Superficial CD34-Positive Fibroblastic Tumor: Report of an Extremely Rare Entity.

Superficial CD34-positive fibroblastic tumor (SCPFT), a newly described neoplasm is a rare mesenchymal neoplasm of intermediate malignancy. A 63-year-old man presented with a painless, slow-growing, skin-colored nodule of 8 × 4 mm in diameter on the right side of the neck. It was completely resected. Histologically, a tumor located in the subcutis with the minimally infiltrative pattern was detected. The tumor was composed of variably enlarged bizarre and pleomorphic spindle to polygonal cells. Tumor cells were stained strongly diffuse positive with CD34 and weak positive with keratin, negative with STAT6, FLI-1, ERG, S100, desmin, and smooth muscle actin. The fluorescence in-situ hybridization (FISH) analysis was negative for COL1A1 gene rearrangement. As per the findings, the case was diagnosed as a SCPFT. It is a borderline mesenchymal neoplasm occurring within the superficial soft tissues with distinctive morphological and immunohistochemical features. Copyright:

Introduction

Superficial CD34-positive fibroblastic tumor (SCPFT) is a rare mesenchymal neoplasm of borderline (intermediate) malignancy. SCPFT was first described by Carter et al. in 2014 in a series of 18 cases.[1] To date, 35 cases of SCPFT have been described histopathologically and immunohistochemically.[23]

Case Report

A 63-year-old man was admitted to the hospital with painless, slow-growing, skin-colored nodule on the right side of the neck for 3 months [Figure 1]. Superficial ultrasonographic examination of the lesion revealed a nonvascular, hypoechoic, nodular lesion with a diameter of 8 × 4 mm. A diagnostic excisional biopsy was performed. Macroscopically, a tumor 8 × 4 mm in diameter with firm, tan-yellow, relatively infiltrated in the deep dermis and subcutaneous tissue was seen. Microscopically, a circumscribed tumor with focal infiltrative areas was seen in the deep dermis and subcutaneous tissue [Figure 2]. It was composed of moderately cellular fascicles and sheets of spindle to epithelioid cells in the deep dermis and subcutaneous tissue [Figure 3]. In some areas, striking nuclear pleomorphic with bizarre lobated and hyperchromatic nuclei containing multiple large prominent nucleoli were seen [Figure 4]. Mitosis was seen as 1/50 HPF. Atypical mitotic figures and necrosis were absent. There was mild amount of chronic inflammatory cells within the lesion.

Figure 1

Skin-colored nodule of 8 × 4 mm in diameter on the right neck

Figure 2

Tumor with moderately cellular fascicles and sheets of the spindle to epithelioid cells in the deep dermis and subcutaneous tissue (H and E, ×40)

Figure 3

Cellular fascicles and sheets of the spindle to epithelioid cells with striking nuclear pleomorphism (H and E, ×100)

Figure 4

Striking nuclear pleomorphism with bizarre lobated and hyperchromatic nuclei (H and E, ×400)

Immunohistochemically, strong and diffuse positivity with CD34 was detected [Figure 5]. In addition, focal weak positivity for keratin, negativity for STAT6, FLI-1, ERG, S100, desmin, and smooth muscle actin were seen. Loss of INI-1 was not seen.

Figure 5

Diffuse positivity for CD34 (IHC, ×400)

Fluorescence in situ hybridization (FISH) was performed using “The ZytoLight ® SPEC COL1A1 Dual Color Break Apart Probe, Z-2121-200, ZytoVision, Bremerhaven, Germany.” The orange fluorochrome direct labeled probe hybridizes distal and the green fluorochrome direct labeled probe hybridizes proximal to the COL1A1 gene (17q21.33). Deparaffinization, pre-hybridization, and hybridization were done according to the datasheet. One hundred tumor cells were analyzed on the fluorescent microscope (Leica DM 2500). The cells were captured on a computer system with a digital camera (Argenit-AKAS Imaging, Turkey). Signals from tumor cell nuclei were counted and the presence of red-green break-apart signals was recorded. FISH analysis was negative for COL1A1 gene rearrangement [Figure 6].

Figure 6

FISH analysis was negative for COL1A1 gene rearrangement

Discussion

SCPFT was recently described by Carter et al. in 2014 in a series of 18 cases.[1] To date, few cases counting only up to 35, of SCPFT have been reported.[23] This rarity is probably largely due to under-recognition.

In the literature, there are two big series, one with 18 cases from Carter et al. and the other with 11 cases from Loa et al.[13] SCPFT commonly affects adults with age ranging between 18 and 76 years.[13] The tumors most commonly occurred in the lower limb, thigh, buttock, shoulder, and upper arm. The most common presentation was a slow-growing, cutaneous painless mass or nodule, whereas two patients complained of mild tenderness.[3]

Microscopically, tumors are confined to the deep dermis and superficial fibroadipose tissue. It generally appears relatively circumscribed, but local infiltration into the adjacent adipose tissue can be seen. Tumor cells are composed of plump spindle to epithelioid cells with a granular, fibrillary, or glassy eosinophilic cytoplasm. They are arranged in short fascicles and sheets. The hallmark tumor cells are enlarged hyperchromatic bizarre-appearing nuclei, some of which possessed intranuclear cytoplasmic pseudoinclusion. Despite the bizarre appearing nuclei, extremely low mitotic activity is a rule (<1/50 HPF). In addition, mixed infiltration of chronic inflammatory cells, focal aggregation of xanthoma cells, hemosiderin deposits, and few elongated and dilated thin-walled vessels can be seen. However, thick-walled ectatic vessels are absent.[123456]

Immunohistochemically, all tumors are strongly positive for CD34. In addition, focal staining of AE1/AE3 and CAM5.2 can be seen. EMA, SMA, desmin, h-caldesmon, calponin, myogenin, MyoD1, S100 protein, SOX10, GFAP, HMB45, Melan-A, CD31, ERG, STAT6, and ALK are negative. Ki-67 index values are very low (1–5%).[123456]

Lao et al. studied FISH in five cases for PDGFB rearrangement and in four cases for ALK rearrangement. They did not show any rearrangement of PDGFB gene or ALK gene by FISH.[3]

Ultrastructurally, tumor cells exhibit irregular or convoluted nuclei with abundant euchromatin prominent nucleoli.[2] Some cells have various intermediate filaments, such as paranuclear and whorled, whereas others have a few filaments.[5] It was shown that t(2;5)(q31;q31) may be a disease specific chromosomal aberration in SCPFT in only one case.[2]

In differential diagnosis, atypical fibrous histiocytoma, atypical fibroxanthoma, pleomorphic dermal sarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, epithelioid sarcoma, hemangioendothelioma, dermatofibrosarcoma protuberans (DFSP), inflammatory myofibroblastic tumor, and malignant solitary fibrous tumor must be considered.[3789] Especially, subcutaneous variant of DFSP can be confused with SCPFT. It is a subcutaneous mass that shows no connection with the dermis and is immunostained for CD34 like SCPFT. Whereas the COL1A1-PDGFB fusion gene is expressed in DFSP, it is not seen in SCPFT as in our case.[7] This finding can help to differentiate SCFPT from subcutaneous DFSP.

The treatment of SCPFT is surgical total excision. To date, in English literature, the regional lymph node metastases after incomplete excision of SCFPT have been reported in only one patient, whereas in the remaining cases, recurrences or metastasis were not reported. Because SCFPT is a new tumor, clinical follow-up is very short in reported cases and long-term follow-up is appropriate.[13]

In summary, we report a new case of superficial CD34-positive fibroblastic tumor. It is characterized by a superficial location, striking cellular atypia, extremely low mitotic rate, and strong diffuse CD34 positivity, and negative for COL1A1 gene rearrangement. Based on limited available data, these tumors have intermediate (borderline) malignancy with rare metastatic potential. We think that recognition of the tumor is important to avoid confusion with other cutaneous pleomorphic soft tissue tumors, especially high-grade undifferentiated pleomorphic sarcoma to avoid unnecessary overtreatment.

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Conflicts of interest

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