Benign benign fibrous histiocytoma (BFH) was first described as a separate clinical entity in the 1960s after a lengthy process aiming towards a precise identification of fibrohistiocytic lesions and the distinction between benign and malignant variants [1]. It is now considered a benign mesenchymal lesion composed of fibroblasts and histiocytes arising in the cutaneous and non-cutaneous soft tissues, although disputes still exist on whether this is a true tumor or a reactive mass at least as for the cutaneous form [2, 3]. Confusion on the nature of fibrohistiocytic lesions also accounts for the variety of names used to describe this tumor and its variants: Dermatofibroma, sclerosing hemangioma, adult xanthogranuloma, fibroxanthoma, and nodular subepidermal fibrosis are some of the terms more commonly used in the past to identify this tumors [1].

While cutaneous BFH (dermatofibroma) usually originates in sun-exposed skin, non-cutaneous soft tissue BFH usually presents itself in subcutaneous tissues of the extremities and more rarely in visceral spaces like the retroperitoneum and pelvis; localizations in tendons are rare and visceral presentations anecdotal [3]. The “deep” soft tissue variant of the tumor seems to be relatively more frequent in young children, especially in the head and neck region [4]. BFH arising in the orbital tissues represents the most frequent primary mesenchymal tumor of the orbit in adult patients and accounts for most of the head and neck localizations that would otherwise be rare [5]. In the ENT practice BFH has been more commonly encountered in the bone and soft tissues of the oral cavity such as in the tongue, gingival or alveolar ridge, mandible, maxilla, lips, soft palate, and floor of the mouth. The nasal cavity and paranasal sinuses, larynx, trachea, temporomandibular joint, and submandibular and parotid glands are more rarely involved [5]. A malignant subtype of fibrous histiocytoma has also been described [2, 3]. Tumors of the nasal vestibule are generally rare and reports of nonepithelial variants absolutely exceptional [6] ; no definite cases of fibrohistiocytic tumors in this site are present in literature so far.

Figure 1. Intraoperatory view of the mass.

In February 2012 a 54 year old Italian male presented in the outpatient ambulatory of the Endoscopic Upper Airways Surgery Unit of the University Hospital of Padua with a large, nontender mass of the right nasal vestibule which he had noticed 3 months earlier and had rapidly grown in size since then. The tumor caused local discomfort and unilateral nasal obstruction. The patient referred no specific personal or professional risk factors for nasal disease apart from persistent nasal picking. In his general history there were no other significant pathologies apart from hypertension under treatment with vasodilators.

Figure 2. Section of the tumor under direct light microscopy (H&E stain x200).

On direct examination the lesion appeared as a pedunculated mass without alterations of the overlying mucosal lining, originating from the alar region of the right nostril (Fig. 1). Complete upper aerodigestive tract endoscopic examination revealed no other lesions.

The tumor was excised in the operating room under local anesthesia ten days later and the specimen was sent for histological examination. The postoperative course was completely uneventful and the patient was dismissed the same day.

Figure 3. Immunohistochemical stain for CD68 (x400).

Microscopic examination revealed an encapsulated submucosal neoplasm composed of spindle-shaped fibroblastic and foamy/vacuolar histiocyte-like cells proliferating in a typical storiform pattern. There were no signs of cytologic atypia and no significant mitotic activity (Fig. 2). Immunochemical examination revealed focally positive reactivity for vimentin and CD68 for both KP1 and PGM1 variants (Fig. 3), whilst immunoreactivity for smooth muscle actin, muscle specific actin (HHF35), CD31, CD34, CD35, MNF116 and MIB1 was negative, putting forward soft tissue BFH as the final diagnosis.

A 30 month clinical follow up revealed no local recurrence, other lesions or associated diseases.

Fibrous histiocytomas are neoplasms of mesenchymal origin composed of a dual cell population of histiocytes and fibroblasts arising in soft-tissue or bone [2].

Dermatofibromas (cutaneous fibrous histiocytomas) usually present as rapidly evolving, yet asymptomatic single, round, oval to targetoid well circumscribed hard papules (more rarely plaques or tumors) and mainly occur on the extremities and trunk; rarely such lesions have been reported on the face. They are quite common (compared to noncutaneous variants) and may develop at any age, but particularly during the third and fourth decades. Multiple tumors are regarded as a marker of immune suppression or autoimmune disease (Sjögren syndrome, pemphigus vulgaris, myasthenia gravis, ulcerative colitis treated with immunosuppressive drugs, transplant recipients or AIDS patients). The etiology has not been established unequivocally. It remains controversial whether it is an inflammatory or neoplastic process [2].

On histological examination dermatofibromas present as ill-defined, predominantly dermal lesions characterized by a variable number of spindle and/or rounded cells. They show a dense infiltrate of spindle-shaped and/or round cells, some of which may be fibrocytes and/or macrophages, centered in the reticular dermis and sometimes, the upper part of the subcutis. Early lesions are rich in macrophages. Lymphocytes often spread throughout the lesion with frequent prominence in the peripheral part, but may be absent in advanced stages. At times foam cells may be prominent in deeper areas adjacent to subcutaneous fat. Dermatofibromas reveal a variable immunohistochemical profile: Early lesions are rich in reactivity for macrophage markers such as PGM1 or KP1 (CD68), but also exhibit strong reactivity for factor XIIIa in both macrophages and fibroblasts. This reactivity is mostly seen at the periphery and continuously diminishes with the ageing of the lesion to be completely absent in atrophic variants [2].

Benign fibrous histiocytoma of bone is a benign lesion composed of spindle-shaped fibroblasts, arranged in a storiform pattern, with a variable admixture of small, multinucleated osteoclast-like giant cells. Foamy cells (xanthoma), chronic inflammatory cells, stromal hemorrhages and hemosiderin pigment are also frequently encountered. It most frequently occurs in the long bones (40% of cases) mainly involving the femur and tibia and pelvic bones (25%), in particular the ilium. However, this tumor may involve virtually any bone including the facial skeleton and skull. In the long bones, benign fibrous histiocytoma is chiefly located in the epiphysis or diaphysis [3].

Benign FH of the non-cutaneous soft tissues most often develops as a painless and slowly enlarging mass, with specific symptoms caused by interference with the normal anatomy and physiology of the area in which it arises. The tumor has often been associated with a previous trauma, sun exposure, and chronic infection, suggesting a possible reactive nature. In the head and neck region differential diagnosis should be made between BFH, solitary fibrous tumor (SFT), and neurofibroma (NF) [5].

Excluding the ocular/periorbital tissues, and the scalp and skull, head and neck involvement by noncutaneous BPH is generally considered as a rarity with few cases reported in both bony structures and soft tissues of the region. Reported cases of deep BPH involved mainly “deep” osseous forms of the mandible and maxilla [7] and true soft tissue variants were predominantly located in the oral and perioral areas [5, 8] although virtually any structure in the ENT district may be involved [1].

Analysis of the English and international literature as present on MEDLINE revealed 12 well-defined cases of soft tissue BPH, mainly involving the internal parts of the nasal cavities, and the maxillary sinus [9-20] (Table 1).

Four less well-definite cases deriving from dated reports were individuated. Doubts on the cases regarded the lack of clarity in the definition of the exact histological characteristics and particularly on the individuation of the benign or malignant nature of the lesion [21-23].

No definite cases involving the nasal vestibule have been identified, so far. One case of a not-better-specified histiocytoma of the nasal vestibule has been reported in 1964 [24]. Despite our efforts it was impossible to access the original document through our institution’s library and allied services. Anyhow, given the amount of time that has passed, there would have been no possibility to re-assess the case using modern criteria. In fact, knowledge over histiocytic lesions at that time was limited, in the absence of a clear-cut definition of this type of neoplasms and an univocally accepted classification of soft tissue tumors in general; thus, even in the presence of a perfectly performed direct microscopic assessment with the instruments available then, an accurate differential diagnosis between BFH and other soft tissue neoplasms should have been extremely difficult especially if one considers the fact that immunohistochemical marking was not available yet. Case 2 presented in the work by Perzin et al. in 1980 [12] refers to a tumor approaching the region of the nasal vestibule but the description and the fact the it was excised through polipectomy indicate that the mass had a tendency to grow towards the interior of the nasal cavity.

In the area of the nose and paranasal sinuses patients with soft tissue BFH usually present no history of pain and the predominant clinical feature of discomfort and/or nasal obstruction from a rapidly enlarging mass. Swelling in the affected area, nasal discharge, epistaxis and loosening of teeth, facial asymmetry and proptosis may be present in some cases. In the presence of CT imaging showing aggressive bone destruction it may be difficult to differentiate these lesions from some malignant lesions located in the sinonasal cavity such as squamous cell carcinoma. The diagnosis of FH is based mainly on histological findings [16]. In the presence of involvement of the more internal part of the nasal cavities and the paranasal sinuses, superimposed sinonasal pathology such as rhinosinusitis with dense secretions and mucocele may originally mask the underlying condition [17, 20].

No specific risk factors for BFH of the nasal fossa have been identified in literature, but given the probable reactive nature of soft tissue BFH in general, persistent nasal picking and consequent irritation of the vestibular area may be considered as a possible contributing factor in our case.

Contrary to the cutaneous form, deep lesions tend to be well-circumscribed and pseudo-encapsulated with occasional areas of hemorrhage. Deep fibrous histiocytomas usually show a prominent storiform pattern, sometimes combined with hemangiopericytomalike areas. Contrary to conventional cutaneous lesions, most lesions present a certain monomorphism and usually lack secondary elements such as foamy cells and giant cells but usually show scattered lymphocytes. The tumor cells are cytologically bland and generally spindle-shaped with elongated or plump vesicular nuclei and eosinophilic, ill-defined cytoplasm. These lesions usually lack pleomorphism or hyperchromasia, and mitoses, although occasionally present, are usually less than 5 per 10 high power fields [3]. In BFH, immunohistochemistry is positive for CD68, 1-antitrypsin, 1-antichymotrypsin, and vimentin, whereas it is negative for cytokeratin, epithelial membrane antigen, smooth muscle actin, S-100 protein, and CD34 [25]. Solitary fibrous tumor differs from BFH as it is highly positive for CD34. Differentiation between BFH and neurofibroma (NF) can be based on NF positivity for S-100, and the presence of more frequent mitoses and different fascicle configuration in neurofibromas. The negativity for SMA and S-100 helps differentiation from leiomyosarcoma and neurogenic tumors [5].

Little is known on the possible genetic background leading to the formation of BFH most probably due to the rarity of the tumor and the minor importance it is granted when compared to malignant variants. There has been a single report of a t(16;17)(p13.3;q21.3) translocation in a deep BPH of the thigh [26]. Interestingly a large part of the cases of noncutaneous BPH reported in literature originate from the area of Far East; it is not clear whether this association is due to a major attention to the topic by the local medical communities or a truly higher incidence of the pathology in this region and whether a presumed higher occurrence rate is to be attributed to genetics, ambient factors or both.

The malignant variant of fibrohistiocytic tumors is considered as a highly aggressive sarcoma and is usually distinguishable from benign variants not only by its aggressive clinical course but also by the high mitotic rate cellular pleomorphism and atypical cells and by the tendency versus surrounding tissue invasion [27, 28]. In some cases however differential diagnosis might be challenging [29]. Not without extensive questioning on the exact histopathological and clinical profiles of the cases by the reporting authors, there have been reports of malignant fibrous histiocytoma arising in the same site or close proximity of a previously excised lesion defined as BFH [28, 29].

Atypical fibrous histiocytoma (atypical fibroxanthoma) is a distinct clinical and pathological entity with intermediate histological characteristics that make it resemble malignant lesions although it still remains clinically benign [27].

Given the good visibility of the lesion, in our opinion, localizations in the most external part of the nasal cavities such as the case presented, do not require the same radiological work up (CT and eventual RM) as those located deeper in the nose, unless bone involvement is presumed or other elements of suspicion are present in a thorough endoscopic examination.

Contrary to the malignant variants that require aggressive treatment strategies (extensive surgery and/or chemoradiation), a review of current medical literature reveals that local excision and mid-term follow up (12-24 months) appear to be sufficient for BFH [1, 5, 7, 8, 16].

A review of medical literature gives evidence that BFH should be taken into consideration when evaluating lesions of the head and neck region including the nose and that local excision and histopathological analysis with the use of immunohistochemistry is generally necessary to confirm the diagnosis and definitely rule out malignancy. We also believe that cases such as the one presented hereby prove that vestibular lesions should not be ignored or “a priori” considered of sole epithelial origin.

We declare that patient's specific written consent was obtained prior to diagnostic and therapeutic procedures and the preparation of the current manuscript and that ethical and legal principles as expressed by local committees and relative national legislation were respected.

The authors have no conflicts of interest to declare.

We state that all authors have contributed in the creation of the article by collecting the necessary material, writing and reviewing parts or the whole article and that all have approved its final version. Specifically: IM reviewed the patient's medical records in order to collect all available information, drafted and prepared the manuscript; IM and BP were responsible for the review of literature; EE, BP, AM and FM were involved in revising the article for clinical and pathological details regarding the case exposition and the contents of the discussion on it; EE and BP were responsible for diagnosing and performing surgery on the patient.