Faculty Bibliography

Tenosynovial giant cell tumor (TGCT) is a benign neoplasm characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and translocation partners including collagen type VI alpha 3 chain (COL6A3) or S100 calcium-binding protein A10 (S100A10). Herein, we report three atypical TGCT cases with very unusual morphology comprising areas with increased cellular atypia, mitotic activity, and worrisome features that harbor unique non-CSF1 gene fusions. Anchored multiplex PCR (AMP) for next-generation sequencing utilizing a customized panel targeting 86 cancer-related genes was performed, and it identified novel non-CSF1-driven gene fusions: NIPBL-ERG, FN1-ROS1, and YAP1-MAML2. Screening of three control TGCTs with conventional morphology found translocations involving CSF1, with partner genes COL6A3, FN1, and newly identified KCNMA1. All novel fusions were further validated by reverse transcriptase-PCR (RT-PCR) and Sanger sequencing. Late and multiple local recurrences occurred in the atypical TGCTs, while no recurrences were reported in the conventional TGCTs. Our findings reveal that atypical TGCTs harbor gene fusions not implicating CSF1 and suggest that non-CSF1 fusions potentially confer greater propensity to recurrences and local aggressiveness while indicating the presence of alternate pathogenic mechanisms that warrant further investigation.

Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm that typically occurs in young adults. Juxtacortical or surface-type CMF are rarer still and we present the case of a surface-type CMF in a 78-year-old woman, with only one other case described in a patient of a similar age previously. This patient was an otherwise healthy woman who presented for evaluation of a palpable lump in the anterior proximal tibia. Initial radiographs obtained demonstrated a focal soft tissue fullness immediately anterior to the anterior cortex of the proximal tibia, which contained faint chondroid-like matrix internally. There was associated scalloping of the anterior tibial cortex. MRI confirmed the presence of a juxtacortical, enhancing lesion. Subsequent excisional biopsy was performed and histopathology demonstrated features, which was consistent with surface-type CMF. At a 6-month follow-up the patient remained free of recurrence. In a patient of this age, paraosteal chondrosarcoma should be excluded. Surface-type CMF, although rare, has been described in older patients and while it is unlikely to feature in a list of differential considerations on initial imaging, awareness of the entity is important.

PURPOSE/OBJECTIVE:To correlate the histopathologic appearances of resected long head of the biceps tendon (LHBT) specimens following biceps tenodesis, with pre-operative MRI and arthroscopic findings, with attention to the radiologically normal biceps. MATERIAL AND METHODS/METHODS:Retrospective analysis of patients who had undergone preoperative MRI, subsequent arthroscopic subpectoral tenodesis for SLAP tears and histopathologic inspection of the excised sample between 2013 and 16. Those with a normal MRI appearance or mildly increased intrasubstance signal were independently analyzed by 2 blinded radiologists. A blinded orthopedic surgeon and pathologist reviewed all operative imaging and pathologic slides, respectively. RESULTS:Twenty-three LHBT resected samples were identified on MRI as either normal (Reader 1 n = 15; Reader 2 n = 14) or demonstrating low-grade increased signal (Reader 1 n = 8; Reader 2 n = 9). Of these, 86.9% demonstrated a histopathological abnormality. 50% of samples with histopathological abnormality demonstrated normal appearance on MRI. The most common reported histopathology finding was myxoid degeneration (73.9%) and fibrosis (52.2%). The most common arthroscopic abnormality was fraying (18.2%) and erythema (13.6%). Utilizing histopathology as the gold standard, the two radiologists demonstrated a sensitivity of 35.0% v 42.9%, specificity of 66.7% v 100%, PPV of 87.5% v 100%, and NPV of 13.3% v 14.3%. Corresponding arthroscopic inspection demonstrated a sensitivity of 31.6%, specificity of 66.6%, PPV 85.7% and NPV of 13.3%. There was moderate agreement between the two radiologists, κ = 0.534 (95% CI, 0.177 to 0.891), p = 0.01. CONCLUSION/CONCLUSIONS:Histopathological features of low grade tendinosis including mainly myxoid degeneration and fibrosis are frequently occult on MR imaging.

Purpose: To retrospectively correlate the MR imaging, arthroscopic and histopathologic appearance of resected long of biceps tendon samples following biceps tenodesis. Materials and Methods: Following IRB approval, a retrospective review of 63 cases between 2013 and 2016 was performed in patients who had undergone preoperative shoulder MRI, arthroscopy and long head of the biceps tenotomy and tenodesis followed by histopathologic inspection of the excised sample. Independently, two blinded radiologists reviewed the MRI appearance of the biceps tendon. Biceps tendon split tearing, subluxation and dislocation were described separately. A blinded shoulder orthopedist and a pathologist with bone and soft tissue specialization reviewed all operative imaging and pathologic slides respectively. Statistical analysis including inter-rater agreement was performed to assess concordance in the degree of agreement among pathologist, surgeon and radiologist. Results: Of the 63 samples of biceps tissue analyzed 59 demonstrated a histopathological abnormality pertaining to the tendon or tenosynovium. Four samples were reported as histopathologically normal.13/59 (22%) of samples with histopathological abnormality demonstrated normal appearance on MR imaging. Of these, the most common reported pathology finding was mild fibrosis and/or myxoid degeneration. Histopatholgical abnormalities of the tendon positively correlating with MRI and arthoscopic findings included intra-tendinous granulation tissue, severe myxoid degeneration and fibrocartilage tendinous tissue. Conclusion: A significant number of patients with histopathological evidence of tendinosis including mild fibrosis and myxoid degeneration demonstrate no abnormality on MRI

PURPOSE/OBJECTIVE: The role of radiation therapy in the treatment of myoepithelial carcinoma (MC) is unknown. We present a case of a high-grade soft-tissue MC in a pediatric patient and retrospectively examine the effect of postoperative radiation on survival in patients with MC. MATERIALS AND METHODS: Our patient was treated with 4 cycles of ifosfamide, cisplatin, and etoposide followed by 3 cycles of ifosfamide vincristine and etoposide. Radiation was delivered to a total dose of 5580 cGy in 180 cGy/fraction to the surgical bed with a 2 cm margin starting after the third cycle of chemotherapy. The Surveillance, Epidemiology, and End Results (SEER) registry database was queried for cases of surgically resected MC. Retrospective analysis was performed with the endpoint of overall survival (OS). RESULTS: Two hundred thirty-four cases of MC were identified; for 62 of these cases, the grade of the tumor wasidentified. Of these 62 patients, 27 received postoperative radiation. OS was improved with adjuvant radiation therapy in patients with grade III or IV MC (P<0.01) as determined by the log-rank test. CONCLUSIONS: This analysis of SEER data showed an OS benefit with adjuvant radiation therapy in the treatment of high-grade MC. Physicians should report all cases of MC to improve clinical decision making in the treatment of this rare disease.

Leadership and management training during pathology residency have been identified repeatedly by employers as insufficient. A 1-month rotation in clinical laboratory management (CLM) was created for third-year pathology residents. We report on our experience and assess the value of this rotation. The rotation was one-half observational and one-half active. The observational component involved being a member of department and laboratory service line leadership, both at the departmental and institutional level. Observational participation enabled learning of both the content and principles of leadership and management activities. The active half of the rotation was performance of a project intended to advance the strategic trajectory of the department and laboratory service line. In our program that matriculates 4 residents per year, 20 residents participated from April 2010 through December 2015. Their projects either activated a new priority area or helped propel an existing strategic priority forward. Of the 16 resident graduates who had obtained their first employment or a fellowship position, 9 responded to an assessment survey. The majority of respondents (5/9) felt that the rotation significantly contributed to their ability to compete for a fellowship or their first employment position. The top reported benefits of the rotation included people management; communication with staff, departmental, and institutional leadership; and involvement in department and institutional meetings and task groups. Our 5-year experience demonstrates both the successful principles by which the CLM rotation can be established and the high value of this rotation to residency graduates.