Locally Aggressive Connective Tissue Tumors

Abstract

In this review, we highlight the complexities of the natural history, biology, and clinical management of three intermediate connective tissue tumors: desmoid tumor (DT) or aggressive fibromatosis, tenosynovial giant cell tumor (TGCT) or diffuse-type pigmented villonodular synovitis (dtPVNS), and giant cell tumor of bone (GCTB). Intermediate histologies include tumors of both soft tissue and bone origin and are locally aggressive and rarely metastatic. Some common aspects to these tumors are that they can be locally infiltrative and/or impinge on critical organs, which leads to disfigurement, pain, loss of function and mobility, neurovascular compromise, and occasionally life-threatening consequences, such as mesenteric, bowel, ureteral, and/or bladder obstruction. DT, PVNS, and GCTB have few and recurrent molecular aberrations but, paradoxically, can have variable natural histories. A multidisciplinary approach is recommended for optimal management. In DT and PVNS, a course of observation may be appropriate, and any intervention should be guided by symptoms and/or disease progression. A surgical approach should take into consideration the infiltrative nature, difficulty in obtaining wide margins, high recurrence rates, acute and chronic surgical morbidities, and impact on quality of life. There are similar concerns with radiation, which especially relate to optimal field and transformation to high-grade radiation-associated sarcomas. Systemic therapies must be considered carefully in light of acute and chronic toxicities. Although standard and novel therapies are promising, many unanswered questions, such as duration of therapy and optimal end points to evaluate efficacy of drugs in clinical practice and trials, exist. Predictive biomarkers and novel clinical trial end points, such as volumetric measurement, magnetic resonance imaging T2 weighted mapping, nuclear imaging, and patient-reported outcomes, are in development and will require validation in prospective trials.

Fig 1.

Desmoid tumor. (A) X-ray of a lower extremity that demonstrates a radiolucent mass. (B) Large protuberant mass that involves the ankle joint. (C) Gross appearance of resected mass. (D) Section of a grossly resected desmoid tumor that show a smooth, glistening white tumor with trabeculations. (E) Hematoxylin and eosin stain that shows uniform elongated spindle cells in a collagenous matrix (magnification, 200×). Panels D and E are courtesy of Meera Hameed, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Fig 2.

Giant cell tumor of bone. (A) Computed tomography scan of an infiltrative mass that involve the sacrum. (B) Osteoclast-like giant cells in a syncytial growth pattern with interspersed mononuclear cells (magnification, 200×). Images courtesy of Robert Lefkowitz, MD, Department of Radiology, and Meera Hameed, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Fig 3.

Pigmented villonodular synovitis.(A) Axial T1-weighted magnetic resonanceI image that shows lobulated PVNS (red line) throughout joint and extensive subjacent erosions of femoral condyles (white outline). (B) Sagittal T2 fat-saturated magnetic resonance image that shows a multilobulated intra-articular mass abutting the posterior cruciate ligament, tibial plateau, and posterior knee joint capsule. (C) Intraoperative imaging that shows a brownish pigmented mass. (D) Gossly resected specimens that show multiple yellowish to brown masses with no encapsulation. (E) Randomly distributed multinucleated osteoclast-like giant cells accompanied by mononuclear cells, histiocytes, and hemosiderin-laden macrophages (black arrows; magnification, 200×). Images courtesy of David Panicek, MD, Department of Radiology, Meera Hameed, MD, Department of Pathology, and Nicola Fabbri, MD, Department of Orthopedic Oncology Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.

Fig 4.

Challenges in accurate imaging of tumors to access efficacy of drugs. (A) Baseline pretreatment magnetic resonance imaging (MRI) scan shows high T1 signal indicative of an active, cellular tumor. (B) Post-sorafenib MRI scan that shows a minimal decrease in tumor size but a significant decrease in T1 signal, which suggests a decrease in cellularity and an increase in collagen or tissue scarring.

Fig 5.

Treatment response. Positron emission tomography (PET)/computed tomography (CT) scan of giant cell tumor of bone (A) at presentation (ie, baseline) and (B) after 8 weeks of denosumab, which shows minimal decrease in size but significant decrease in fluorodeoxyglucose (FDG) avidity. (C) A deep mesenteric and abdominal desmoid tumor (C) at baseline experienced (D) a dramatic response to sequential sorafenib (5 weeks, discontinued for hypertension) followed by liposomal doxorubicin (two cycles). PET/CT of recurrent pigmented villonodular synovitis (E) at presentation and (F) after 3 months of imatinib that shows significant decrease in tumor size and FDG avidity. Images courtesy of David Thomas, MBBS, PhD, Garvan Institute of Medical Research, Darlinghurst, Australia; Robert Lefkowitz, MD, Department of Radiology, and Marylou Keohan, MD, Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; and Vinod Ravi, MD, Department of Medical Oncology, MD Anderson Cancer Center, Houston, TX.