Keywords
CD34 - immunohistochemistry - mesenchymal tumors - superficial sarcoma - fibroblastic
tumor - cytology
Introduction
Superficial CD34-positive fibroblastic soft-tissue tumor is a rare condition, with
52 cases reported in the literature to date.[1] It is characterized by marked pleomorphism, low mitotic activity, CD34 immunoreactivity,
and slow, progressive growth. It is believed to behave as a mesenchymal tumor of intermediate
malignancy; however, due to the little information and scarce follow-up reports in
the literature, the best treatment for this condition is yet to be determined. We
present a case of a patient with a long-standing inguinal mass which was completely
resected through surgery with adequate outcomes and no recurrences or complications
during an 18-month clinical follow-up.
Case description
A 31-year-old female patient felt a mass in the left inguinal region for 10 years;
it grew slowly and progressively, and started to cause pain in the proximal third
of the left thigh in the previous year. Clinically, she presented a left inguinal,
well-defined mass, close to the ischiopubic ridge, painful on palpation, with no skin
or gait changes. Magnetic resonance imaging (MRI) scans revealed a well-defined, 3-cm
x 4-cm lesion which was hypointense on T1-weighted and hyperintense on T2-weighted
sequences, located on the medial aspect of the left thigh ([Fig. 1]).
Fig. 1 Hip magnetic resonance imaging scan revealing a superficial lesion on the medial
aspect of the thigh, with well-defined edges, which were hypointense on T1-weighted
images and hyperintense on T2-weigthed images.
Biopsy of the lesion was indicated for its characterization due to its size and the
patient's pain complaints in recent months. The pathology report indicated the presence
of a left inguinal mass with myxomatous features. The mass was positive for CD34,
but negative for CD31, S100, SOX10, CK, desmin, signal transducer and activator of
transcription 6 (STAT6) and estrogen receptors, among other markers. The characteristics
of the lesion hindered its classification, and the mass was deemed a potential sarcoma.
The patient's case was presented to a medical board consisting of pathology, plastic
surgery, and orthopedic oncology specialists, who decided for an en bloc resection
of the lesion with widened margins and defect reconstruction with an advancement flap.
The procedure was performed with no complications ([Fig. 2]).
Fig. 2 (A) Mass in the inguinal region; (B) lesion resection and reconstruction with a local flap.
A gross pathology study revealed a superficial lesion, with well-defined edges, partially
covered by skin ([Fig. 3]). A histopathology analysis revealed a lesion with sheets of pleomorphic cells mixed
with clear xanthomatous cells, ([Fig. 4]) and no high mitotic count or necrosis; the lesion borders were negative for tumor.
With these findings, several differential diagnoses were initially raised, including
sarcomatoid carcinoma, melanoma, and atypical fibroxanthoma (FXA); however, there
was no contact with the epidermis, however, there was no contact with the epidermis.
Cytokeratins AE1AE3-CAM5.2, and proteins P.63, P.40, S100, SOX11, and MELAN A were
negative, ruling out carcinoma and melanoma. Since the lesion occured on an area of
skin with no sun exposure, FXA was ruled out; in addition, the mass was very large
and deeply compromised. Diffuse CD34 reactivity ([Fig. 5]) broadened the diagnostic spectrum to include myxofibrosarcoma (which usually presents
arcuate vessels and frequent mitoses in cases of high-grade lesions, as well as partial
and not diffuse CD34 reactivity); vascular tumors, such as pleomorphic angiosarcoma
(but there was no mitosis, the growth pattern was not infiltrative, and it was negative
for Transmembrane E3 ubiquitin-protein ligase (FLY-1), cluster differentation 31 (CD31)
and transcriptional regulator (ERG) were negative); and three related entities. The
first was pleomorphic angiectatic tumor, but no ectatic vessels with peripheral fibrin
deposits were found. The second one was myxoinflammatory fibroblastic sarcoma, but
this is usually distally located and presents Reed-Sternberg-like cells and pseudolipoblasts;
although it may exhibit CD34 reactivity, it is usually focal. The last differential
diagnosis was a superficial CD34-positive fibroblastic tumor; no reactivity was found
for desmin, AML or EMA, and there was no loss of INI-1. Fluorescent in situ hybridization
for Transforming growth factor beta receptor type 3 (TGFBR3) or meningioma expressed
antigen 5 (mgea5) was not available at our institution.
Fig. 3 Gross appearance of the inguinal tumor lesion.
Fig. 4 Intermixed sheets of xanthomatous cells with no mitosis (hematoxylin-eosin, 40x).
Fig. 5 Diffuse CD34 reactivity (10x).
We concluded that this was a pleomorphic spindle cell tumor consistent with a superficial
CD34-positive fibroblastic tumor.
During the 18-month clinical follow-up, the patient presented an adequate evolution,
with proper wound healing and flap integration, in addition to no pain; there were
no secondary complications or new lesions, and functionality was deemed adequate.
Discussion
Superficial CD34-positive fibroblastic tumor is rare and characterized by abundant
pleomorphism, low mitotic activity, and CD34 immunoreactivity; it grows slowy and
progressively. It usually occurs in the lower limbs, including the thigh, knee, buttocks,
leg, and foot, and it is less frequent in other sites such as the arm, inguinal region,
vulva, hip, shoulder, and neck. They are usually circumscribed lesions with subcutaneous
presentation, with little or no deep-muscle involvement, as in our case.[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
The first case was described by Carter et al.[3] in 2014, and, to date, 52 cases have been identified.[1]
[2]
[3] The literature presents only case reports, which makes it difficult to establish
a treatment guide or clear evidence regarding surgical management and adjuvant modalities,
such as chemotherapy or radiotherapy, for this type of tumor. However, the available
information reveals good outcomes after surgical resection, with no postoperative
local recurrences. The symptoms are highly variable, with disease onset up to 20 years
before the surgical intervention.
As for pathophysiology, a behavior similar to that of a mesenchymal tumor of intermediate
malignancy has been reported. The latest World Health Organization (WHO) classification
of musculoskeletal tumors,[10] published in 2019, places this neoplasm within the group of fibroblastic/myofibroblastic
tumors with intermediate, rarely metastatic behavior; rearrangements in domain zinc
finger protein 10 (PFMR10) have been reported in some, and, so far, occasional cases
with lymph node metastasis.
On histopathology, this tumor is characterized by pleomorphic, polygonal tumor cells
oriented in sheets or fascicles, with abundant eosinophilic cytoplasm, hyperchromatic
nuclei, and multiple nucleoli.[4]
[6] Regarding immunohistochemistry, Lao et al.[6] report a strong, diffuse expression of CD34 at 100%, AE1/AE3 at 57%, and CAM5.2
at 50% with a low Ki67 index (1%) and negative findings for EMA, SMA, desmin, h-caldesmon,
calponin, myogenin, myoblast determination protein 1 (MyoD1), S100 protein, transcription
factor SOX-10, glial fibrillary acidic protein (GFAP), anti-melanoma monoclonal antibody
HMB45, melan-A protein, CD31, ERG, STAT6 and anaplastic lymphoma kinase (ALK), findings
that are consistent with those reported by Riddle et al.[4] and Li et al.[5] In 2014, in a series of 18 patients, Carter et al.[3] suggested that this entity must be considered a lesion of borderline malignancy.
Differential diagnoses include undifferentiated pleomorphic sarcoma, dermatofibrosarcoma
protuberans, and myxofibrosarcoma.[3]
[4] Correct differentiation of this type of tumor is critical for an adequate, timely
treatment.
Conclusions
Superficial CD34-positive fibroblastic tumor is infrequent, with only 52 cases reported
in the literature; it behaves as an intermediate-grade mesenchymal tumor, and its
prognosis is excellent according to WHO[10] recommendations. Broader case series with long-term follow-ups are required to establish
treatment protocols for this condition in terms of surgical management and potential
adjuvant therapy.
