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J Adv Res. 2016 July; 7(4): 581–587.
Published online 2016 February 2. doi:  10.1016/j.jare.2016.01.003
PMCID: PMC4921935

Bone and soft tissue sarcomas during pregnancy: A narrative review of the literature

Graphical abstract

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Keywords: Cancer, Pregnancy, Bone sarcomas, Soft tissue sarcomas

Abstract

Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing’s sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence.

Introduction

Cancer and pregnancy

Cancer diagnosis during pregnancy is a rare coexistence in a ratio of one case per 1000 deliveries. However, there is an increasing trend due to delaying pregnancy in western societies into the later reproductive years [1].

The most common gestational cancers are those appearing during the reproductive period of a woman. Breast cancer and cervical cancers are the most frequently diagnosed malignancies followed by hematological tumors and melanoma [1].

Diagnostic and staging workup should be very carefully performed due to maternal and fetal radiation exposure. Recommendation of imaging studies should always follow the established guidelines [2].

Systemic chemotherapy should be avoided during the first trimester of pregnancy due to lethal, teratogenic or developmental malformation effects. However, during the second and third trimesters certain chemotherapeutic drugs can be administered. Hormonal and/or targeted treatments should not be advised. In addition, radiotherapy cannot be applied to the mother’s trunk due to the lethal effects on the fetus [3], [4].

Metastatic transmission to the products of conception happens rarely and the most frequent malignancies that invade placenta and fetus are melanoma (30%), cancer of unknown primary site (22.5%), hematological malignancies (15%), breast cancer (14%) and lung cancer (13%) [5].

Bone and soft tissue sarcomas [6]

Malignant bone tumors are rare, accounting for only 0.2% of all malignancies. Among them the most frequent are osteosarcoma, Ewing’s sarcoma and chondrosarcoma. Less frequent sarcomas are the malignant fibrous histiocytoma, chordoma, and very rarely liposarcoma, angiosarcoma, and hemangiopericytoma.

Bone osteosarcoma

It is the commonest primary bone tumor and occurs predominantly in adolescence with a peak incidence at the age of 15–19 years. Osteosarcoma most commonly involves long bones (mainly the tibia close to knee joint) and more rarely the axial skeleton. It presents with localized bone pain characteristically during the night or at rest. Limb-sparing surgery with extending endoprostheses is the treatment of choice. Adjuvant chemotherapy improves overall survival. In certain cases neoadjuvant chemotherapy can be used.

Ewing’s sarcoma

It is part of the Ewing’s sarcoma family including also the primitive neuroendocrine tumor and Askin’s tumor. The median age is 14 years and tumor affects long bones or axial skeleton. Presenting symptoms are local pain, (deteriorating at night) as well as fever or weight loss. Systemic chemotherapy (neoadjuvant or adjuvant) is usually followed by local radiotherapy. In certain cases, surgery can be recommended following induction chemotherapy.

Chondrosarcoma

It is more commonly diagnosed over the age of 40. Most frequently it affects the pelvis, axial skeleton and proximal limbs. Histologic grading is important ranging from grade 1 to 3. The primary modality of therapy is surgery. Five-year survival is >90% and 25% for grade 1 and 3, respectively.

Soft tissue sarcomas

Leiomyosarcoma

The most common site of leiomyosarcomas is the retroperitoneum (50%), followed by abdominal viscera, uterus or extremities. Retroperitoneal leiomyosarcomas usually present with vague abdominal discomfort, abdominal mass or weight loss, while peripherally located primaries present with a painless enlarging mass. Surgery remains the dominant treatment. Chemotherapy has poor results in metastatic disease.

Liposarcoma

It affects adults between 40 and 60. It involves most commonly the thigh followed by abdominal cavity. Histologically, there are four types: well-differentiated, myxoid, pleomorphic and dedifferentiated liposarcoma. Prognosis is dependent on histologic type and site of disease.

Rhabdomyosarcoma

They arise from skeletal muscle cells. The most common locations are in the head and neck (40%), the genitourinary tract (25%) and the extremities (20%). The symptoms are associated with the tumor location. There are two main histologic types: the embryonic and the alveolar type.

GIST (Gastrointestinal stromal tumors)

GISTs are soft tissue mesenchymal tumors occurring in the gastrointestinal tract, originating in the interstitial cells of Cajal. The annual incidence in UK ranges from 1.32 to 1.50 per 100,000 population which is equivalent to 800–900 new cases per year. The stomach (60%) and small intestine (30%) are the most common primary sites followed by duodenum (5%) and colorectum (5%). The most common symptoms are vague, nonspecific abdominal pain and discomfort. Rarely GI obstruction or bleeding could be seen.

Surgery is the primary treatment, whereas targeted therapy with tyrosine kinase inhibitors (imatinib, sunitinib or regorafenib) produced excellent results in both adjuvant and metastatic settings.

Synovial sarcoma

It can occur at any age but it is more common among teenagers and young adults. Most commonly it is located in the legs or arms. It is usually diagnosed as a slowly growing painless mass. Surgery followed by radiotherapy is the recommended treatment. Chemotherapy is advised in patients with metastatic disease.

Kaposi’s sarcoma

Is a sarcoma caused by human herpesvirus 8. It is classified into four different forms: the classic, the endemic, the immunosuppression – associated and AIDS-associated Kaposi sarcomas. It involves the skin, mouth, GI tract and respiratory tract. In general, surgery is not recommended.

Angiosarcoma

It most commonly occurs in the skin, breast, liver, spleen and deep tissue. It can present as a skin lesion or a painless soft lump. Surgery is the primary therapeutic choice.

Endometrial stromal sarcoma (EDS)

EDSs are very rare malignant tumors that make up approximately 10% of uterine sarcomas but only around 0.2% of all uterine sarcomas. They can present by abnormal bleeding or spotting, vaginal discharge, pelvic pain or mass. Histologically, EDSs are divided into the following: (a) endometrial stromal nodule, (b) low-grade endometrial stromal sarcoma and (c) undifferentiated stromal sarcoma. Surgery with adjuvant radiotherapy is the recommended treatment. Five-year survival for early stage I is 54–100%, for stage II (30%) and for stage III–IV only 11%.

Literature search

Bone sarcomas (Table 1)

Table 1
Bone sarcomas during pregnancy.

Osteosarcoma

In total 24 cases of various subtypes of gestational osteosarcomas have been reported since 1977. Osteoblastic, fibroblastic, chondroblastic, paraostal or high-grade osteosarcomas have been documented. The most common primary bone sites were thigh, pelvis and back, whereas the most frequent presenting symptoms were pain, detection of a mass or pathological fracture. Most patients were treated surgically either during pregnancy or postpartum and some patients received chemotherapy in an adjuvant setting during the postpartum period. Survival outcomes are similar to their nonpregnant counterparts [7], [8], [9], [10], [11], [12].

Ewing’s sarcoma

Since 1963 19 cases of gestational Ewing’s sarcomas have been published in the English literature, including three cases of extra-skeletal Ewing’s sarcoma. Almost all cases were diagnosed during pregnancy. Most cases were treated during pregnancy with chemotherapy, radiotherapy to the extremity and/or surgery and resulted in a favorable outcome for both mother and newborn. Only two patients underwent termination of pregnancy [10], [13], [14], [15], [16], [17], [18].

Chondrosarcoma

Only 10 cases of gestational chondrosarcomas appeared in the literature during the last 25 years. Primary tumors were located on iliac, innominate, tibial head and maxillary bones. One case was diagnosed as extraskeletal myxoid chondrosarcoma. Surgical intervention during pregnancy is not always feasible [9], [10], [19], [20].

Soft tissue sarcomas (Table 2)

Table 2
Soft tissue sarcomas during pregnancy.

Leiomyosarcoma

Gestational leiomyosarcoma constitutes 12% of all sarcomas diagnosed during pregnancy. Since 1969, 17 cases have appeared in the literature. Among the reported cases most of them arise in the uterus followed by vulva, jejunum and retroperitoneal area. Histopathologically, typical leiomyosarcomas (mostly high grade), or epithelioid or myxoid type was diagnosed. Uterine leiomyosarcomas are generally considered to be more aggressive than other types of uterine tumors [9], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34].

Liposarcoma

During the last two decades 17 cases of liposarcomas during pregnancy (12%) have been published. Almost all of them were located in the retroperitoneal area mostly with myxoid histology. Surgical manipulation is not feasible in all patients. About 50% of patients died early after diagnosis, while newborns remained well and healthy wherever deliveries were achievable [10], [29], [35], [36], [37], [38], [39], [40], [41], [42], [43].

Rhabdomyosarcoma

Fourteen cases of gestational rhabdomyosarcoma (10%) have been described during the last 45 years. Most common primary sites were orbit or vagina followed by maxillary sinus, nasal septum, perineum, bladder, breast or retroperitoneum. Apart from typical rhabdomyosarcomas some patients were diagnosed with embryonal, botryoid, spindle-cell or alveolar subtype of rhabdomyosarcomas. In one case invasion of the placenta was found [10], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56].

Gastrointestinal stromal sarcoma (GIST)

Since the term of GIST was given in 1983, 9 pregnant mothers with gestational GIST have been documented. Signs and symptoms are usually non-specific unless they occur as a result of the “mass effect” of the tumor itself. CT scans are not recommended, however they can be replaced by abdominal ultrasound or even MRI. The optimal timing of surgery it is not well defined leaving the decision to the multidisciplinary team setting although it is considered safe in pregnancy. Imatinib treatment during pregnancy or breast feeding is contra-indicated since spontaneous miscarriages and birth defects have been reported. Prognosis of women with gestational GIST remains favorable [57], [58], [59], [60], [61], [62], [63], [64], [65].

Synovial sarcomas

Gestational synovial sarcomas are rare sarcomas. Since 2007 only 9 cases (7%) of synovial sarcomas during pregnancy were found. Three were primary pulmonary sarcomas, two head and neck sarcomas, one leg, one pelvis, one abdominal wall and one renal synovial sarcoma. Signs and symptoms included local slowly growing swelling for superficial tumors or symptoms related to the primary sites i.e. dyspnea, hematuria. Most women died of advanced disease [29], [66], [67], [68], [69], [70], [71], [72].

Kaposi’s sarcoma

Eight cases (6%) of Kaposi’s sarcomas were found in the literature during the last 40 years. Five cases were diagnosed as AIDS-associated Kaposi’s sarcomas following maternal infection with human immunodeficiency virus [73], [74], [75], [76], [77], [78], [79], [80].

Angiosarcoma

Only 5 gestational angiosarcomas were reported in the English literature. Two were located to the breast and one to the skull. No data are available for the other two patients [9], [81], [82], [83].

Endometrial stromal sarcoma

Five cases (4%) have been reported between 2002 and 2014. Most of them represent low-grade stromal sarcomas [85], [86], [87], [88].

Conclusions

In conclusion, diagnosis of bone and soft-tissue sarcomas in young pregnant women is rare. However, almost all types of sarcomas have been reported to coexist with pregnancy. In localized disease the goal is to treat primarily the mother and simultaneously to try to protect and safe the life of the fetus depending on the period of gestation. In metastatic disease the prognosis of the mothers is still poor in majority of the cases.

Conflict of Interest

The authors have declared no conflict of interest.

Compliance with Ethics Requirements

This article doesnot contain any studies with human or animal subjects.

Biographies

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George Zarkavelis, MD, is a fellow in Medical Oncology, Department of Medical Oncology, Ioannina University Hospital, Greece.

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Dimitrios Petrakis, MD, PhD, works as a Senior Oncologist, Department of Medical Oncology, Ioannina University Hospital, Greece

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George Fotopoulos, MD, works as a Senior Oncologist, Department of Medicine, Sotiria Hospital, University of Athens, Greece.

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Sotirios Mitrou, MD, works as a Senior obstetrician and gynecologist, REA Maternal Hospital, Athens, Greece

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Nicholas Pavlidis, MD, PhD, FRCP Edin, is a Professor and Head of the Department of Medical Oncology, Ioannina University Hospital, Greece,and Member of Scientific Committee and Coordinator of Master classes of European School of Oncology; Member of Scientific Committee of ESMO/ASCO Global Curriculum;and Editor in Chief, Cancer Treatment Reviews.

Footnotes

Peer review under responsibility of Cairo University.

figure fx1

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