Fritchie, Karen J

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan–Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by “low risk” and “moderate/intermediate and high risk” tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features. The vast majority of dedifferentiated liposarcomas show MDM2 amplification, whereas limited data exists as to the MDM2 status of MFS. We sought to explore the rate of MDM2 amplification in cases of classic MFS. Our archives were searched for MFS; only subcutaneous well-sampled resections were included. FISH for MDM2 amplification was performed on each tumor. A cohort of myxoid dedifferentiated liposarcoma resections was studied for comparison. Twenty-two MFS arose in patients aged 44 to 85 years. All tumors contained an infiltrative population of atypical cells embedded in a myxoid stroma with curvilinear blood vessels. MDM2 amplification by FISH was identified in 3 (of 22; 14%) tumors. Available follow up on 17 patients (range 1-96 months; median 13 months) revealed 6 patients with local recurrence and 1 with distant metastasis. Of 3 patients with MDM2- amplified MFS, 1 experienced recurrence and died of unrelated causes, while the second was alive without disease 12 months after diagnosis. Even though the rate of MDM2 amplification by FISH in MFS appears to be low, a subset of cases may show this genetic alteration, which pathologists should be aware of to avoid misclassification as myxoid dedifferentiated liposarcomas. Further studies are necessary to determine if amplification status adds prognostic value.

Aims . Fibrous dysplasia (FD) is a benign fibro-osseous neoplasm that most commonly arises in the ribs, femur, and craniofacial bones. We analyzed features of FD arising in the spine/short tubular/small bones of the hands/feet (STSBHF), specifically assessing for pattern of bone formation (conventional, complex/anastomosing, psammomatoid/cementum like), myxoid change, and presence of osteoclast-type giant cells. Materials and methods . A total of 1958 cases of FD were reviewed, of which 131 arose in the spine/STSBHF representing 2.5% of institutional and 10% of consultation cases, respectively. Eighty-six cases had material available for review. Anatomic sites included vertebrae ( n = 58, 67%), short tubular bones ( n = 20, 23%), and small bones of the hands/feet ( n = 8, 9%). The most common morphologic pattern of bone identified was conventional ( n = 77, 90%), followed by complex/anastomosing ( n = 22, 26%) and psammomatoid/cementum like ( n = 22, 26%). Eighteen cases (21%) had matrix-poor areas. Hypercellular areas were identified in 6 cases, 2 cases of which showed matrix-poor areas. Osteoclast-type giant cells were noted in 9 cases and myxoid change was present in 3 cases. Radiologic imaging studies available for 41 cases nearly all demonstrated features typical of FD, but the diagnosis was not predicted due to the unexpected location. Conclusions . FD arising in the spine/STSBHF is rare and frequently results in expert consultation. A significant number of cases exhibited less commonly recognized patterns of bone formation, and stromal changes including osteoclast-type giant cells, and matrix poor areas. Furthermore, imaging features in the STSBHF are often less specific. Awareness of the morphologic spectrum at these locations coupled with radiologic correlation should aid in accurate classification.

Objective. We explore the clinicopathologic features of Ewing sarcoma (ES) presenting in older adulthood. Methods. Cases of molecularly confirmed ES arising in patients aged ≥40 years were evaluated. Results. Fifty patients were identified (33 males/17 females; 41-86 years). The majority of tumors (41) arose at extraskeletal sites, while 9 were bone primaries. Twenty-eight cases showed nested architecture, while the remaining cases showed sheet-like growth. Tumor cytology was categorized as conventional (n = 39), crushed (n = 5), clear cell (n = 4), rhabdoid (n = 3), and epithelioid (n = 2). Fifty percent had necrosis, while rosettes were noted in 1 case. Immunostains performed ranged from 1 to 28 (median = 10). Follow-up (n = 43, 1-147 months) revealed 15 patients with metastasis. Conclusion. Although rare, ES should be considered in the differential diagnosis for round cell malignancies in older adult patients. In this cohort, ES is most often extraskeletal, and may show unusual morphologic features, closely simulating more common neoplasms in this age group.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and spindle cell lipoma are lipomatous tumors with distinct clinical, molecular, and prognostic features. Although histological and immunophenotypic features can overlap between ALT/WDL and spindle cell lipoma, the oncogenesis and clinical behavior are markedly different. In borderline cases, molecular analysis for MDM2 or CDK4 amplification can aid in distinguishing ALT/WDL from spindle cell lipoma. Although dedifferentiated liposarcoma has been reported to harbor both MDM2 amplification and loss of the RB1 region, we are not aware of a reported RB1 loss in well-differentiated ALT/WDL. In this article, we present a 69-year-old woman with a lipomatous tumor in the gluteal region that histologically, immunohistochemically, and molecularly mimicked spindle cell lipoma (with positive immunohistochemical staining for CD34 and loss of the RB1 gene region), yet harbored amplification of MDM2 and CDK4 confirmed by fluorescence in situ hybridization, supporting classification as ALT/WDL. This case strengthens the argument that in atypical clinical contexts, molecular studies for MDM2/CDK4 should be considered in tumors resembling spindle cell lipoma.

Aims Limited data exist on atypical lipomatous tumour (ALT)/well‐differentiated liposarcoma (WDL) and de‐differentiated liposarcoma (DDLPS) in children and young adults. Methods and results Cases of ALT/WDL/DDLPS arising in patients aged ≤ 40 years were collected from multiple institutional and consultation archives. A total of 116 cases of ALT/WDL (75) and DDLPS (41) were identified, representing fewer than 5% of these tumours seen at our institutions during this time‐period. The patients (59 male/57 female) ranged in age from 8 to 40 years. Sites included deep central (abdomen/retroperitoneum/pelvis/groin) ( n = 60), extremity ( n = 42), trunk ( n = 5), head/neck ( n = 8) and mediastinum ( n = 1). De‐differentiated patterns included: high‐grade pleomorphic sarcoma, myxofibrosarcoma‐like, heterologous rhabdomyoblastic differentiation, low‐grade spindle cell sarcoma and homologous lipoblastic differentiation. Forty‐one patients experienced a local recurrence and 11 patients with DDLPS developed metastasis. ALT arising in the extremities had lower recurrence rates than deep central WDL (5‐year recurrence‐free survival 88.9% versus 59.0%; P = 0.002), while patients with deep central DDLPS experienced significantly more adverse events compared to WDL at this site (5‐year event‐free survival 11.9% versus 59.0%) ( P < 0.0001). Seven (of eight) head/neck tumours had follow‐up available; five recurred, and one patient (DDLPS) with recurrence also experienced a metastasis. The single mediastinal tumour (DDLPS) recurred and metastasised. Conclusion ALT/WDL and DDLPS occurring in patients aged ≤ 40 years is rare, but exhibits similar morphological features to its counterparts in older adults, including potential for heterologous and homologous de‐differentiation in the latter. Although case numbers are limited, tumours arising in the head and neck exhibit high rates of adverse events, suggesting that classification as WDL rather than ALT is more appropriate.

AimsChondroblastomas (CB) are rare bone tumours that typically arise in the epiphysis/apophysis of long bones in skeletally immature patients. We explore the clinicopathological features of CB presenting in adults.Methods and resultsCB in patients ≥20 years of age were retrieved from our institutional archives. Thirty‐nine CB were identified (29 male/10 female; aged 20–54 years). Twenty (51%) cases occurred in long tubular bones, 10 (26%) in small bones of the feet, five (13%) in flat bones and four (10%) in the patella. All cases showed classic cytological features of CB, and chondroid matrix was universally present. Calcification was identified in 10 cases (26%), including various combinations of serpiginous (n = 7), punctate (n = 6), classic chicken‐wire (n = 4) and psammomatous (n = 2) patterns. Haemosiderin (n = 19), woven bone (n = 13), secondary aneurysmal bone cyst formation (n = 8), foamy macrophages (n = 4), hyalinised vascular spaces (n = 2) and cholesterol clefts (n = 2) were noted. Follow‐up information (n = 32, 1–452 months) revealed local recurrence in three patients, all >40 years of age with flat bone origin, one of which developed pulmonary metastases 132 months after initial diagnosis.ConclusionsCB in patients >20 years of age more frequently involves the short bones of the hands/feet and flat bones compared to those arising in their younger counterparts. A subset may harbour extensive serpiginous or psammomatous calcification rather than the classic chicken‐wire pattern. Although the overall local recurrence rate in adulthood is approximately 10%, all three patients with recurrent disease had tumours involving flat bones, suggesting that tumours arising in these sites may behave more aggressively.