Inflammatory myofibroblastic tumor of the mesentery: a clinical dilemma

Although rare, extra-pulmonary inflammatory myofibroblastic tumors (IMTs) are becoming increasingly recognized. While surgical resection is currently an effective and accepted treatment for IMTs, the optimal management of unresectable or residual IMTs remains a clinical dilemma. We present the case of an incompletely resected IMT treated successfully with anti-inflammatory therapy alone, and describe the rationale for this approach.     

Chromoplectic TPM3–ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib

BackgroundInflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRβ fusions and may benefit from targeted therapy.Patient and methodsWe sought to understand the genomic abnormalities of a patient who presented for management of metastatic IMT after progression of disease on crizotinib and a significant and durable partial response to the more potent ALK inhibitor ceritinib.ResultsThe residual IMT was resected based on the recommendations of a multidisciplinary tumor sarcoma tumor board and analyzed by whole-genome mate pair sequencing. Analysis of the residual, resected tumor identified a chromoplectic TPM3–ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR.ConclusionsIn our analysis of the treatment-resistant, residual IMT, we identified a complex pattern of genetic rearrangements consistent with chromoplexy. Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs. Furthermore, this patient's remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib for patients with metastatic or unresectable IMT and ALK mutations.     

Curative liver resection for metastatic breast cancer.

AIMS: Hepatic resection is a standard procedure in the treatment of colorectal liver metastases. Liver metastases are frequent in breast cancer, but resectional treatment is rarely possible and few reports have addressed the results of surgical treatment for metastatic breast cancer. The aim of our study was to analyse the outcome of patients with metastatic breast cancer after resection of isolated hepatic secondaries and possibly to identify selection criteria for patients who may benefit from surgery. METHODS: Between 1984 and 1998, 90 patients with a history of breast cancer and suspected liver metastases were referred for surgical evaluation. Fifty-four patients also had extrahepatic disease or metastases from another primary tumour; multiple liver metastases were not amenable to surgical treatment in 20 patients. Five patients were treated by regional chemotherapy via an intra-arterial port catheter; after liver resection two patients were found to have liver metastases from intercurrent colorectal cancer. Thus only nine liver resections for metastatic breast cancer could be performed with curative intent. RESULTS: No patient died post-operatively after liver resection. In the follow-up period, four of the nine patients who were treated with curative intent received systemic chemotherapy. At a median follow-up of 29 months, four patients died from tumour recurrence. Five patients are currently alive. Five-year survival in the resection group was calculated as 51% (Kaplan-Meier estimate). Node-negative primary breast cancer and a long interval between treatment of the primary and liver metastases appeared to be associated with long survival after liver resection. CONCLUSIONS: These observations suggest that careful follow-up and adequate patient selection could offer some patients with isolated liver metastases from breast cancer a chance of long-term survival.     

Inflammatory myofibroblastic tumor: molecular landscape,targeted therapeutics,and remaining challenges

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor of intermediate malignant potential that predominantly affects children, adolescents and young adults. IMT has a predilection for the lung, abdomen, pelvis, and retroperitoneum, however, can affect any part of the body. IMT is typically localized, and multifocal or metastatic disease is uncommon. Complete surgical resection is the treatment of choice when feasible. There is no established standard of care for unresectable and advanced IMT. Approximately half of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, and fusions involving ROS1, PDGFRβ, RET and NTRK have also been described. Given the molecular landscape of IMT, management of these tumors has evolved to include tyrosine kinase inhibitors and novel targeted therapeutics. This review highlights the molecular characteristics, evolution of targeted therapies and the remaining challenges in the management of IMT.     

Primary soft tissue sarcoma of the breast

Opinion statement Primary soft tissue sarcoma (STS) of the breast is a rare and heterogeneous disease. The rarity of this tumor limits most studies to small retrospective case reviews and case reports. The optimal treatment of primary STS of the breast can best be determined through multidisciplinary discussions prior to the initiation of therapy. Whether chemotherapy is indicated is primarily determined by tumor size. There is evidence that tumors larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis [1-3]. Negative surgical margins are more important for local recurrence and overall survival than is the extent of surgical resection [1]. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumor and help obtain negative surgical margins. After surgical resection, patients with chemosensitive tumors should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Patients with tumors less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Radiation therapy should be used to improve local control in cases in which the tumor is larger than 5 cm and in cases with positive surgical margins [4-6]. The appropriate treatment of primary STS of the breast requires a multidisciplinary approach necessitating experienced surgeons, pathologists, radiotherapists, and medical oncologists.     

Inflammatory myofibroblastic tumors

INTRODUCTION: Inflammatory myofibroblastic tumors (IMT) while uncommon may arise within numerous organs. Historically, the literature regarding IMT has been confined to small one organ case series, with few reviews encompassing multiple anatomic sites, and little data regarding adjuvant treatment. METHODS: A review of patients with IMT treated at two large academic medical centers over a 15-year period was undertaken. Patient demographics, pathologic diagnoses, and pertinent clinical data were obtained. RESULTS: Forty-four cases of pathologically confirmed IMT were identified. Tumor locations included multiple anatomic sites. Therapies included complete resection, incomplete resection, observation, or chemotherapy, and/or radiation. Five patients underwent adjuvant chemotherapy and/or radiation therapy following surgery (14%) for local aggressiveness of the tumor, invasion, positive margins, or location of tumor that was not amenable to surgical resection. A second, concomitant, histologically distinct, neoplasm was identified in five cases. Of the patients who underwent treatment three local recurrences were noted (8%) and occurred in patients with partial resection without adjuvant chemo- or radiotherapy. CONCLUSIONS: Inflammatory myofibroblastic tumors may be a locally aggressive and destructive neoplasm. Tumor recurrence is unusual following complete surgical resection or organ-preserving combined modality therapy.     

Diagnosis and management of primary breast sarcoma

Primary sarcoma of the breast is an extremely rare and heterogeneous disease. The rarity of this tumour limits most studies to small retrospective case reviews and case reports and has made clinicopathological study difficult. This article reviews the current literature on the diagnosis and management of breast sarcoma. The optimal treatment of breast sarcoma involves a multidisciplinary team prior to the initiation of treatment. Patients with tumours less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Negative surgical margins are more important for local recurrence and overall survival than the extent of surgical resection. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumour and help obtain negative surgical margins. Whether chemotherapy is indicated is primarily determined by tumour size. There is evidence that tumours larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis. After surgical resection, patients with chemosensitive tumours should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Radiation therapy should be used to improve local control in cases in which the tumour is larger than 5 cm and in cases with positive surgical margins. We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. The appropriate treatment of breast sarcoma requires a multidisciplinary team approach necessitating experienced sarcoma surgeons, pathologists, radiotherapists and medical oncologists. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival.     

Unusual early recurrence of a cerebellar pilocytic astrocytoma following complete surgical resection

Summary Pilocytic cerebellar astrocytomas are usually benign tumors with generally an excellent prognosis following complete surgical resection. The goal of surgery is total resection to minimize the risk of recurrence. In this case report, a 5-year old boy who had undergone total resection of a posterior fossa pilocytic cerebellar astrocytoma (as documented by a contrast-enhanced computed tomography (CT) scan within 24 hours following surgery), developed a massive recurrence of the tumor within four months. Both the initial histology and the sections examined after the second resection revealed features typical for a pilocytic astrocytoma with no suspicion of malignancy. This case is unusual in that it is contrary to other reports suggesting that CT-documented complete surgical resection of pilocytic astrocytomas is without recurrence, and suggests the need for vigilant radiographic and clinical follow-up of these patients even if apparent complete resection of the tumor has been achieved.     

Clinical characteristics and outcomes of 17 cases of inflammatory myofibroblastic tumor at a University Hospital in China

The aim of the present study was to explore the clinical and pathological characteristics, diagnosis, and treatment of inflammatory myofibroblastic tumor (IMT). A total of 17 patients with IMT diagnosed between July 2010 and February 2020 were included in the present study, and the clinical characteristics, pathological features, treatment and prognosis were analyzed retrospectively. The cohort consisted of 17 participants, including 12 men and 5 women, with a mean age of 34.76 years. The most common locations of tumors were the bronchi and the lungs (9 cases, including 1 case involving the mediastinum), followed by the colon and bladder (2 cases each), and the omentum majus, mesocolon, stomach and peritoneal cavity (1 case each). Immunohistochemical staining demonstrated that the tumor cells exhibited positive staining for anaplastic lymphoma kinase p80 (13/17), smooth muscle actin (12/17), cytokeratin pan (6/17), vimentin (5/17) and desmin (4/17). The follow-up time was 18–114 months. A patient with epithelial inflammatory myofibroblast sarcoma (EIMS) succumbed to the disease, 1 case was lost to follow-up, 2 cases relapsed and the other 13 cases were considered cured. IMTs may be malignant or low-grade. EIMS is a rare and invasive variant of IMT. The clinical and imaging manifestations are often unique and vary among individuals. Once confirmed by pathology, radical surgery should be the first choice of treatment.     

Angiosarcoma of the breast after conservation therapy for invasive cancer, the incidence and outcome. An unforeseen sequela

Purpose. In the past 15 years breast conserving therapy (BCT) has become an important treatment option for primary breast cancer. Thirty three angiosarcomas (AS) after BCT have been described in a total of 20 published reports. Limited follow-up data and the lack of information on incidence of AS prompted the authors to review the comprehensive experience in the Netherlands. Methods. Between 1987 and 1995 twenty-one patients with BCT-associated AS were diagnosed in the Netherlands. Follow-up after diagnosis of AS ranged from 6 to 82 months with a median of 24 months. Information on the total number of patients treated with BCT and on the numbers of angiosarcoma in the breast was obtained. Results. The median interval between BCT and AS was 74 months (range: 29–106) and appeared to decrease with higher age. Detection of skin changes followed by incisional biopsy provided the diagnosis. Two year overall (OS) and disease free survivals were 72% (s.e. 10.9) and 35% (s.e. 10.7), respectively. Two year OS after initial complete surgical resection was 86% (s.e. 9.3) compared to 0% after incomplete resection of the AS (P=0.04). The estimated incidence of AS after BCT is 0.16%. Conclusions. BCT-associated AS arises after a relatively short interval. Although the incidence of AS is low, the absolute number of patients at risk is increasing. This calls for vigilance concerning skin changes occurring after BCT. An incisional biopsy provides the only reliable diagnosis. The prognosis appears to be related to the completeness of surgical resection.     

Continuing risk of ipsilateral breast relapse after breast-conserving therapy at long-term follow-up

PURPOSE: Currently, the local treatment of most patients with early invasive breast cancer consists of breast-conserving therapy (BCT). We have previously reported on the risk factors for ipsilateral breast relapse (IBR) in 1,026 patients treated with BCT after a median follow-up of 5.5 years. In the present study, we evaluated the IBR incidence and the risk factors for IBR after prolonged follow-up. METHODS AND MATERIALS: We updated the disease outcome for all 1,026 patients using the clinical information collected from the medical registration of The Netherlands Cancer Institute and performed step-wise proportional hazard Cox regression analysis to identify the risk factors associated with an increased risk of IBR after BCT at long-term follow-up. RESULTS: After a median follow-up of 13.3 years, 114 patients had developed an IBR as the first event. The IBR rate was 9.3% and 13.8%, respectively, at 10 and 15 years. Also, the increase in IBR was continuous without reaching a plateau, even after 15 years. Univariate analysis showed that involved surgical resection margins, young age, vascular invasion, and the presence and quantity of an in situ component are risk factors for IBR. Multivariate analysis showed that tumor-positive surgical resection margins (hazard ratio, 2.9; 95% confidence interval, 1.7-5.2, p = 0.0002) or the presence of vascular invasion (hazard ratio, 2.0; 95% confidence interval, 1.2-3.2, p = 0.004) is the major independent risk factor for IBR. CONCLUSIONS: The data from long-term follow-up showed a constant increase in IBR among patients treated by BCT, even after 15 years, without reaching a plateau. Involved surgical resection margins and vascular invasion were the most important risk factors for IBR.     

Ectopic Male Breast Cancer in Suprapubic Area That Relapsed with Hematogenous Metastasis

Tough ectopic male breast cancer is extremely rare, non-axillary ectopic male breast cancer is even rare. To date, the natural course and prognosis of this disease are not fully understood. Consequently, the appropriate treatment for this disease has not been established. We report on a patient with ectopic male breast cancer in the suprapubic area that relapsed with hematogenous metastasis 3 years after complete surgical resection and adjuvant treatment despite an early diagnosis. This unusual case highlights the need for new prognostic factors such as genomic profiling to predict whether ectopic male breast cancer is aggressive and to guide on the duration between follow-ups and the appropriate method for conducting them.     

Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumor (IMT) is a relatively rare soft tissue tumor. The reactive versus neoplastic pathogenesis of this tumor is unresolved. We found clonal chromosome aberrations involving 2p23 upon metaphase analysis of two IMTs. Fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 demonstrated rearrangement of the probe in both of these cases and in a third case, and immunohistochemistry revealed ALK expression in all three cases. 2p22-24 involvement has been reported previously in four additional cases of IMT. We suggest that chromosomal rearrangements involving 2p23 near or within ALK are recurrent alterations in IMT and that ALK may have a novel role outside its previously recognized realm of lymphoid neoplasms.     

Clinical and Histopathologic Correlates and Management Strategies for Inflammatory Myofibroblastic tumor of the lung. A case series and review of the literature

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm that may arise in soft tissues of nearly every organ. Although IMTs are the most common lung tumors in pediatric populations, these tumors are extremely rare in adults, constituting less than 1% of adult lung tumors. IMTs are characterized by proliferating spindle cells with variable inflammatory component. The biological behavior of lung IMTs in adults is highly unpredictable, which confounds diagnosis and treatment. We retrospectively investigated patients with pulmonary lesions and the histopathologic diagnosis of inflammatory myofibroblastic tumor or its synonymous names (Plasma Cell Granuloma, xanthogranuloma, inflammatory pseudotumor, fibroxanthoma, and fibrous histiocytoma) at the MD Anderson Cancer Institute in the period between August 2000 and August 2016. We describe 7 adult cases of IMT of the lung that were diagnosed at MD Anderson Cancer Center. These cases highlight the tumor’s variability in terms of clinical presentation, histopathology, and biologic behavior, and underscore the challenges in the management of these rare lung neoplasms.     

Management of non metastatic phyllodes tumors of the breast: review of the literature

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior.The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity.Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials.     

Inflammatory Myofibroblastic Tumor of the Urinary Bladder with Benign Pelvic Lymph Node Enlargement: A Case Report

Inflammatory myofibroblastic tumors (IMTs) rarely occur in the urinary bladder. It is apparently difficult to distinguish these tumors from other malignant spindle cell proliferations. Herein, we report a case of IMT of the urinary bladder with enlarged pelvic lymph nodes. The definitive pathological diagnosis could not be established by biopsy. Instead, the diagnosis of IMT of the urinary bladder was determined by a positive reaction to anaplastic lymphoma kinase by immunohistochemistry after radical cystectomy. No malignant findings were observed on histopathological evaluations of the enlarged lymph nodes.Key words: Inflammatory myofibroblastic tumor, Urinary bladder, Lymph node swelling     

A case of dermatofibrosarcoma protuberans in the skin over the breast

Dermatofibrosarcoma protuberans (DFSP) is a slow-growing but locally aggressive, fibrous tumor that has a high rate of local recurrence after surgical resection. This tumor occurs most commonly in the trunk and proximal extremities. In this report we present a case of dermatofibrosarcoma protuberans in the skin over the breast which was re-excised after pathological diagnosis, considering cosmetic aspects. Only three other cases of dermatofibrosarcoma protuberans of the anterior chest wall have been encountered in our hospital, and all of these cases were male. The presence of this tumor in the skin over the breast appears to be rare in females. Careful complete resection is recommended for this type of tumor.     

Inflammatory myofibroblastic tumors in childhood

BACKGROUND:

Inflammatory myofibroblastic tumors (IMTs) are myofibroblastic lesions with unpredictable biologic behavior that occur at a young age. For this report, the authors investigated clinicopathologic features in a series of pediatric IMTs. The objective of the study was to identify morphologic or immunohistochemical prognostic markers and the possible pathogenic role of human herpes virus 8 (HHV‐8).

METHODS:

Twenty‐six patients were observed over a period of 18 years. Clinical/histologic data were reviewed, and immunohistochemical/molecular studies were performed.

RESULTS:

Patients ages 8?216 months (median age, 60 months) presented with tumors of the lung‐bronchus (8 patients), abdomen (17 patients), and thoracic wall (1 patient). Twenty‐one patients underwent complete excision, and microscopic or macroscopic residual disease was present in 5 of those patients. Chemotherapy was received by 5 patients. After a median follow‐up of 6.6 years, 24 patients were in complete remission, and 2 patients had died of disease. Local recurrences were observed in 6 patients (including 4 recurrences that occurred after a complete excision). Cytologic atypia, low inflammatory infiltrate, and a rich myxoid pattern were detected in patients who had recurrent disease or a poor prognosis. Anaplastic lymphoma kinase (ALK) was positive in 7 patients (including 2 patients with recurrent disease). No correlation between clusterin expression and prognosis was demonstrated. HHV‐8 was identified in 1 pulmonary IMT.

CONCLUSIONS:

IMTs are locally aggressive lesions. In this series, the local recurrence rate was 23%, and the 5‐year and 10‐year event‐free survival rates were 87.4% and 72.8%, respectively. The results indicated that the treatment of choice is a complete, nonmutilating excision; chemotherapy may be given to patients who have microscopic or macroscopic residual disease, although the results are controversial; cytologic atypia and positive ALK status are more frequent in aggressive tumors, whereas metastatic tumors are negative for ALK; and HHV8 is not involved in the pathogenesis of IMT. Cancer 2010. © 2010 American Cancer Society.     

Thermal Ablation as an Alternative for Surgical Resection of Small (≤ 2 cm) Breast Cancers: A Meta-Analysis

Women with early-stage breast cancer have an excellent prognosis with current therapy, but could presumably be treated less invasively, without the need for surgery. The primary goal of this meta-analysis was to examine whether thermal ablation is an effective method to treat early-stage breast cancer.Studies reporting on complete ablation rate after thermal ablation as a treatment of small breast cancers (≤ 2 cm) were included. Methodologic quality of included studies was assessed using MINORS criteria. Complete ablation rates are given as proportions, and meta-regression and subgroup analyses were performed.The overall complete ablation rate in 1266 patients was 86% and was highest after radiofrequency ablation (RFA) (92%). Local recurrence rates varied from 0% to 3%, with a median follow-up of 15 to 61 months. Overall, complication rates were low (5%-18% across techniques) and were highest after high-intensity focused ultrasound ablation and lowest after cryoablation. Cosmetic outcome was good to excellent in at least 85% of patients but was reported infrequently and long-term results of cosmetic outcome after thermal ablation and radiotherapy are still lacking.Thermal ablation techniques treating early-stage breast cancer (≤ 2 cm) are safe and effective based on complete ablation rate and short-term local recurrence rates. Especially, RFA, microwave ablation, and cryoablation are promising techniques as an alternative to surgical resection without jeopardizing current treatment effectiveness or safety. Owing to great heterogeneity in the included studies, a formal recommendation on the best technique is not possible. These findings warrant the design of large randomized controlled trials comparing thermal ablation and breast-conserving surgery in the treatment of T1 breast cancer.     

Successful multimodal treatment of a breast cancer patient with a recurrence invading the chest wall

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.