Abstract
Background/Aim: The management of soft-tissue tumors of 2-5 cm is not specified. We investigated the management of these cases. Patients and Methods: Among 105 cases with soft-tissue tumors from 2014 to 2021, 38 with tumors of 2-5 cm were retrospectively reviewed. The clinical characteristics, diagnosis, and management were investigated. Results: The study population included 14 males and 24 females (mean age=57 years). Common histological diagnoses included lipoma, epidermal cyst, and hemangioma as benign tumors, and leiomyosarcoma (n=2) and metastatic soft-tissue carcinoma (n=1) as malignant tumors. Magnetic resonance imaging, needle and excisional biopsy were performed in 35, 19 and 19 cases, respectively. The mean follow-up period was 7 months. No recurrence was observed. Conclusion: Malignancy exists, even in soft-tissue tumors of 2-5 cm (3/38; 8%). To avoid unplanned excision, needle biopsy should be considered for cases with magnetic resonance imaging abnormalities.
Soft-tissue sarcoma is a rare cancer that arises at any site and at any depth in various sizes. In addition, various histological types exist according to the World Health Organization classification (1) and are sometimes hard to diagnose if the pathologist is not familiar with histology of musculoskeletal oncology.
Cutaneous or subcutaneous soft-tissue tumors are often treated by plastic surgeons or dermatologists in general hospitals or family clinics, and small tumors and tumors at superficial sites are usually excised following simple ultrasonography (2-5). In comparison to magnetic resonance imaging (MRI) or the histological examination of biopsy specimens, it is difficult to predict malignancy based on ultrasound findings, even when they are combined with clinical features (6-10).
Unplanned excision is defined as surgical excision without a close examination for soft-tissue tumors, which may cause local recurrence or metastasis of a soft-tissue tumor if the tumor has a malignant histology (11-14). Orthopedic surgeons and general surgeons as general practitioners in family clinics or working doctors in general hospitals sometimes conduct tumor excision without a close examination when they are not familiar with the management of soft-tissue tumors (2-5). This may be due to a lack of education when they were medical students or due to the poor familiarity with the difficulty of additional surgery after unplanned excision (5, 11-14).
According to the 2020 Japanese Orthopaedic Association Clinical Practice Guidelines on the Management of Soft-Tissue Tumors, soft-tissue tumors of ≤2 cm in size may be excised for excisional biopsy on the condition that they exhibit benign features on MRI imaging, are superficial, and are located away from important organs or structures (e.g., nerves or vessels). In contrast, in the management of soft-tissue tumors of ≥5 cm in size, needle biopsy should be performed to make a histological diagnosis before any treatment (15-17). However, the management of soft-tissue tumors of 2-5 cm in size was not specified in these guidelines, and the treatment strategy was left to doctors who encountered these tumors.
Small tumor size (≤5 cm) was reported to be a risk factor for unplanned excision, and all lumps larger than a golf ball (1.68-inch, 4.267 cm) should be suspected to be soft-tissue sarcoma (18-22). However, little is known about the actual strategy used to treat soft-tissue tumors of 2-5 cm in size in previous studies. We therefore investigated the characteristics and management of soft-tissue tumors of 2-5 cm in size in comparison to those of other sizes, in patients managed at our Institution.
Patients and Methods
One hundred and five patients were histologically diagnosed with soft-tissue tumors at our Institution from March 2014 to November 2021. All of these patients were enrolled in the present study. Using medical records, the following factors were investigated: Age, sex, tumor size, tumor site, depth, initial symptoms, MRI, biopsy (needle or excision), histology, histological grade (malignancy or benign), treatment (operation, observation, or referral to specialized hospital), follow-up period, and oncological outcome at the final follow-up examination. The tumor size was defined as the length in the greatest dimension measured on MRI, or on the excisional biopsy specimen when an MRI examination was not conducted. The patients were divided into three groups according to tumor size: ≤2 cm, 2-5 cm, and ≥5 cm. The tumor site was classified as the trunk or appendicular skeleton. The tumor depth was classified as superficial or deep. The initial symptoms included mass, increasing mass, painful mass, and other. The histology and its grade were classified according to the World Health Organization classification (1).
This retrospective study of patient specimens was approved by the Ethical Committee of Kanazawa Red Cross Hospital (Institutional Review Board Number 587) and was performed in compliance with the guidelines of the 1975 Declaration of Helsinki. Written informed consent was obtained from all study participants or their parents (in the case of children).
Statistical analysis. A one-way analysis of variance was used to compare age, tumor size, follow-up period among the three groups, while a chi-squared test was used to compare sex, tumor site, depth, initial symptom, MRI, needle biopsy, excisional biopsy, and histological grade. In both tests, values p<0.05 were considered to indicate statistical significance. All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for the R software program (The R Foundation for Statistical Computing, Vienna, Austria) (23).
Results
Patient characteristics. The number of patients in groups with tumor of ≤2 cm, 2-5 cm, and ≥5 cm was 44, 38, and 23, respectively. The patient characteristics are shown in Table I. The 2-5 cm group included 14 male patients and 24 female patients, and the sex predominance was similar to the other size groups (p=0.89). The mean age of patients of the 2-5 cm group was 57 years, and younger than that of the ≥5 cm group (73 years; p<0.01). Tumors in the 2-5 cm group were located more frequently on the appendicular skeleton (32/38; 84%) and were superficial (31/38; 82%), while tumors in the ≥5 cm group were located more frequently on the trunk (12/23; 52%) and were deep (11/23; 48%) (both p<0.01). The distribution of initial symptom (mass, increasing mass, pain/painful mass) and other [numbness (n=2); paralysis (n=1); no symptom (n=1)] was similar among all groups (p=0.31).
Patient characteristics according to the size of soft-tissue tumors.
MRI examination and biopsy methods. MRI examination was performed for 91-100% of the patients in each group (p=0.34). Needle biopsy was performed more frequently in the ≥5 cm group, and excisional biopsy more often in the ≤2 cm group (both p<0.01). In the 2-5 cm group, the biopsy methods were decided depending on the case [needle biopsy in 19/38 (50%); excisional biopsy in 19/38 (50%)].
Histology. Malignant histology was found in 0/44 (0%), 3/38 (8%), and 5/23 (22%) patients in the ≤2 cm, 2-5 cm, and ≥5 cm groups, respectively (p<0.01). The distribution of the histological diagnoses is shown in Table II. Leiomyosarcoma (n=2) and metastatic soft-tissue tumor of renal pelvis carcinoma (n=1) were recorded in the 2-5 cm group, while diffuse large B-cell lymphoma (n=2), dedifferentiated liposarcoma (n=1), spindle cell sarcoma (n=1), and epithelioid hemangioendothelioma (n=1) were observed in the ≥5 cm group. The most common benign histological diagnosis was epidermal cyst in all groups. Hemangioma, vascular leiomyoma, and schwannoma were commonly observed as benign soft-tissue tumors in the ≤2 cm and 2-5 cm groups, and lipoma/atypical lipomatous tumor (ALT) was often observed in the 2-5 cm and ≥5 cm groups.
The distribution of histological diagnoses according to the size of soft-tissue tumors.
Management and clinical outcomes. In the 2-5 cm group, all three patients who were diagnosed with a malignant tumor by needle biopsy, and two patients who were diagnosed with a benign tumor (angiofibroblastoma, and tenosynovial giant cell tumor) were referred to a specialized hospital (Kanazawa University Hospital, Kanazawa, Japan) for additional close examination and treatment. Excision of benign tumors diagnosed by needle biopsy was performed at our Institution for nine patients in the group with tumor of 2-5 cm. No histological differences were observed between the needle biopsy specimen and the excised specimen. Another five patients who were diagnosed with benign tumors by needle biopsy were monitored at an outpatient clinic because they had no symptoms or because they did not wish to undergo tumor excision. No malignant findings in the 19 excisional biopsy specimens were observed in the 2-5 cm group. The mean follow-up period for the 2-5 cm group was 7 months (range=1-58 months). No recurrence or progression was observed during the follow-up period.
Discussion
Unplanned excision of soft-tissue tumors must be avoided because residual tumor cells have the potential to proliferate and to cause recurrence or metastasis (11-14, 24-30). The risk factors for unplanned excision are reported to include tumor size of ≤5 cm, superficial tumor depth, trunk tumor location, and male sex (13, 19, 22, 24, 27-29). Regarding size, soft-tissue tumors of ≤5 cm are frequently encountered, which our finding of the rate of 78% (82/105) in the present study was in line with; however, some of these tumors are malignant, and there is a high risk of unplanned excision of such tumors. In contrast, malignant soft-tissue tumors of ≤2 cm are so rare that excisional biopsy is conditionally permitted in the 2020 guidelines; however, the management of soft-tissue tumors of 2-5 cm in size is not defined (15). Furthermore, the actual incidence of malignancy in soft-tissue tumors of 2-5 cm in size is not clear, even to the orthopedic oncologists who engage in the treatment of such tumors. Thus, this research can provide useful information about the characteristics and management of soft-tissue tumors of 2-5 cm in size.
MRI was performed for 90-100% of patients in the three groups in the present study. In all cases, the biopsy methods (excisional biopsy, n=64; needle biopsy, n=41) were selected based on the tumor size and the MRI findings. Excisional biopsy was performed for 19 out of 38 patients (50%) with soft-tissue tumors of 2-5 cm, and 39 out of 44 patients (89%) with tumors of ≤2 cm, excluding those who underwent needle biopsy due to abnormal MRI findings (e.g., heterogeneous signal intensity on T2-weighted images). In line with the strategy for soft-tissue tumors of ≤2 cm in the 2020 guidelines (15), excisional biopsy was performed even for those of 2-5 cm when the tumor was located at a superficial site away from important organs, and MRI revealed benign findings (Figure 1). Needle biopsy was performed for 19 out of 38 patients (50%) with soft-tissue tumors of 2-5 cm, and five out of 44 patients (11%) with tumors of ≤2 cm, based on the abnormal findings of MRI (6-9). In contrast, 17 out of 23 patients (74%) with tumors of ≥5 cm underwent needle biopsy based on the tumor size in line with the strategy for soft-tissue tumors of ≥5 cm in the 2020 guidelines (15), with the exclusion of six cases (lipoma/ALT, n=4; epidermal cyst, n=2) in which excisional biopsy was performed due to the lack of malignant findings on MRI and the clinical features.
A 68-year-old female patient noticed a mass on her lower back. The mass had gradually increased in size over several years without pain and the patient’s general practitioner at a medical clinic referred her to our Institution for close examination and treatment. The tumor was located on the subcutaneous layer of the lower back and the tumor size was 41 mm. The tumor was hyperintense on both T1-weighted (A, D) and T2-weighted (B) magnetic resonance imaging (MRI). The hyperintensity was completely suppressed on T2 fat-suppression MRI (C). She underwent tumor excision (E) without preoperative needle biopsy because the tumor was located at a superficial site away from important organs and MRI revealed benign findings of homogeneous lipomatous tumor. The histological diagnosis was lipoma/atypical lipomatous tumor, based on the presence of mature adipocytes of various sizes without lipoblasts or atypical stromal cells (F). Bar=100 μm.
In cases with typical benign properties on MRI (e.g., homogenous lipomatous tumor), excision without needle biopsy can be considered (Figure 1); however, in addition to imaging, a clinical evaluation was essential for deciding the strategy in that case (31). Rapid progression or painful mass is possibly a sign of malignancy; thus, a global assessment is needed in order to consider excisional biopsy. In the present study, no malignancies were observed in the patients who underwent excisional biopsy, however, further investigation is required before performing an excisional biopsy even for soft-tissue tumors measuring 2-5 cm in size with typical benign findings on MRI. In addition, referral to specialized institution as soon as the histological diagnosis of the excisional biopsy revealed malignancy was also important for avoiding treatment delays (12).
The 2-5 cm soft-tissue tumor group included three patients with high-grade malignancies (3/38; 8%). The histological subtype was leiomyosarcoma in two cases and metastatic soft-tissue tumor of carcinoma in one case. All three cases had abnormal MRI findings, including high vascularity on contrast-enhanced T1-weighted images (Figure 2) or peritumoral edema on T2-weighted images (Figure 3); thus, needle biopsy was performed to confirm the histology before treatment. In previous studies, myxofibrosarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and leiomyosarcoma have often been reported to belong to the histology of residual tumors after an unplanned excision (5, 22, 24-28, 30), and the MRI features of these diseases are important to understand in order to select the optimal treatment strategy (6-9). A needle biopsy should be considered when these soft-tissue tumors are suspected based on either their characteristic MRI findings or when other tumors are suspected based on atypical MRI findings. Soft-tissue metastasis of carcinoma is uncommon, and it has only rarely been reported (32-34). Clarifying the patient’s past medical history by interview or performing systemic computed tomography is useful for identifying primary lesions. However, when the primary site is unknown, it is essential to consult a medical oncologist or to refer the patient to a specialized institution so as not to encounter a delay in treatment (12).
A 71-year-old female patient had noticed a mass on her right thigh a few weeks previously. The tumor was a mobile, elastic hard mass with no tenderness. The patient’s general practitioner at a medical clinic referred her to our Institution for close examination and treatment. The tumor was located on the subcutaneous layer of her right thigh and the tumor size was 41 mm. The tumor appeared iso-intense on T1-weighted (A) and slightly hyper-intense on T2-weighted (B, E) magnetic resonance imaging (MRI), and hyper-intense on T2 fat-suppression MRI (C); the inside of the tumor was enhanced on contrast-enhanced MRI (D). She underwent needle biopsy due to abnormal MRI findings. The histological diagnosis was leiomyosarcoma based on the proliferation of atypical spindle cells with eosinophilic cytoplasm with interlaced bundles (F). The patient was immediately referred to a specialized institution (Kanazawa University Hospital) for further examination and treatment. Bar=100 μm.
A 66-year-old male patient had noticed a painful mass on his right buttock approximately 1 month previously. His symptom did not improve and the patient’s general practitioner at an orthopedic surgery clinic referred him to our Institution for close examination and treatment. The tumor was located on the intermuscular space between the gluteus maximus and medius and the tumor size was 30 mm. The tumor appeared iso-intense on T1-weighted magnetic resonance imaging (MRI) (A) and iso- to hyper-intense on T2 fat-suppressed MRI (B) and T2-weighted MRI (C), on which the surrounding area of the tumor was especially hyperintense. He underwent needle biopsy due to the abnormal MRI findings. The histological diagnosis was metastatic carcinoma of the soft tissue, based on the observed proliferation of atypical cells with nest-like structures (D) and positive immunohistochemical staining of AE1/AE3 (an epithelial marker) (E). He was introduced to a urologist at our Institution and was immediately referred to a specialized institution (Kanazawa University Hospital) for further examination and treatment. Bars=100 μm.
The present study was associated with some limitations. Firstly, this was a retrospective study that was performed at a single institution with a relatively small number of cases. Secondly, general practitioners often referred patients with soft-tissue tumors of ≥5 cm directly to specialized hospitals because malignancy was suspected due to the size; thus, the characteristics and the histological subtypes in the group with tumor ≥5 cm were relatively limited in the present study. Thirdly, the follow-up period was relatively short. Most patients who underwent tumor excision for benign tumors opted to stop regular hospital visits because they usually had no symptoms. However, it was always explained that the patient should revisit our institution or consult a nearby doctor when they noticed swelling, pain, or the re-appearance of a mass after surgery. Fourthly, fluorescence in situ hybridization was not available for determining the histological diagnosis in our institution. Differentiation of lipoma and ALT by hematoxylin-eosin staining or immunohistochemical staining alone is not easy, however, these techniques were applied to diagnose high-grade malignancy (dedifferentiated liposarcoma).
In conclusion, some malignancies were detected among soft-tissue tumors of 2-5 cm in size (3/38; 8%). In order to avoid unplanned excision, it is important to consider needle biopsy when abnormal MRI findings are detected.
Acknowledgements
The Authors thank Hiroko Ikeda for performing histological examination of all the specimen. In addition, we thank the other past and present members of our Department for their work.
Footnotes
Authors’ Contributions
HT, NY, and YA contributed to conceptualization. YA carried out data curation, formal analysis, and investigation. TM, HK, TO, SS, TK, DI, TH, KA and YT provided assistance for data curation and resources. TM, HK, TO, SS, TK, DI, TH KA, and YT conceived methodology and contributed to project administration and supervision. HT, NY and YA contributed to the validation and visualization. YA analyzed all the patient data using software and wrote the original draft preparation. All Authors read, reviewed, edited, and approved the final article.
Conflicts of Interest
The Authors declare no conflicts of interest in association with the present study. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
- Received January 10, 2022.
- Revision received February 4, 2022.
- Accepted February 7, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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