Clinical data were collected from the medical records of eight patients diagnosed with lipidized FH from November 2019 to November 2021. The diagnosis was confirmed by Dr Zhao Ming (Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China). A total of three cases originated from the tissue bank of the Department of Pathology of the Peoples' Liberation Army 989 Hospital (Pingdingshan, China), four cases originated from the tissue bank of Fenlan Medical Laboratory (Hangzhou, China) and one case originated from the tissue bank of Department of Pathology of Yexian People's Hospital (Pingdingshan, China). The cohort included three male and five female patients (male: female ratio, 1.7:1) with a mean age of 48 years (range: 38-62 years). The present study was approved by the 989 Hospital Medical Ethics Committee, Fenlan Lab Medical Ethics Committee and Yexian First People's Hospital Committee. All participants signed an informed consent form and all patient data were anonymized. The inclusion criterion was a diagnosis in accordance with lipidized FH.

Hematoxylin and eosin-stained slides were available for all cases and this staining was conducted using a method described by Sommer et al (6). The surgical specimens were fixed in 10% neutral buffered formalin in the room temperature, dehydrated in graded alcohol solutions and embedded in paraffin. Specimens were cut into 4-µm-thick sections for hematoxylin and eosin staining and visualization was carried out using light microscopy.

Sections (4-µm) from paraffin blocks were also stained immunohistochemically using BOND-MAX Automated IHC/ISH Stainer (Leica Microsystems GmbH). Sections were mounted onto slides, air dried for 20 min and baked at 60˚C for 20 min. The heat-induced antigen retrieval method was performed using Tris-EDTA buffer (1X; cat. no. #K0071; Shanghai Jiehao Biotechnology Co., Ltd.) and endogenous peroxidase activity usually responsible for background staining, was quenched with 3% peroxidase-blocking reagent, (Henan Celnovte Biotechnology Co., Ltd.), which was applied at 37˚C for 10 min. The slides were incubated with the following commercially available antibodies: CD68 (cat. no. CCR-0702; KP1; 1:1,000), smooth muscle actin (cat. no. CAM-0190; IA4; 1:50), S-100 protein (cat. no. CSM-0101; polyclonal; 1:500), CD34 (cat. no. CCM-0550; QBend10; 1:50), desmin (cat. no. CDM-0021; D33; 1:50), MUC4 (cat. no. CMM-0270; 8G7; 1:50) and cytokeratin (cat. no. CCM-0960; AE1/AE3; 1:50) at 37˚C for 30 min. All antibodies were purchased from Henan Celnovte Biotechnology Co., Ltd. The sections were then examined using a light microscope. Tissue sections were then washed (2x6 min) and incubated with Microstacker™ + Linker in room temperature for 15 min for signal amplification. After TBS washing (2x6 min), Microstacker™ Flex HRP-polymer detection reagent (ready-to-use; cat. no. #SD5100; mouse/rabbit linker; Celnovte Biotechnology Co., Ltd) was applied for at 37˚C for 30 min. After incubation with the polymer reagent, tissue sections were thoroughly washed with TBS buffer (3x6 min) and incubated with Microstacker™ DAB + Chromogen at 37˚C for 6 min. Slides were buffer washed (2x6 min), counterstained with hematoxylin at 37˚C for 2 min and washed with TBS and dH₂O for 6 min respectively. Ultimately, dehydration through graded ethanol solutions as well as 90% xylene was performed and sections were mounted in synthetic resin and were observed under a light microscope.

The IHC results were scored by two independent observers according to the percentage of positively stained cells (0+, 1-25% staining; 1+, 26-50% staining; 2+, 51-75% staining; 3+, 76-100% staining).

The patient cohort included three males and five females with a mean age of 48 years (range, 38-62) at the time of diagnosis (Table I). Clinical symptoms were recorded in all eight cases. All patients reported the presence of a mass with no other complications. The preoperative duration ranged from 11 months to 6 years. All eight cases were followed up. None of these tumors had recurred locally at 6 to 24 months (median, 13.6 months) after the operation. No cases exhibited a history of hypertension, diabetes or hyperlipemia. A total of three tumors were located on the right buttock, one on the left buttock, one on the left lower leg, one on the right lower leg, one on the right shin and one on the left forearm.

Grossly, all cases demonstrated a well-demarcated lesion, and lesions were elevated. The average tumor diameter was 21 mm (range, 7-35 mm). The cut surface of the lesions was yellow with parts that were white (Fig. 1).

There were solitary nodules in the reticular dermis. The nodules were well circumscribed; however, no fibrous or capsule-like membrane was revealed (Figs. 2A, 3A and 4A). The nodules were comprised of two markedly different components: Proliferating eosinophilic fibroblasts and lipid-laden histiocytes. In the majority of areas, the fibroblasts exhibited no cytologic atypia, with elongated nuclei, fine chromatin and small basophilic nucleoli. However, nuclear pleomorphism was present in the deep or peripheral area. Notably, no pathological mitotic figures were observed. The fibroblasts were arranged in a storiform pattern or with intersecting fascicles forming a loose lattice pattern (Figs. 2B, 2C, 3B and 4B). The histiocytes were oval to polygonal in shape with large hypochromatic nuclei, prominent nucleoli and abundantly vacuolated cytoplasm (Figs. 2D, 3C and 4C). In the majority of areas, histiocytes were combined with proliferating eosinophilic fibroblasts. There were also a number of binucleated or multinucleated Touton-type giant cells (Fig. 3D). Notably, there was marked stromal hyalinization, which was observed in >90% of the tumor area (Figs. 2C, 3B and 4C). Hyalinized collagen fibers transmigrated with normal collagen fibers (Fig. 2E), and the hyalinized materials exhibited different colors in microscopy; notably, certain areas presented as bright red and others presented as dull red (Figs. 2A, 3A and 4A). The bright red areas were rich in lipid-laden histiocytes and the dull red areas possessed fewer lipid-laden histiocytes. There were prominent hyalinized vessels in some cases (Fig. 2E). The epidermis exhibited hyperplasia, irregular elongation of the rete ridge, and basal pigmentation (Figs. 2A and 3A).

Immunohistochemical staining was positive for CD68 (Figs. 2F and 4D), focally positive for CD34, particularly in the peripheral region of the lesion, and negative for S-100 protein, smooth muscle actin, desmin, MUC4 and cytokeratin. These histopathologic findings led to the diagnosis of lipidized FH.