Jeanne M. Meis

Inflammatory fibrosarcoma of the mesentery and retroperitoneum: A tumor closely simulating inflammatory pseudotumor

We report 38 cases of inflammatory fibrosarcoma occurring in 23 females and 15 males, 2 months to 74 years of age (median, 8.5 years; mean, 15 years) with symptoms of abdominal pain (17 cases), anemia (21 cases), fever (14 cases), mass (16 cases), and gastrointestinal obstruction (7 cases). Primary tumor sites included mesentery and retroperitoneum (31 cases), omentum (two cases), mediastinum (two cases), liver (one case), diaphragm (one case), and abdominal wall (one case). Sizes ranged from 2.4 cm to 20 cm (mean, 9.6 cm). Follow-up data in 27 cases revealed local recurrences in 10 patients, with multiple local recurrences in three and histologically proven distant metastases to lung (two cases) and brain (one case). Five patients died from their disease (median, 20 months). All tumors, including metastases, consisted of fibroblasts, myofibroblasts, and plasma cells, with variable degrees of fibrosis and calcification. Immunostains indicate myofibroblastic differentiation; 18 of 20 (90%) stained for actin, 15 of 18 (83%) for vimentin, and 10 of 13 (77%) for keratin (primarily in a submesothelial location). Ultrastructural studies also disclosed myofibroblastic features. The locally aggressive, recurrent nature of these neoplasms, as well as the occurrence of metastases and tumor deaths, indicate that they are potentially malignant neoplasms that we believe are better classified as inflammatory fibrosarcomas, not as cellular inflammatory pseudotumors.

Malignant peripheral nerve sheath tumors (malignant schwannomas) in children

&NA; We studied the clinical and pathologic features of 78 malignant peripheral nerve sheath tumors in children ≤ 15 years of age. There were 42 boys and 36 girls, with a median age of 10 years. The majority of the tumors (42, or 54%) were central or axial in location; the rest were peripheral. Sixteen patients (21%) had a history of von Recklinghausens disease. Fourteen (18%) had a malignant peripheral nerve sheath tumor arising in a nerve trunk or a neurofibroma and were unassociated with von Recklinghausens disease. Patients typically presented with a painful mass of variable duration. Tumors ranged from 2 to 33 cm (median, 7.5 cm) and demonstrated a wide histologic spectrum that included spindled, epithelioid, and primitive neuroepithelial‐like cells as well as heterologous elements (11). Immunohistochemical staining revealed S‐100 protein in 28 of 50 cases (56%) as well as vimentin (13 of 21 cases, or 62%), Leu 7 (22 of 49 cases, or 45%), actin (eight of 20 cases, or 40%), and keratin (seven of 27 cases, or 26%). Survival status was known for 57 patients (73%). Kaplan‐Meier estimates revealed a median survival of 45 months. Half of the patients had local recurrences at 12 months, and half had metastases at 24 months, most commonly to lungs, followed by lymph nodes, liver, bone, soft tissue, and brain. Age ≥ 7 years, male sex, presence of von Recklinghausens disease, central location, larger tumor size, and tumors with ≥ 25% necrosis were found to be potentially significant adverse prognostic indicators by univariate analysis. Multivariate analysis revealed that larger tumor size, age ≥ 7 years, tumor necrosis ≥ 25%, and von Recklinghausens disease to be independent adverse prognostic factors.

Radiation-induced sarcomas of the chest wall†

Sixteen patients are presented who had sarcomas of the chest wall at a site where a prior malignancy had been irradiated. The first malignancies included breast cancer (ten cases), Hodgkins disease (four cases), and others (two cases). Radiation doses varied from 4200 to 5500 R (mean, 4900 R). The latency period ranged from 5 to 28 years (mean, 13 years). The histologic types of the radiation‐induced sarcomas were as follows: malignant fibrous histiocytoma, nine cases; osteosarcoma, six cases; and malignant mesenchymoma, one case. The only long‐term survivor is alive and well 12 years after resection of a clavicular chondroblastic osteosarcoma. Three cases were recently diagnosed. Despite aggressive multimodality treatment, the remaining 13 patients have all died from their sarcomas (mean survival, 13.5 months). All patients have apparently been cured of their first malignancies. Chemotherapy was ineffective. No treatment, including forequarter amputation, appeared to palliate the patients with supraclavicular soft tissue sarcomas. Major chest wall resection offered good palliation for seven of eight patients with sarcomas arising in the sternum or lateral chest wall. Close follow‐up is needed to detect signs of these sarcomas in the ever‐increasing number of patients receiving therapeutic irradiation.

Chondroid lipoma: A unique tumor simulating liposarcoma and myxoid chondrosarcoma

We report 20 cases of a peculiar fatty tumor that occurred in 16 female and four male patients who were 14-70 years old (median, 36 years). Most lesions were situated in the subcutis, superficial muscular fascia, or skeletal muscle of the limbs and limb girdles (15), trunk (3), and the head and neck (2). They were 1.5-11 cm in size (median, 4 cm) and usually described as yellow (13 of 15) and encapsulated (13 of 15). Microscopically they were well circumscribed and consisted of nests, strands, and sheets of eosinophilic and vacuolated cells, which contained glycogen and fat droplets, resembling brown fat cells, lipoblasts and chondroblasts. In all cases there was a variable background of mature adipose tissue associated with a prominent, partially fibrinous to hyalinized myxoid matrix that contained acid mucopolysaccharides usually resistant to hyaluronidase digestion. Several cases had foci of serous atrophy, perivascular fibrosis, and small thrombi; two were focally calcified. The lesions stained for S100 protein (11 of 12), vimentin (10 of 11), and CD68 antigen with KP1 (9 of 11); focal staining for keratin was also seen (4 of 11), but none stained for epithelial membrane antigen or actin or with HMB45. Follow-up in 12 cases (median, 9.5 years) revealed no local recurrences or metastases. Despite its deep location and atypical cellular features, the lesions nonaggressive behavior suggests it is benign and neither a myxoid liposarcoma nor a myxoid chondrosarcoma, with which it is most frequently confused. The presence of glycogen in vacuolated fat cells is similar to brown fat, and the presence of sulfated stromal mucins supports focal chondroid differentiation. Although the pathogenesis remains uncertain, a lipoma with hibernomatous features, myxoid change, chondroid metaplasia, and secondary degenerative features is favored over a lipogranulomatous process.

Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions

Myxoinflammatory fibroblastic sarcoma (MIFS) is a low‐grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array‐based comparative genomic hybridization, global gene expression, and real‐time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up‐regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11–12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH. Copyright

Myolipoma of soft tissue

Nine cases of a previously undescribed benign soft tissue tumor are reported. They were composed of variable amounts of benign smooth muscle and mature adipose tissue. Patient ages ranged from 28 to 73 years. One was located in the subcutaneous adipose tissue, one in the rectus sheath of the anterior abdominal wall, two within the abdominal cavity and attached to the abdominal wall, two in the inguinal region, and three in the retroperitoneum. Sizes varied between 3.5 and 26 cm and averaged 16 cm in greatest dimension. Two of the retroperitoneal tumors were incidental findings during other operative procedures. The remaining seven cases were clinically palpable masses. Eight of the nine lesions were originally diagnosed as benign, and another (retroperitoneal) was diagnosed as well-differentiated liposarcoma. Five of the tumors were at least partially encapsulated. In three of the cases, a nonlipomatous component was grossly recognized. Although the benign nature of this lesion is usually recognized in superficial locations, deeply situated tumors are more likely to be confused with a well-differentiated liposarcoma.

Proliferative fasciitis and myositis of childhood

Eleven cases of proliferative fasciitis and myositis in children, ages 2.5 months to 13 years, are presented. Eight lesions averaging 2.3 cm in size occurred in the extremities, two in the head and neck region and one on the chest wall. Like proliferative fasciitis and myositis in adults, these lesions consisted of admixtures of large polygonal to spindled, ganglion-cell-like fibroblasts with vesicular nuclei and prominent inclusion-like nucleoli. Seven of 11 lesions were initially diagnosed as sarcomas, most commonly rhabdomyosarcoma. Four patients were treated by wide excision (three with regional lymphadenectomy), three received chemotherapy, and one was given radiation therapy. There were some histologic differences from adult-type proliferative fasciitis and myositis. The childhood lesions were generally well circumscribed, lobulated, extremely cellular with less collagen production, and often associated with acute inflammation and microscopic foci of necrosis. Immunohistochemical comparison with adult proliferative fasciitis and myositis showed similar immuneprofiles; the ganglion-like cells stained for vimentin and actin and focally with KP1, suggesting myofibroblastic and histiocytic features. None of the lesions stained for keratin, desmin, or S-100 protein. Ultrastructural examination of two cases revealed cells with a constellation of fibroblastic, myofibroblastic, and histiocytic features. Follow-up of seven patients, averaging 58 months from diagnosis, confirmed that all are alive and well. Recognition of this cellular variant of proliferative fasciitis and myositis is important to prevent misdiagnosis as a sarcoma and unnecessary, excessive therapy.

FUS rearrangements are rare in 'pure' sclerosing epithelioid fibrosarcoma

Several recent reports have described low-grade fibromyxoid sarcoma with sclerosing epithelioid fibrosarcoma-like areas. We evaluated cases of pure sclerosing epithelioid fibrosarcoma lacking areas of low-grade fibromyxoid sarcoma for FUS rearrangement to determine whether this entity could be related to low-grade fibromyxoid sarcoma. Available formalin-fixed paraffin-embedded tissue of 27 sclerosing epithelioid fibrosarcoma from 25 patients was retrieved and tabulated with clinical information. Unstained slides from formalin-fixed paraffin-embedded blocks were prepared and fluorescence in-situ hybridization was performed using a commercial FUS break-apart probe. The median patient age at presentation was 50 (range, 14–78) years, with 14 males and 10 females. Sclerosing epithelioid fibrosarcoma most commonly involved the extremities (n=8) or chest (n=6). Sixteen patients had a median follow-up of 17 (range, 1–99) months; seven were alive and well at 12 (range, 5–30) months; three alive with disease at 28 (range, 9–99) months; five dead of disease at a median of 22 (range, 1–36) months and one was dead of unknown causes. Twelve patients were known to have metastases; the most common site was lung (n=7), followed by bone (n=3), lymph nodes (n=2) and peritoneum (n=1). Only 2 of 22 (9%) analyzable cases of sclerosing epithelioid fibrosarcoma showed rearrangement in the FUS locus by fluorescence in-situ hybridization. Although cytogenetically confirmed low-grade fibromyxoid sarcoma can have sclerosing epithelioid fibrosarcoma-like areas, FUS rearrangement, which is characteristic of low-grade fibromyxoid sarcoma, appears to be relatively rare in pure sclerosing epithelioid fibrosarcoma.

Hodgkin's disease involving the breast and chest wall

Eighteen patients with Hodgkins disease involving the breast or chest wall were identified from the M. D. Anderson Hospital and Tumor Institute pathology files from 1962 through 1984. All of these cases were nodular sclerosing Hodgkins disease. Nine of the 18 patients had Hodgkins disease involving the breast or chest wall at initial presentation. The remaining nine cases represented recurrences involving the breast or chest wall. Breast or chest wall involvement represented extranodal extension and/or involvement of another supradiaphragmatic lymph node group. No marked difference in survival was found between the initial and recurrent groups. Those patients with breast involvement had a better prognosis than those with chest wall involvement. Hodgkins disease involving the breast or chest wall as an initial presentation or a recurrence does not necessarily indicate an accelerated phase of the disease. Breast or chest wall involvement is probably due to Hodgkins disease involving the intramammary or internal mammary lymph nodes, or is due to direct mediastinal extension into the chest wall.

Osseous myxochondroid sarcoma: A detailed study of 5 cases of extraskeletal myxoid chondrosarcoma of the bone

Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm with a characteristic translocation usually involving NR4A3 and EWSR1. EMC has rarely been reported in the bone and may be confused with conventional chondrosarcoma with myxoid features or various small round cell sarcomas. We present 5 cases of molecularly confirmed EMC arising primarily in the bone. Patients included 4 men and 1 woman, aged 38 to 77 years (median 54 y). Tumors arose in the ilium (2 cases), manubrium, rib, and humerus. Four tumors extensively infiltrated and destroyed preexisting bone with cortical breakthrough and associated soft tissue extension; 1 case demonstrated only focal cortical breakthrough. Microscopically, 2 cases had small round cell features; 1 of these was hypercellular, whereas the other was hypocellular with abundant myxochondroid matrix. Three cases were composed of eosinophilic spindled cells with variable fascicular to corded or wreath-like growth patterns. Fluorescence in situ hybridization was positive for both EWSR1 and NR4A3 translocation in 3 cases; rearrangement for EWSR1 or NR4A3, but not both, was seen in 2 tumors. After definitive therapy, 1 patient experienced multiple local recurrences at 36 months and died of disease at 61 months. Two patients developed lung metastases at 26 and 74 months and are alive with disease at 44 and 74 months, respectively. Two patients are disease free at 5 and 24 months. EMC of the bone is a diagnostic dilemma and requires molecular confirmation. We propose to classify tumors with the appropriate phenotype and molecularly confirmed NR4A3/EWSR1 rearrangements as myxochondroid sarcoma, either osseous or extraskeletal variants.