ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

AIMS: The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). METHODS AND RESULTS: We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). CONCLUSION: We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age.

Myoepithelial tumors of the soft tissue and bone occurring in patients 21 years of age and younger are rare, and their clinicopathologic features remain incompletely understood. We studied a well-characterized series of 40 such tumors. Cases were retrieved from our archives for the period 2009-2022 and re-reviewed. Available immunohistochemical and molecular genetic data was collected. Clinical information including available follow-up was obtained. The tumors occurred in 18 males and 22 females, ranging from 3 months to 21 years of age (median 11.5 years), and involved a wide variety of soft tissue (n = 36) and bone (n = 4) locations. Histologically benign myoepithelial tumors tended to occur in adolescents (median age 14.5 years; range 5-21 years), whereas myoepithelial carcinomas occurred in younger patients (median age 8.5 years; range 3 months-20 years). Microscopically, the tumors showed a complex admixture of epithelioid, plasmacytoid and spindled cells in a variably hyalinized, myxoid, chondroid or chondromyxoid background. Small subsets of histologically malignant tumors had rhabdoid or "round cell" features. Immunohistochemistry showed 35/40 (88%) cases to be positive with at least one keratin antibody. The 5 keratin-negative tumors were uniformly positive for S100 protein and/or SOX10 and expressed EMA (4 cases) and/or p63 (3 cases). EMA, SMA and GFAP were positive in 21/25 (84%), 13/21 (62%), and 8/21 (38%) tumors, respectively. SMARCB1 and SMARCA4 expression was retained in 29/31 (94%) and 22/22 (100%) of cases, respectively. FISH for EWSR1 gene rearrangement was positive in 6/18 (33%) tested cases. Two EWSR1-negative tumors were also FUS-negative. NGS identified EWSR1::POU5F1, FUS::KLF17, and BRD4::CITED1 gene fusions in 3 tested cases. Clinical follow-up (22 patients; median 23 months; range 1-119 months) showed 3 patients with local recurrences and 5 with distant metastases (lymph nodes, lung, and brain). Three patients died of disease, 3 were alive with recurrent or unresectable disease, and 16 were disease-free. Adverse clinical outcomes were seen only in patients with malignant tumors. We conclude that myoepithelial neoplasms of soft tissue and bone are over-repesented in patients ≤21 years of age, more often histologically malignant, and potentially lethal. Histologic evaluation appears to reliably predict the behavior of these rare tumors.

Novel CRTC1::MRTFB(MKL2) Gene Fusion Detected in Myxoid Mesenchymal Neoplasms With Myogenic Differentiation Involving Bone and Soft Tissues.

Appropriate classification of fusion-driven bone and soft tissue neoplasms continues to evolve, often relying on the careful integration of morphologic findings with immunohistochemical, molecular, and clinical data. Herein, we present 3 cases of a morphologically distinct myxoid mesenchymal neoplasm with myogenic differentiation and novel CRTC1::MRTFB (formerly MKL2) gene fusion. Three tumors occurred in 1 male and 2 female patients with a median age of 72 years (range: 28-78). Tumors involved the left iliac bone, the right thigh, and the left perianal region with a median size of 4.0 cm (4.0-7.6 cm). Although 1 tumor presented as an incidental finding, the other 2 tumors were noted, given their persistent growth. At the time of the last follow-up, 1 patient was alive with unresected disease at 6 months, 1 patient was alive without evidence of disease at 12 months after surgery, and 1 patient died of disease 24 months after diagnosis. On histologic sections, the tumors showed multinodular growth and were composed of variably cellular spindle to round-shaped cells with distinct brightly eosinophilic cytoplasm embedded within a myxoid stroma. One tumor showed overt smooth muscle differentiation. Cytologic atypia and mitotic activity ranged from minimal (2 cases) to high (1 case). By immunohistochemistry, the neoplastic cells expressed focal smooth muscle actin, h-caldesmon, and desmin in all tested cases. Skeletal muscle markers were negative. Next-generation sequencing detected nearly identical CRTC1::MRTFB gene fusions in all cases. We suggest that myxoid mesenchymal tumors with myogenic differentiation harboring a CRTC1::MRTFB fusion may represent a previously unrecognized, distinctive entity that involves soft tissue and bone. Continued identification of these novel myxoid neoplasms with myogenic differentiation will be important in determining appropriate classification, understanding biologic potential, and creating treatment paradigms.

MDM2 Amplification Status in a Cohort of Well-Characterized Myxofibrosarcoma: A Clinicopathologic Analysis of 22 Tumors.

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.

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature.

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.

Novel NCOA2/3-rearranged low-grade fibroblastic spindle cell tumors: A report of five cases.

Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33-86) with a median age of 42 and fairly even sex distribution = (male-to-female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in-frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow-up, 7.5 months; range, 2-19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low-grade NCOA2/3-rearranged fibroblastic spindle cell neoplasms.

Infantile Sinonasal Myxoma Is Clinically and Genetically Distinct From Other Myxomas of the Craniofacial Bones and From Desmoid Fibromatosis.

Sinonasal myxomas are rare benign tumors of the maxillary bone and sinus. There is published evidence that sinonasal myxomas occurring in children up to 3 years of age ("infantile sinonasal myxomas") are clinically distinctive and harbor Wnt signaling pathway alterations. Here, we characterized 16 infantile sinonasal myxomas and compared them to 19 maxillary myxomas and 11 mandibular myxomas in older patients. Clinical follow-up was available for 21 patients (46%) overall (median: 2.6 y; range: 4 mo to 21 y), including 10 of 16 infantile sinonasal myxomas (62%). None of the 8 resected infantile sinonasal myxomas recurred, despite positive margins in 6 of them. One incompletely resected infantile sinonasal myxoma underwent partial regression without additional treatment. In contrast, 4 of the 11 other myxomas with follow-up recurred (36%), including one that recurred twice. Imaging studies demonstrated all infantile sinonasal myxomas to be expansile lesions arising from the anterior maxillary bone adjacent to the nasal aperture, with peripheral reactive bone formation. Histologically, infantile sinonasal myxomas showed short, intersecting fascicles of bland fibroblastic cells with prominent stromal vessels. Examples with collagenous stroma showed some morphologic overlap with desmoid fibromatosis, although none showed infiltrative growth into adjacent soft tissue. Immunohistochemistry demonstrated nuclear ß-catenin expression in 14 of 15 infantile sinonasal myxomas (93%), in contrast to 4 of 26 other myxomas of craniofacial bones (15%). Smooth muscle actin was expressed in only 1 of 11 infantile sinonasal myxomas (9%). Next-generation sequencing was successfully performed on 10 infantile sinonasal myxomas and 7 other myxomas. Infantile sinonasal myxomas harbored CTNNB1 point mutations in 4 cases (D32Y, G34E, G34R, and I35S), and none harbored alterations to the phosphorylation sites T41 and S45 that are altered in 99% of CTNNB1 -mutant desmoid fibromatoses. Three tumors showed alterations consistent with biallelic APC inactivation. Three infantile sinonasal myxomas that showed strong nuclear ß-catenin expression were negative for CTNNB1 and APC alterations. Sequencing was negative for CTNNB1 or APC alterations in all 7 myxomas of craniofacial bones in older patients. Four of these myxomas in older patients (57%) showed copy number alterations, and all lacked known driving alterations. These findings support the notion that infantile sinonasal myxomas are clinically and genetically distinctive, and we propose the use of the diagnostic term "infantile sinonasal myxoma" to distinguish this tumor type from other myxomas of the craniofacial bones. Infantile sinonasal myxoma should be distinguished from desmoid fibromatosis because of its unique clinical presentation, more indolent clinical behavior, different morphology, different immunohistochemical profile, and different genetics. Given its indolent behavior even when marginally excised, infantile sinonasal myxoma can be managed with conservative surgery.

Novel EWSR1::GFI1B gene fusion in angiofibroma of soft tissue.

AIMS: Angiofibroma of soft tissue is a benign soft tissue tumour characterised by bland spindle cells and a distinct branching vascular network. The majority of soft tissue angiofibromas harbour AHRR::NCOA2 gene fusions. Here we present three cases of EWSR1::GFI1B-fused soft tissue tumours that are morphologically most reminiscent of soft tissue angiofibroma. METHODS AND RESULTS: All three cases presented in male patients with an age range of 35-78 years (median = 54 years). Two cases presented as subcutaneous nodules on the trunk (posterior neck and chest wall); one was an intramuscular foot mass. The tumours were unencapsulated nodules with infiltrative margins ranging from 2.2 to 3.4 cm in greatest dimension. Histologically, the tumours contained uniformly bland fibroblastic spindle cells with ovoid to fusiform nuclei and delicate cytoplasmic processes embedded in a myxoid to myxocollagenous stroma. All three cases were characterised by a thin-walled, branching vascular network evenly distributed throughout the tumour. Overt cytological atypia or conspicuous mitotic activity was absent. The spindle cells had an essentially null immunophenotype. By targeted RNA sequencing, an in-frame gene fusion between EWSR1 exons 1-7 and GFI1B exons 6-11 or 7-11 was detected in all three cases. The tumours were marginally excised. For all three cases, there were no documented local recurrence or distant metastases during a limited follow-up period of 6-10 months. CONCLUSIONS: We propose that EWSR1::GFI1B may represent a novel fusion variant of soft tissue angiofibroma.

Myxofibrosarcoma in adolescents and young adults: a clinicopathologic study of 17 cases.

Myxofibrosarcoma is a locally aggressive sarcoma that characteristically arises in the extremities of older patients. Cases arising at a younger age are rare, leading to diagnostic challenges. Our aim was to study the clinicopathologic features of myxofibrosarcoma in patients aged ≤40 years. Cases of myxofibrosarcoma and myxoid malignant fibrous histiocytoma arising in patients aged ≤40 years with clinical follow-up were collected from multiple institutions. Hematoxylin and eosin slides were evaluated for mitoses, necrosis, and epithelioid areas. Seventeen cases were identified (13 females, 4 males; 16-39 years; median 32 years), tumors ranged from 2.2 to 34 cm (median 4.1 cm). Anatomic sites included proximal extremity (9), distal extremity (4), trunk (1), and head/neck (3). Ten were superficial, and 6 were deep-seated. Three cases were predominantly epithelioid. In untreated resection specimens, 6 were FNCLCC grade 1, 4 grade 2, and 2 grade 3. Follow-up (6-204 months, median 36 months) revealed that 2 patients experienced local recurrences, 1 distant metastasis, and 2 patients both. The 5-year overall survival (OS) and event-free survival (EFS) were 84% and 55.9%, respectively. Tumor depth and necrosis were correlated with inferior OS (P = .025, P = .005), while tumor depth was also associated with worse EFS (P = <.001). We conclude that myxofibrosarcomas arising in adolescents and young adults show similar behavior compared to their older adult counterparts. Tumor depth and necrosis are poor prognostic factors in myxofibrosarcoma in this age group. Awareness that myxofibrosarcoma can rarely present in this population is important for accurate diagnosis.

DNA Methylation Profiling Distinguishes Adamantinoma-Like Ewing Sarcoma From Conventional Ewing Sarcoma.

Adamantinoma-like Ewing sarcoma (ALES) has traditionally been considered a variant of Ewing sarcoma because it generally harbors EWSR1::FLI1 fusions despite showing diffuse positivity for keratins and p40. However, it has become increasingly recognized that different tumors can have identical translocations, including shared fusions between carcinomas and sarcomas, raising questions as to whether ALES might represent a separate entity. Using methylation profiling, we further explored the relationship between Ewing sarcoma and ALES. The archives of multiple institutions were searched for candidate cases of ALES. DNA methylation profiling was performed and results were compared to corresponding data from conventional Ewing sarcoma. Twelve cases of ALES (5 previously reported) were identified in 10 men and 2 women (aged 20-72 years; median age, 41.5 years). Cases included tumors arising in the parotid gland (3), sinonasal cavity (2), submandibular gland (2), thyroid gland (1), neck (1), gingiva (1), hypopharynx (1), and mandible (1). Histologic review consistently showed sheets and nests of basaloid cells within a fibromyxoid or hyalinized stroma. All tumors were positive for at least 1 keratin and CD99 expression, whereas all 10 cases tested were positive for p63 or p40; S100 protein expression was noted in 2 cases. Cases harbored either EWSR1::FLI1 fusions (n = 6), FUS::FLI1 fusions (n = 1), and/or EWSR1 rearrangements (n = 6). Methylation profiling was successful in 11/12 cases evaluated. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) of DNA methylation data revealed a distinct methylation cluster for all 11 cases, including the tumor with the FUS::FLI1 fusion, which clearly segregated them from the conventional Ewing sarcoma. Follow-up (n = 11, 1-154 months) revealed that 4 patients experienced recurrence and 6 developed metastatic disease. ALES demonstrates a distinct methylation signature from conventional Ewing sarcoma. This finding adds to the distinctive immunoprofile of ALES, suggesting that these 2 tumors should be considered distinct entities rather than histologic extremes of the same disease.

Novel NONO::TFE3 fusion and ALK co-expression identified in a subset of cutaneous microcystic/reticular schwannoma.

Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene.

Keratin-positive giant cell-rich tumors of soft tissue with HMGA2::NCOR2 fusions.

BACKGROUND: Giant cell tumor of soft tissue (GCT-ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin-positive GCT-ST (KPGCT-ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven. METHODS: Cases diagnosed as GCT-ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed. RESULTS: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow-up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin-positive mononuclear cells with evenly admixed osteoclast-like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2::NCOR2 fusion was detected in all cases. CONCLUSIONS: Our findings support previously reported hypotheses that KPGCT-ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow-up data are limited, to date, KPGCT-ST appears to follow an indolent course.

Osteoid osteomas of the hands and feet: a series of 71 cases.

Osteoid osteomas typically arise in the long bones of extremities. Patients often report pain relieved by NSAIDS, and radiographic findings are often sufficient for diagnosis. However, when involving the hands/feet, these lesions may go unrecognized or misdiagnosed radiographically due to their small size and prominent reactive changes. The clinicopathologic features of this entity involving the hands and feet are not well-described. Our institutional and consultation archives were searched for all cases of pathologically confirmed osteoid osteomas arising in the hands and feet. Clinical data was obtained and recorded. Seventy-one cases (45 males and 26 females, 7 to 64 years; median 23 years) arose in the hands and feet, representing 12% of institutional and 23% of consultation cases. The clinical impression often included neoplastic and inflammatory etiologies. Radiology studies demonstrated a small lytic lesion in all cases (33/33), the majority of which had a tiny focus of central calcification (26/33). Nearly, all cases demonstrated cortical thickening and/or sclerosis and perilesional edema which almost always had an extent two times greater than the size of the nidus. Histologic examination showed circumscribed osteoblastic lesions with formation of variably mineralized woven bone with single layer of osteoblastic rimming. The most common growth pattern of bone was trabecular (n = 34, 48%) followed by combined trabecular and sheet-like (n = 26, 37%) with only 11 (15%) cases presenting with pure sheet-like growth pattern. The majority (n = 57, 80%) showed intra-trabecular vascular stroma. No case showed significant cytology atypia. Follow up was available for 48 cases (1-432 months), and 4 cases recurred. Osteoid osteomas involving the hands and feet follow a similar age and sex distribution as their non-acral counterparts. These lesions often present with a broad differential diagnosis and may initially be confused with chronic osteomyelitis or a reactive process. While the majority of cases have classic morphologic features on histologic exam, a small subset consists solely of sheet-like sclerotic bone. Awareness that this entity may present in the hands and feet will help pathologists, radiologists, and clinicians accurately diagnose these tumors.

Myoepithelioma, myoepithelioma-like, and chondroid soft-tissue tumors arising at acral sites: a review.

Myoepithelial neoplasms comprise a histologically and immunophenotypically diverse spectrum of entities. The following review is a comprehensive summary of acral lesions demonstrating myoepithelial-like and chondroid histomorphology, as well as recently described mimics that are diagnostically challenging to distinguish. The salient clinicopathologic, immunophenotypic, and molecular features of each entity are described.

Allowing Surgical Pathology Fellows to Release Preliminary Reports Increases Learner Independence and Satisfaction.

CONTEXT.­: Progressive independence in medicine is critical to building confidence and decisiveness in trainees. However, this can be difficult to accomplish in the strict regulatory environment of pathology. OBJECTIVE.­: To pilot and adopt a process whereby surgical pathology fellows independently manage a subset of cases and release preliminary reports. DESIGN.­: Upon program approval, board-certified surgical pathology fellows were eligible for preliminary report sign-out at their discretion. Eligible cases were sent from outside institutions for confirmatory review. Preliminary reports were viewable in the electronic medical record. Safety measures were used to ensure timely release of final reports by attending pathologists. RESULTS.­: Fellows participating in the pilot (n = 4) released 59 preliminary reports out of 101 cases reviewed (58%), with 1 potentially significant discrepancy between preliminary and final report. Turnaround time was not affected. The process was endorsed by all participants and adopted as standard practice. During the first year, eligible fellows (n = 8) released 123 preliminary reports out of 1260 cases reviewed (9.8%). There were no major diagnostic discrepancies and no effects on turnaround time. The number of preliminary reports released by each fellow was variable (range, 2-48; median, 8), likely a reflection of both external factors (number of trainees on service, volume) and trainee-specific factors (confidence, efficiency). CONCLUSIONS.­: Fellows showed good judgment when independently managing cases, with just 1 potentially significant discrepancy out of 182 cases (<1%). No patients were adversely impacted. Use of this process varied widely among fellows and may require closer monitoring and encouragement for fellows who are tentative about releasing preliminary reports.

The capillary lobule variant of radiation-associated angiosarcoma in the setting of breast cancer: A diagnostic pitfall.

AIM: Post-radiation angiosarcoma is an iatrogenic event seen in the setting of breast cancer treatment. Histopathologically, there are morphologic variants of angiosarcoma that mimic benign entities, including the capillary lobule variant of post-radiation angiosarcoma. We present the largest case series to date of this histopathologic variant of post-radiation angiosarcoma. METHODS AND RESULTS: Cases of the capillary lobule variant of post-radiation angiosarcoma from institutional/consultation archives from 2008 to June 2022 were reviewed. For inclusion, tumors had to occur in irradiated skin and exhibit a multi-lobular proliferation of tightly packed capillary-like vessels, as previously described in this variant. Prior ancillary studies were also reviewed. Eight cases met the criteria. All occurred in women treated with radiation for breast cancer (median age 75 years). All cases had similar findings, including a multi-lobular proliferation of tightly packed vessels, infiltrative cords, and atypical single endothelial cells. A conventional angiosarcoma pattern was also seen in five cases. All cases tested were positive for vascular markers (CD31, CD34, and/or ERG) and MYC. MYC amplification was shown by FISH in all cases tested. Smooth muscle actin (SMA) was positive in pericytes in the capillary lobules in all five cases tested and areas of conventional angiosarcoma in two of three cases. CONCLUSIONS: The capillary lobule variant of angiosarcoma is a rare and therefore potentially under-recognized variant of post-radiation angiosarcoma. The lobular architecture and SMA positivity may mimic benign vascular proliferations. Careful attention to histopathologic features and ancillary tests may facilitate accurate diagnosis.

Paratesticular Dedifferentiated Liposarcoma with Epithelioid Features: A Diagnostic Pitfall.

Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) represent a significant number of sarcomas arising within the paratesticular region. DDLPS is notorious for a broad histologic spectrum, but epithelioid morphology is rare. Herein, we describe a unique case of paratesticular DDLPS with prominent epithelioid features and molecular confirmation. The patient is 71-year-old-male who presented with multiple paratesticular masses. Morphologic review of the resection specimen revealed a biphasic adipocytic neoplasm consistent with DDLPS. Additionally, epithelioid foci with acinar and nested architecture and focal keratin expression were noted. These areas raised the possibility of a secondary neoplasm including sex cord stromal tumor, germ cell tumor, and paraganglioma. However, MDM2 immunohistochemistry and FISH showed these areas to express MDM2 and exhibit MDM2 amplification, respectively, confirming that they represented a component of DDLPS. This case further highlights the morphologic diversity of DDLPS as well as the utility of MDM2 studies.

Pleomorphic Liposarcoma: A Series of 120 Cases With Emphasis on Morphologic Variants.

Pleomorphic liposarcoma (PLPS) is a highly aggressive sarcoma comprising variable numbers of pleomorphic lipoblasts mixed with undifferentiated pleomorphic sarcoma (UPS)-like areas. Morphologic variants, such as myxofibrosarcoma-like or epithelioid, may cause diagnostic confusion, especially on a core biopsy, but there are few data on the prognostic significance of these features. A total of 120 PLPS biopsies and resection specimens were reviewed and catalogued based on the presence of myxofibrosarcoma-like, UPS-like, and epithelioid foci, in 10% increments. The clinical parameters were collected. Cases occurred in 75 males and 45 females, ranging from 8 to 98 years (median, 62.5 y). Cases arose in the extremities (n=72), trunk (n=32), head/neck (n=10), bone (n=4), mediastinum (n=1), or viscera (colon polyp, n=1). Of those with known depth (n=81), 40 were intramuscular, 34 were subcutaneous, and 7 arose in the dermis. Their sizes ranged from 1 to 24.5 cm (median, 7 cm). Of the patients with ≥1 month of follow-up (n=70), 5 had recurrence and 15 had metastasis. The 5-year overall survival and event-free survival rates were 66.2% and 63.1%, respectively. Tumors ≥5 cm had inferior overall survival compared with tumors <5 cm. The presence of epithelioid areas was also statistically significant in terms of poorer overall survival and event-free survival, while tumors with ≥50% undifferentiated pleomorphic-like areas had better overall survival. There was a trend towards poorer outcomes in tumors with necrosis (≥1%). PLPS is an aggressive adipocytic malignancy that is most commonly present in the extremities of older adults. The morphologic features of these tumors are diverse, and they may be mistaken for UPS or myxofibrosarcoma, carcinoma, and melanomas, particularly on biopsies. Tumor size, necrosis, and epithelioid morphology are associated with adverse prognosis.