Metastatic multicentric epithelioid angiosarcoma of bone. A case report with pitfalls. Tumor seeding after percutaneous biopsy and hypercalcemia

doi:10.21203/rs.3.rs-3237839/v1

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Case Report

Metastatic multicentric epithelioid angiosarcoma of bone. A case report with pitfalls. Tumor seeding after percutaneous biopsy and hypercalcemia

https://doi.org/10.21203/rs.3.rs-3237839/v1

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BACKGROUND: Angiosarcomas are a type of malignant tumor of vascular origin. They represent less than 1% of all primary bone tumors. The multicentric or metastatic does not differ in its high aggressiveness and poor prognosis.

CASE PRESENTATION: We describe a case of an elderly male with bone angiosarcoma initially located in proximal femur. After biopsy in a non-expert sarcoma center, he presented a tumor involvement in the path of the needle, in additional finding of multicentric/metastatic that involve the sacro-coccygeal level assessed by magnetic resonance imaging. He associated tumoral hypercalcemia secondary to malignancy and was referred to our sarcoma center for therapeutic decision. He was treated by tumoral resection and reconstruction with proximal femur tumor prosthesis due to high risk of pathological fracture. In the early follow-up he presented pulmonary metastasis and new sarcoma implants in soft parts, dying a few months later.

CONCLUSIONS: Multicentric and/or metastatic epithelioid angiosarcomas require diagnostic and therapeutic thoroughness to improve the patient's quality of life and survival. Percutaneous biopsies have a risk of tumor seeding in the needle trajectory; therefore, they must be performed in centers with expertise in sarcomas. At present, multicentric or metastatic bone involvement is only of theoretical relevance since the treatment and prognosis are identical. Despite that hypercalcemia in sarcomas is a rare problem, the case has this peculiarity, and we highlight its investigation in some of these cases.

Angiosarcoma

multicentric

metastasis

core needle biopsy

hypercalcemia

tumor seeding

Angiosarcomas are a high-grade malignant neoplasm with endothelial differentiation [1]. Although they can arise in virtually any organ of the body, bone tissue involvement is extremely rare, about 3.6% of all angiosarcomas [2].

It appears more frequently in adults [3–4]. In most cases they are single tumors, but sometimes they present as a multifocal disease, which can be difficult to distinguish from bone metastases [3, 5–6]. They are particularly aggressive with a high rate of lymph node involvement and local recurrence [7]. The delay in diagnosis is usually due to its insidious growth, in which biopsy becomes the last step of certainty for histological and immunohistochemical analysis [7–9]. Core needle biopsy (CNB) is the most used technique in sarcoma centers [10] and its treatment is mainly surgical [3–4].

In this illustrative case of multicentric bone angiosarcoma with subsequent pulmonary metastasis we analyze the possible reasons of its dissemination during the diagnostic process after percutaneous biopsy. In addition, a review of this rare tumor is made.

A 72-year-old male with no personal history of interest debuted three months earlier with symptoms of pain in the proximal region of the left thigh without associated trauma. The pain increased until it prevented him from walking, at which time he went to the emergency department where a pelvis plain radiography was performed.

The radiological image showed an osteolytic lesion that had destroyed the intertrochanteric region of the left femur (Fig. 1A). A computed tomography (CT) was performed and showed the femur lesion with an associated soft tissue mass (Fig. 1B). In the staging studies, other detectable metastases were ruled out.

Due to the intense pain, he was admitted to hospital. During admission he presented hypercalcemia (maximum corrected calcium level, 14.5 mg/dL) with sampled levels of PTH and 1,25(OH)2D both suppressed and elevated parathyroid hormone related peptide (PTHrP). The ionic disorder was treated by the internal medicine team, who ruled out hyperparathyroidism and the etiology were considered to be hypercalcemia of malignancy due to osteolytic lesion and humeral mechanism (HHM). In order to obtain a sample of the bone lesion, a percutaneous CNB was performed in the region posterior to the greater trochanter with a pathological diagnosis of angiosarcoma. He was subsequently referred to our sarcoma center for a therapeutic decision.

Physical examination revealed pain throughout the proximal third of the femur, on passive and loaded rotations. Selective pain was felt in the sacro-coccygeal region. There were no skin alterations except for the biopsy scar, no signs of complication and no distal neurovascular involvement.

Considering the high risk of pathological fracture with 12 points on the Mirels scale [8], the surgical treatment was indicated after evaluation by the Bone and Soft Tissue Tumors Committee (BSTTC).

Bone scintigraphy of the entire skeleton with Tc99 and SPECT-CT of the pelvis (Fig. 2) and magnetic resonance imaging (MRI) was performed for surgical planning (Fig. 3A-C). Imaging confirmed findings compatible with angiosarcoma of the proximal femur with metastatic/multicentric involvement in the sacrococcygeal region.

In addition, an intramuscular soft tissue mass located in the left gluteus maximus not detected in the CT scan prior to the percutaneous biopsy, shows a probable tumor seeding in the trajectory towards the sacral region (Fig. 3D).

Wide intra-articular tumor resection of the proximal femur and reconstruction with tumor prosthesis and bipolar head were indicated (Fig. 4).

A left proximal femoral resection was received in the Pathology Department (Fig. 5A-C). No macroscopic tumoral invasion of surgical margin was observed. On sectioning, a lateral proximal metaphysis-diaphyseal tumor with soft tissue extension was seen (Fig. 5C). Histopathologically the tumor contained a densely cellular proliferation that formed vascular channels. The cells were large with abundant eosinophilic cytoplasm, high nuclei-cytoplasmatic ratio and prominent nucleoli (Fig. 5D). Marked atypia and abundant typical and atypical mitotic figures were observed (Fig. 5D). Tumoral cells revealed positive immunostaining to vascular markers (CD34 (Clone QBEnd-10, RTU, Agilent-Dako), CD31 (Clone JC70A, RTU, Agilent-Dako), ERG (Clone EP111, RTU, Agilent-Dako) (Fig. 5E) and XXXodoplanin (Clone D2-40, RTU, Agilent-Dako)). Cell proliferation index (Ki67 [clone MIB-1, RTU, Agilent-Dako]) was approximately 40%. The diagnosis of epithelioid angiosarcoma of bone was made.

After surgery, the BSTTC decided on a new MRI and PET-CT to further evaluate the sacrococcygeal lesions suggestive of metastasis or multifocal disease and possible tumor remnants. A nodule compatible with pulmonary metastasis was identified (Fig. 6A). Other similar metastases were also observed adjacent to the gluteus maximus and in the anterior rectus muscle (Fig. 6B-C).

Adjuvant therapies were not indicated by the BSTTC due to progressive clinical deterioration. With these results, a palliative care in his community from his referral hospital was assessed at the request of the patient and family, and he died two months after surgery.

Angiosarcomas are extremely rare primary bone tumors that accounts less than 1% of all malignant bone tumors [1]. It mainly affects the long bones, femur and tibia being the most frequently affected, followed by the axial skeleton. It presents two peaks of incidence in the second and seventh decade of life [3, 5].

Tumor-induced hypercalcemia is a relatively common complication of certain types of cancer, but has rarely been described in sarcoma patients [11]. The most common mechanism is HHM resulting from overproduction of PTHrP. It is estimated that approximately 80% is mediated by HHM, while almost 20% is the result of local osteolytic hypercalcemia. The most frequent hypercalcemia secondary to osteolysis is secondary to bone metastasis in breast cancer, multiple myeloma and lymphoma and in HHM are squamous-cell cancer and gynecological tumors [12]. In our case, both mechanisms are involved. Regardless of the mechanism hypercalcemia in sarcomas is a rare disorder, which highlights the peculiarity of this tumor [13–14].

Therapeutic options in angiosarcomas are scarce and are mainly based on surgical treatment [4–5]. Life expectancy can be increased with early diagnosis and optimal surgery, which is not always possible [3]. CNB is the most commonly used technique in sarcoma centers [10]. This allows for a histological and immunohistochemical study essential for diagnosis [7–9].

In the case presented, the initial biopsy performed generated a plausible tumor dissemination, this fact being demonstrated both in the imaging tests and in the anatomopathological samples of the biopsy tract. Traditionally, in musculoskeletal oncology, it was assumed that the biopsy tract should be resected along with the tumor. Moreover, it has been described that recurrence-free survival is greater in patients without tumor seeding despite resection. According to Barrientos et al 107 months free of local recurrence compared to 11 months [15].

CNB should be performed by radiologists specialized in musculoskeletal pathology using a coaxial technique [16]. The location of the biopsy area has to be discussed with the orthopedic oncology surgeon according to the surgical approach to be performed. In the case of the proximal femur, it is generally performed over the greater trochanter, avoiding the posterior approach in which the thickness of the gluteal muscles must be crossed. Therefore, the lateral approach would probably have simplified access and reduce the risk of muscle contamination, favoring subsequent surgery for resection of the proximal femur [16].

Diagnosis of angiosarcoma is based on its histopathological and immunohistochemical findings which consist of vascular channels lined by marked atypical cells and endothelial markers immunoreaction [7–9]. Other high-grade tumors such as metastatic carcinoma or metastatic melanoma may present differential diagnosis problems in some cases. Carcinomas may also present vascular channels and cytokeratin positivity, but these vascular channels are not well formed nor lined by tumoral atypical cells, and do not show vascular markers immunoreactivity. Metastatic melanoma may also present hemorrhagic areas, but is positive for melanic markers and negative for vascular markers.

In the case described, the patient had a multifocal angiosarcoma or bone metastasis at diagnosis which greatly limited his survival. We think that multifocal bone angiosarcomas may be worth reevaluating the entity in light of the current case.

In case descriptions, it is very difficult to know whether a patient with multiple lesions are metastases or a multifocal tumor, and this leads us to question the relevance of the multifocal bone angiosarcoma entity described in the literature and to suggest instead that the other lesions were metastases from a primary angiosarcoma. These findings highlight the rationale for whole-body diagnostic staging in this type of tumor, but we do not believe that they change the poor clinical course of the disease. Thariat et al. indicate that in the presence of an angiosarcoma diagnosed as multifocal, the bone lesions may be metastases from an occult primary angiosarcoma, justifying a whole-body diagnostic workup [6]. This analysis is consistent with that provided by Palmerini et al, who evaluate multifocal bone lesions and metastases interchangeably [5]. Therefore, this discussion has only theoretical relevance in our case.

The aim of the surgery was to improve the quality of life and avoid a possible pathological fracture of the femur, discouraging the resection at the sacrococcygeal level and therefore of the biopsy tract since his prognosis was not going to change. In addition, he was later diagnosed with pulmonary metastasis, a fact that is observed with relative frequency in this type of tumors where it appears in up to 32% of cases, with around 19% of them having pulmonary involvement [3].

Multicentric or metastatic epithelioid bone angiosarcomas are very rare tumors, but with a high aggressiveness and poor prognosis. They require diagnostic and therapeutic thoroughness to improve the patient's quality of life and survival.

Percutaneous biopsies have a risk of tumor seeding in the needle trajectory, so it is advisable to perform them in expert centers. The different aspects such as the approach must be evaluated to guarantee maximum success in the diagnostic-therapeutic process.

Core needle biopsy (CNB)

Humeral hypercalcemia of malignancy (HHM)

Computed tomography (CT)

Parathyroid hormone related peptide (PTHrP).

Magnetic resonance imaging (MRI)

Bone and Soft Tissue Tumors Committee (BSTTC)

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Informed consent was obtained according to national and institutional guidelines. Written informed consent was obtained from the participants for publication of the details of their medical case and any accompanying images. The study was conducted according to the Declaration of Helsinki

CONSENT FOR PUBLICATION

The patient provided written informed consent that the data concerning his case would be submitted for publication.

AVAILABILITY OF DATA AND MATERIALS

All data generated or analyzed during this study are included in the article. Further inquiries can be directed to the corresponding authors

COMPETING INTERESTS

The authors declare no competing interests

FUNDING

This research has received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

AUTHORS' CONTRIBUTIONS

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jorge Fuentes-Sánchez. The first draft of the manuscript was written by Jorge Fuentes-Sánchez and Eva Manuela Pena-Burgos and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

ACKNOWLEDGEMENTS

Not applicable

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No competing interests reported.

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Metastatic multicentric epithelioid angiosarcoma of bone. A case report with pitfalls. Tumor seeding after percutaneous biopsy and hypercalcemia

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INTRODUCTION

CASE PRESENTATION

DISCUSSION

CONCLUSIONS

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