Journal of Medical Sciences and Health

Introduction

Hemosiderotic Fibrohistiocytic Lipomatous Tumor (HFLT), Pleomorphic Hyalinizing Angiectatic Tumor (PHAT), and Myxoinflammatory Fibroblastic Sarcoma (MIFS) are rare mesenchymal neoplasms with a tendency for the distal lower extremities. Although each of these entities have been described independently in literature, various histological and genetic observations over the past two decades have led to speculation that these tumors may be interrelated. This hypothesis is based on both histomorphological and genetic features, but the exact relationship between these three entities remains a topic of controversy and debate for the scholars. In this article, we have analyzed the key histomorphologic and immunohistochemical (IHC) features of a case of HFLT which showed an unusual clinical presentation and a discussion about the closest differentials which easily confuses the pathologist and lead to chances of misdiagnosis. Since the available literature over these entities are limited, we hereby will evaluate the relationship between these tumors.

The spectrum of lipomatous lesions ranges from

Case presentation

A 63-year-old male presented to surgery department of our institution with a painless swelling over upper one third of right thigh. The patient had noticed the lesion one and a half year before, which has gradually progressed to the present size (24×12 cm). There was no significant medical history or history of trauma. Family history was noncontributory. On physical examination, swelling was 24x12 cm with ill-defined margins, which was non tender, with no local rise of temperature. On further examination, patient had difficulty in flexion and external rotation of thigh and a resistance involving half the anterior medial side of the thigh was present. MR imaging revealed lipomatous lesion of the right thigh measuring 28× 13 × 10 cm with irregular boundaries. The lesion showed multiple far-reaching intramuscular and subfascial extensions. The assessment of internal structures showed a homogeneous, lobulated lesion suspicious of liposarcoma.

Complete tumor resection was performed with free margins. After resection the specimen was subjected to histopathological evaluation.

The specimen was fixed in 10% neutral formalin, then conventional paraffin sectioning and hematoxylin and eosin (H&E) staining were performed. The morphology of tumor tissue was observed under a light microscope.

On gross examination, lipomatous lesion measured 28×13×10cm. It was darker yellow than the normal surrounding fat. External surface was well circumscribed, congested and showed blood vessels. Cut surface showed collated appearance. Cystic areas were filled with necrotic debris and hemorrhagic areas were made out (Figure 1).

Microscopically, ten representative samples throughout the whole tumor were reviewed. Histopathological examination revealed a neoplastic lesion composed of spindle cells infiltrating into adipocytic component in a honey comb pattern . These spindle cells had elongated, vesicular nuclei, inconspicuous nucleoli and scanty cytoplasm. The adipocytic component was mature without atypia and no lipoblasts were seen. There were numerous small to large ectatic blood vessels with a number of them showing organising thrombi, aggregates of histiocytes containing hemosiderin pigment (Figure 2). No evidence of increased mitotic activity was noted. On IHC staining of CD34, a notable diffuse staining primarily of the spindle cells, fibrocytes and vascular endothelium was seen (Figure 3). On staining with CD68 we found out positive staining for macrophage lineage such as tissue histiocytes. (Figure 4)

By combining histology and IHC features of resected specimen with clinical information, the diagnosis of HFLT was established. There were no operative or post-operative complications noted. Eighteen months after the excision, the patient continued to show no signs of recurrence.

Methods

We reviewed 67 cases of HFLT from the literature, published in English and Portuguese language which were available at Pubmed data base (Table 1).

Case reports, articles that diagnosed HFLT with adequate evidence supported by gross examination, histology, biopsy and previous recurrrences were included. Demographic data such as age at diagnosis, gender, location and size were recorded. An attempt to look for clinico-pathologic features of HFLT along with IHC features was done. All the 67 cases were studied using descriptive statistics.

Results

The demographic characteristics of all HFLT included were studied and tabulated (Table 2). Our review of the literature suggests that HFLT predominately presents in middle-aged women (median age being 50 years and mean age being 51 years). Age group ranged from 7 months to 78 years, the ratio of male to female was 1: 2.6 with close to half (46%) the cases having a history of trauma or vascular disease.

HFLT occurs within the soft tissue of limb extremities, with foot/ankle accounts for 77%, but also involves the hands,1, 2, 3 forearm,4, 5 wrist6 and one case involving cheek and finger. 7

It has been reported that majority cases of HFLT are characterized by CD34 expression in spindle cells and vascular endothelium.

It was noted that HFLT needs to be pathologically distinguished from related adipocytic lesions such as PHAT and MIFS which share similar location and morphologic characteristics. Summary of key morphological and genetic features of adipocytic lesions are tabulated in Table 3.

Discussion

HFLT is a rare benign fibrolipomatous lesion first described as an entity in 2000 by Marshall - Taylor and Fanburg - Smith. It accounts for 0.2% of benign lipomatous lesion. 7

HFLT generally affects the ankle and the dorsum of the foot, although it may appear in other locations such as cheeks and hands. It typically affects adults, more commonly females, in the 5th and 6th decades of life. The distinct feature about our case is its huge size, site and occurrence in male. Thigh is not the usual site of presentation. Our case and only two other cases in literature (de Vreeze et al. 11 and Etchebehere et al.20) have reportedthigh as the location.

Histologically, it is characterized by a lipomatous lesion composed of three elements occurring in varying proportions. These elements include mature adipocytes, spindle cells and hemosiderin pigment, which is present predominantly in macrophages within the spindle cell areas, whose original deposit is unclear. The mature adipose tissue is infiltrated by strands of fibrous tissue featuring fibroblastic spindle cells and hemosiderin deposits.

Scattered areas with atypical pleomorphic cells may be present. Focal clusters of ectatic blood vessels as seen in PHAT are not uncommon. Chronic inflammatory cells are usually seen in the background. Mitosis or necrosis are usually not seen. CD34 positivity clearly differentiates the fibroblastic differentiation while CD68 positivity shows diffuse staining for the macrophages. ¹

Conclusion

Ambiguity existed about reactive or neoplastic origin of HFLT. It is now well-established on the basis of histomorphology and molecular genetic evidence that HFLT and PHAT represent different manifestations of a single entity, with HFLT representing the precursor or “early” lesion of classic PHAT. The hallmark of these lesions is complex admixture of mature adipose tissue, spindle tumor cells with striking deposition of hemosiderin pigment. Even though HFLT shows marked prediliction for the distal extremeties especially the foot/ ankle and female gender, they can occur at uncommon site such as thigh and in a male patient as seen in our case.

Abbreviations

HFLT: Hemosiderotic Fibrohistiocytic Lipomatous Tumor; PHAT: Pleomorphic Hyalinizing Angiectatic Tumor, MIFS: Myxoinflammatory Fibroblastic Sarcoma; TGFBR3: Transforming Growth Factor Beta Receptor 3; MGEA5: Meningioma Expressed Antigen 5; IHC: Immunohistochemical

Conflict of interest

Nil