenoma [4, 9].

Neurofibromas of breast are rare manifestations of NF1 and occur on the nipple-areolar complex. [9]. The literature suggests that women with NF1 are at a higher risk of developing breast cancer compared to general population; however, there are not specific considerations for screening in these patients [10]. Surgical removal of cutaneous neurofibromas is indicated if they cause discomfort or are visible and stigmatising [11].

Outcome
There is an 8–13% lifetime risk of developing MPNST in NF1, principally in individuals aged 20–35 years, and are hard to detect, metastasise widely and often have a poor prognosis [7]. Purpose of treatment is removal of lesions with tumour free margins; adjuvant radiotherapy has a role in treating MPNST larger than 5 cm, high grade lesions and incompletely excised tumours [7].

Take home message

Close collaboration between clinicians and radiologist will facilitate diagnosis and management of NF1 and its complications.