Abstract
Purpose
The study objective is to evaluate the clinical features and outcomes of patients treated for head and neck malignant fibrous histiocytoma at a tertiary care medical facility.
Materials and methods
This is a retrospective case series of 17 adult subjects with malignant fibrous histiocytoma of the head and neck who were treated between January 1, 1965, and December 31, 2010. This study was conducted using patient charts at a tertiary medical center. Subject selection was conducted using Current Procedural Terminology numbers; International Classification of Diseases, Ninth Revision, codes; and a search of the tumor registry.
Results
Chart review of the 17 identified subjects revealed an overwhelming male predominance (88%) with an overall mean age of 69 years(52–87 years). Thirteen patients (78%) underwent some form of surgical resection, 6 patients (35%) received radiation therapy, and 6 (35%) were given chemotherapy over the course of treatment. Nine tumors (53%) had a cutaneous origin, whereas 8 lesions (47.1%) were found in the soft tissue of the head and neck region. The local recurrence rate following a single resection was 46%. Overall median survival following diagnosis was found to be 65 months, with a 5-year survival rate of 52%. Median disease-free survival was 20 months, with a 5-year disease-free survival rate of 37%. Overall median and 5-year survival rates were found to increase with clear surgical margins, as was 5-year survival.
Conclusions
Aggressive surgical management to achieve clear margins is central to the effective treatment of malignant fibrous histiocytoma of the head and neck. Metastatic disease portends a dismal prognosis.
1
Introduction
Malignant fibrous histiocytoma (MFH) is a soft tissue sarcoma first identified in 1963 by Ozzello et al and described in detail by O’Brien and Stout in 1964. Although the debate over its exact histogenesis continues, this tumor is typically characterized as a pleomorphic sarcoma with both fibroblastic and histiocytic differentiation in varying proportions . The nomenclature of this tumor has varied historically, and it has also been referred to as malignant fibrous xanthoma or confused with similar skin entities such as dermatofibrosarcoma protuberans and atypical fibroxanthoma . Although previously considered a diagnosis of exclusion, contemporary advances in the understanding of sarcoma pathology have resulted in better differentiation of tumors once classified as MFH into new subsets. This reclassification has resulted in a sharp decline in the incidence of MFH . As a result, some authors now advocate a shift in nomenclature from MFH to pleomorphic undifferentiated sarcoma ( PUS ) .
Under the 2002 World Health Organization guidelines , MFH is considered a rare tumor. As currently classified, this tumor comprises no more than 5% of all soft tissue sarcomas diagnosed in adults . Malignant fibrous histiocytoma affects the lower extremities, the upper extremities, and the retroperitoneum in order of decreasing incidence . Less than 10% of MFHs originate in the head and neck, but it remains one of the most common sarcomas of this region. It accounts for less than 0.5% of all head and neck malignancies .
Malignant fibrous histiocytoma often presents as a painless, enlarging mass of less than 6 months’ duration . Any specific symptoms are often related to the exact location of the tumor and its proximity to adjacent structures. Accepted treatment is complete excision of the primary tumor with wide surgical margins . Regional metastases are uncommon, making neck dissection unnecessary in the vast majority of cases . Adjuvant radiotherapy is used in cases where either the tumor is unresectable or clear surgical margins are not achieved .
Because of the rare nature of MFH, a deficit exists in literature regarding this tumor. Randomized clinical trials are a virtual impossibility with such low incidence. Retrospective case series are one of the few tools available for review of effective treatment strategies and patient outcomes. This clinical information will hopefully augment the growing base of information about this disease and better allow physicians to effectively counsel and treat patients diagnosed with this condition.
2
Methods
2.1
Human subjects protection
This study was approved by the Institutional Review Board of the Wake Forest School of Medicine. To help ensure subject privacy and confidentiality, only a unique study identifier appeared on the data collection form. All collected patient identifying information corresponding to the unique study identifier was maintained on a separate master log. The master log was kept secure with access limited to designated study personnel.
The data were stored in a password-protected computer file with access only allowed to members of the research team. Data collection took place over a period of 2 months and will be destroyed within 5 years. Following publication, subject identifying information will be destroyed at the earliest opportunity.
2.2
Design
This study was a retrospective case series chart review of men and women, 18 years and older, with MFH of the head and neck. Following full approval by the Institutional Review Board, charts were identified for review by conducting a search of patients with Current Procedural Terminology and International Classification of Diseases, Ninth Revision, codes treated for head and neck MFH at Wake Forest University Baptist Medical Center from January 1, 1965, to December 31, 2010.
2.3
Subject selection
Patients treated but without follow-up data were excluded. Patients younger than 18 years were also excluded.
A preliminary inquiry of the tumor registry was performed by the Translational Science Institute and Wake Forest Division of Public Health Sciences. Subjects who appeared to be diagnosed with MFH or with diagnoses similar to this condition were identified. The principal International Classification of Diseases, Ninth Revision, code was 171.0, which encompasses most soft tissue sarcomas of the head and neck. The paper and electronic medical records of these subjects were reviewed for definitive diagnosis, clinical measures, and outcome measures.
2.4
Clinical measures
Clinical measures included demographic information such as sex, date of birth, date of death, tumor location, presenting signs and symptoms, surgical margins, follow-up imaging, radiation targets and duration (if applicable), and chemotherapy drugs and duration (if applicable). Tumor grade, when available, was also recorded. Tumors classified as “pleomorphic” were categorized as high grade, tumors with “storiform” features were classified as intermediate grade, and those with “myxoid” features were listed as low grade.
2.5
Outcome measures
Outcome measures included symptom control (based on presenting symptoms and new symptoms that developed during treatment), treatment failure (based on presence of active disease at the conclusion of therapy), change in tumor size, and the presence of other complications. Median survival was calculated using the date of last treatment along with the patient’s date of death or, if that was unavailable, the clinic appointment at which the patient was last seen alive. Date of death was obtained from the medical records and/or search of public records and obituaries.
2.6
Statistical analyses
Results were analyzed initially using descriptive statistics. Means, medians, and ranges were calculated initially. Comparisons between groups were done using χ 2 tests for proportions, and t tests or analysis of variance procedures for continuous variables. Regression analysis was performed to identify independent outcome predictors. Other inferential statistical analyses were conducted as appropriate.
2
Methods
2.1
Human subjects protection
This study was approved by the Institutional Review Board of the Wake Forest School of Medicine. To help ensure subject privacy and confidentiality, only a unique study identifier appeared on the data collection form. All collected patient identifying information corresponding to the unique study identifier was maintained on a separate master log. The master log was kept secure with access limited to designated study personnel.
The data were stored in a password-protected computer file with access only allowed to members of the research team. Data collection took place over a period of 2 months and will be destroyed within 5 years. Following publication, subject identifying information will be destroyed at the earliest opportunity.
2.2
Design
This study was a retrospective case series chart review of men and women, 18 years and older, with MFH of the head and neck. Following full approval by the Institutional Review Board, charts were identified for review by conducting a search of patients with Current Procedural Terminology and International Classification of Diseases, Ninth Revision, codes treated for head and neck MFH at Wake Forest University Baptist Medical Center from January 1, 1965, to December 31, 2010.
2.3
Subject selection
Patients treated but without follow-up data were excluded. Patients younger than 18 years were also excluded.
A preliminary inquiry of the tumor registry was performed by the Translational Science Institute and Wake Forest Division of Public Health Sciences. Subjects who appeared to be diagnosed with MFH or with diagnoses similar to this condition were identified. The principal International Classification of Diseases, Ninth Revision, code was 171.0, which encompasses most soft tissue sarcomas of the head and neck. The paper and electronic medical records of these subjects were reviewed for definitive diagnosis, clinical measures, and outcome measures.
2.4
Clinical measures
Clinical measures included demographic information such as sex, date of birth, date of death, tumor location, presenting signs and symptoms, surgical margins, follow-up imaging, radiation targets and duration (if applicable), and chemotherapy drugs and duration (if applicable). Tumor grade, when available, was also recorded. Tumors classified as “pleomorphic” were categorized as high grade, tumors with “storiform” features were classified as intermediate grade, and those with “myxoid” features were listed as low grade.
2.5
Outcome measures
Outcome measures included symptom control (based on presenting symptoms and new symptoms that developed during treatment), treatment failure (based on presence of active disease at the conclusion of therapy), change in tumor size, and the presence of other complications. Median survival was calculated using the date of last treatment along with the patient’s date of death or, if that was unavailable, the clinic appointment at which the patient was last seen alive. Date of death was obtained from the medical records and/or search of public records and obituaries.
2.6
Statistical analyses
Results were analyzed initially using descriptive statistics. Means, medians, and ranges were calculated initially. Comparisons between groups were done using χ 2 tests for proportions, and t tests or analysis of variance procedures for continuous variables. Regression analysis was performed to identify independent outcome predictors. Other inferential statistical analyses were conducted as appropriate.
3
Results
A total of 1519 patients were identified with a possible diagnosis of MFH. Further investigation revealed a total of 26 patients with a true diagnosis of head and neck MFH, excluding histologically similar but distinct diagnoses. Following data collection, 9 subjects were excluded because of age, improper classification in the tumor registry, or lack of adequate follow-up documentation. This final screening left a total of 17 patients suitable for inclusion in this series.
In this particular study, an overwhelming majority of the subjects were male (88%). The majority of subjects presented with a solitary, painless, enlarging mass that had often grown over a period of months before the patient sought medical care. This was often the only symptom at the time of diagnosis, although a distinct minority of patients reported dysphagia, hoarseness, and/or cough at presentation. Of the 17 patients included in this study, a small majority had primaries of the skin vs soft tissue of the head and neck ( Table 1 ). Three patients (17.6%) had metastatic disease at presentation; and 5 patients (29.4%) developed new metastases despite treatment, including all 3 patients who had initially presented with metastases. Of the 10 patients who achieved local control, 2 (20%) went on to develop distant metastases. The lungs were the most common site of metastasis, followed by brain, nerve, lymph nodes, and bone.
