D
eep angiomyxoma (DAM) is a very rare, slow-growing benign tumor with a high risk of local recurrence after surgical resection. This tumor is more common in women, and its most common loca- tion is the pelvic genitourinary organs [1-5]. An accu- rate diagnosis of DAM is essential due to the local recurrence risk, but the diagnosis can be difficult, involving challenges in clinical practice. Herein, we describe an extremely rare case of DAM in the thigh that was misdiagnosed as a desmoid-type fibromatosis, and we present a review of available literature. The patient and her family were informed of our intention to submit the data from this case for publication, and they gave their written consent.Case Presentation
A 40-year-old Japanese woman with no history of any previous disease presented at our outpatient clinic due to a mass and slight pain on her left thigh that had
persisted for 3 months. Physical examinations revealed a small, hard lump on the inside of the left thigh.
Magnetic resonance imaging showed a large tumor (max. dia. 187 mm) spreading subcutaneously inside the thigh. The tumor showed iso-signal intensity on T1-weighted images (Fig.1A) and low-to-high intensity on T2-weighted images (Fig.1B,C). To exclude soft tissue sarcoma, we performed a needle biopsy to sam- ple the tumor, and in the histopathological examina- tion, a mild proliferation of spindle-shaped cells with poor atypia was observed against the background of a fibrous substrate; vascular intervention and some mature adipose tissue were also observed (Fig.2A). In immunohistochemical staining, vimentin was positive, smooth muscle actin (SMA) was partially positive, CD34 was negative, and the positive rate of Ki-67 was 1-2%. β-catenin was confirmed to be positive in both the nucleus and cytoplasm in some spindle-shaped cells (Fig.2B). The diagnosis of desmoid-type fibromatosis was thus made.
Internal medicines of tranilast (300 mg/day) and Hiroyuki Tsuchiea＊, Naohisa Miyakoshia, Hiroyuki Nagasawaa, Hiroshi Nanjob, and Yoichi Shimadaa
Departments of aOrthopedic Surgery, bPathology, Akita University Graduate School of Medicine, Akita 010-8543, Japan
We present an extremely rare case of deep angiomyxoma (DAM) in the thigh that was misdiagnosed as des- moid-type fibromatosis. A 40-year-old Japanese woman presented with a mass on the left thigh. The histologi- cal diagnosis by needle biopsy was desmoid-type fibromatosis; the tumor grew slowly and was resected 4 years later. The histological diagnosis from the resected tumor was DAM. As of 16 months post-surgery, the patient has not noticed any local recurrence. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence in areas relatively close to the pelvis.
Key words: deep angiomyxoma, thigh, desmoid-type fibromatosis
Received January 16, 2021 ; accepted April 15, 2021.
＊Corresponding author. Phone : +81-18-884-6148; Fax : +81-18-836-2617
E-mail : [email protected] (H. Tsuchie) Conflict of Interest Disclosures: No potential conflict of interest relevant to this article was reported.
meloxicam (10 mg/day) were prescribed to the patient.
However, the tumor showed a tendency to gradually grow. Another needle biopsy was performed 9 months after the patient’s first visit, but the pathological find- ings were similar to those previously collected. The patient did not want to have the tumor removed surgi- cally, and she continued taking tranilast and meloxi- cam. The tumor continued to grow slowly (Fig.3A,B),
and at 4 years after her first visit the patient requested surgical resection.
We resected the tumor extensively and reconstructed the surface layer with skin grafting (Fig.4). The histo- pathological examination revealed that the tumor area was covered with a fibrous capsule at the margin, and no infiltration into fat or muscle tissue was observed.
The inside of the tumor was mostly a wavy and bun-
Ａ
C
B
Fig. 1 MRI with axial views of T1-weighted (A) and T2-weighted (B) images and a coronal view of a T2-weighted image (C). The tumor reveals iso-signal intensity on T1-weighted images and low-to-high intensity on T2-weighted images.
Ａ Ｂ
Fig. 2 Histopathological findings from a needle biopsy from the thigh tumor are visualized with hematoxylin and eosin (H&E) staining (A) and immunohistochemical staining of β-catenin (B). The histopathological examination revealed a mild proliferation of spindle-shaped cells with poor atypia against the background of a fibrous substrate (A). β-catenin was confirmed to be positive in both the nucleus and cytoplasm in some spindle-shaped cells (B).
dle-like growth of sparse spindle-shaped cells, with the invasion of capillaries and collagen fibers; atypical and mitotic figures were not observed inside the tumor (Fig.5A). In immunohistochemical staining, vimentin, SMA, desmin, estrogen receptor, and progesterone receptor were positive, CD34 was partially positive, and the positive rate of Ki-67 was <1%. In addition, high mobility group AT-hook 2 (HMGA2) was slightly positive (Fig.5B). However, β-catenin was negative
(Fig.5C). Based on these histological features, a con- ference of multiple pathologists arrived at the consensus diagnosis of DAM.
The postoperative course was uneventful, and the patient walked without pain. She has not noticed any local recurrence as of the most recent follow-up, 16 months post-operatively.
A B
Fig. 3 MRI axial view (A) and coronal view (B) of T2-weighted (B) images. The tumor continues to grow.
A B
D C
Fig. 4 Intraoperative photographs. The tumor presented as a small, hard lump on the inside of the patient's left thigh (A), and the tumor was extensively resected (B,C). We reconstructed the surface layer with skin grafting (D).
Discussion
The first report of DAM was provided in 1983 by Steeper and Rosai [1], and this tumor has been reported to be a rare benign mesenchymal tumor.
DAM generally occurs in the reproductive organs of women, and it is most common in the vulva and pelvic cavity [2-5]. However, in a few cases, DAM has occurred in the testes and spermatic cords of men [6,7].
Most DAM tumors occur in the pelvis, and there are few reports of tumors occurring in a lower extremity, as in our patient’s case. Heffernan et al. reported a case of DAM that developed subcutaneously in the proximal thigh [8], and Zou et al. described 27 cases of DAM, two of which were in the lower limbs, including the knee [5]. There are reports of various sites of the occur- rence of superficial angiomyxomas, such as in the lower extremities [9,10]. Although the term ‘superficial angi- omyxoma’ sounds similar to ‘deep angiomyxoma (DAM),’ it is an entirely different disease from DAM.
There are only three prior reports of DAM at a lower extremity, as a very rare site of occurrence; the diag- nosis in our patient’s case was a challenge. We may need to consider the possibility of DAM not only in the pelvis but also around the pelvis.
The diagnosis of DAM based on imaging alone is difficult, and an evaluation using a sufficient amount of tissue is required [11]. Clinically, DAM may be mis- taken for a lipoma, vulvar abscess, or Gartner’s duct cyst; however, even with a histological diagnosis, it may be difficult to distinguish DAM from other myxoid neoplasms such as myxoid liposarcoma [12,13]. It is thus often difficult to make the correct diagnosis even when a histological examination is performed, and the misdiagnosis rate for DAM is reported to be 25.9-82%
[2,5]. In our patient’s case, the initial diagnosis was desmoid-type fibromatosis; however, there are no pre- vious reports stating that a DAM was mistaken for des- moid-type fibromatosis. We found that the partial positivity of β-catenin confirmed in the tissue used in our patient’s first needle biopsy had significant influence in the diagnosis. DAM is stained with immunostaining markers such as vimentin, desmin, CD34, estrogen receptor, and progesterone receptor, but there have been no reports on β-catenin in DAM. In our patient, no positive image was confirmed in the tissue after exci- sion; thus, it is most likely that DAM is basically unstained, and this was observed in our patient’s case.
The HMGA2 gene encodes a protein that alters the chromatin structure and regulates the transcription of
A B
C
Fig. 5 Histopathological findings of the excised tumor: H&E staining (A). Immunohistochemical staining of high mobility group AT-hook 2 (HMGA2) (B) and β-catenin (C). In the histopathology, the inside of the tumor was mostly a wavy and bundle-like growth of sparse spindle-shaped cells and the invasion of capillaries and collagen fibers, and atypical and mitotic figures were not noticeable inside the tumor (A). HMGA2 staining was sparsely positive (B). However, β-catenin was negative (C).
is a useful indicator for the diagnosis of DAM.
Desmoid-type fibromatosis is generally referred to as one of the most difficult tumors to diagnose, and there is sometimes a change in a diagnosis from before to after an excision. Kasper reported a misdiagnosis rate of 30-40% in desmoid-type fibromatosis [16]. There are many cases of mutations in CTNNB1 in desmoid-type fibromatosis; CTNNB1 is a β-catenin gene, and the analysis of these gene mutations can improve the accu- racy of diagnosis [17]. It may be advisable to conduct such an analysis in cases in which desmoid-type fibro- matosis is suspected, in order to prevent a misdiagno- sis.In conclusion, we have presented an extremely rare case of DAM on the thigh that was misdiagnosed as desmoid-type fibromatosis. Although DAM in a lower extremity is extremely rare, clinicians must be aware of its possible occurrence at body sites that are relatively close to the pelvis.
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