Publications by authors named "Lucas R Massoth"

12 Publications

  • Page 1 of 1

Case 6-2021: A 65-Year-Old Man with Eye Pain and Decreased Vision.

N Engl J Med 2021 Feb;384(8):745-753

From the Department of Neurology, Beth Israel Deaconess Medical Center (M.A.B.), the Departments of Neurology (B.K.C.), Radiology (J.M.R.), Neuro-oncology (I.C.A.-R.), and Pathology (L.R.M.), Massachusetts General Hospital, and the Departments of Neurology (B.K.C.), Radiology (J.M.R.), Neuro-oncology (I.C.A.-R.), and Pathology (L.R.M.), Harvard Medical School - all in Boston.

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http://dx.doi.org/10.1056/NEJMcpc2027089DOI Listing
February 2021

Smooth Muscle Conditions of the Chest: A Clinical, Radiologic, and Pathologic Review.

J Thorac Imaging 2020 Nov 6. Epub 2020 Nov 6.

Department of Radiology, Mayo Clinic, Jacksonville, FL.

Smooth muscle conditions of the chest have diverse clinical and imaging manifestations and may involve nearly every thoracic structure. Differentiation among these conditions requires the integration of clinical, radiologic, and histopathologic data. Histologic examination in conjunction with immunohistochemistry is essential for differentiation from other spindle cell neoplastic mimics. Familiarity with these entities will ensure the inclusion of smooth muscle conditions in the differential diagnosis of thoracic soft tissue lesions and potentially guide the clinician in appropriate management. We review the clinical, imaging, and histopathologic features of thoracic smooth muscle-related conditions organized by the anatomic structures affected.
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http://dx.doi.org/10.1097/RTI.0000000000000567DOI Listing
November 2020

Pan-Cancer Landscape Analysis Reveals Recurrent - Gene Fusion in Aggressive Histologic Subtypes of Thymoma.

JCO Precis Oncol 2020 26;4. Epub 2020 Feb 26.

Foundation Medicine, Cambridge, MA.

Purpose: Thymomas are epithelial neoplasms that represent the most common thymic tumors in adults. These tumors have been shown to harbor a relatively low mutational burden. As a result, there is a lack of genetic alterations that may be used prognostically or targeted therapeutically for this disease. Here, we describe a recurrent gene rearrangement in type B2 + B3 thymomas.

Patients And Methods: A single index case of thymoma was evaluated by an RNA-based solid fusion assay. Separately, tissues from 255,008 unique advanced cancers, including 242 thymomas, were sequenced by hybrid capture-based next-generation DNA sequencing/comprehensive genomic profiling of 186 to 406 genes, including lysine methyltransferase 2A () rearrangements, and a portion were evaluated for RNA of 265 genes. We characterized molecular and clinicopathologic features of the pertinent fusion-positive patient cases.

Results: We identified 11 patients with thymomas harboring a gene fusion of and mastermind-like transcriptional coactivator 2 (). Fusion breakpoints were identified between exon 8, 9, 10, or 11 of and exon 2 of . Fifty-five percent were men, with a median age of 48 years at surgery (range, 29-69 years). Concurrent genomic alterations were infrequent. The 11 thymomas were of B2 or B3 type histology, with 1 case showing foci of thymic carcinoma. The frequency of - fusion was 4% of all thymomas (10 of 242) and 6% of thymomas of B2 or B3 histology (10 of 169).

Conclusion: - represents the first recurrent fusion described in type B thymoma. The fusion seems to be specific to type B2 and B3 thymomas, the most aggressive histologic subtypes. The identification of this fusion offers insights into the biology of thymoma and may have clinical relevance for patients with disease refractory to conventional therapeutic modalities.
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http://dx.doi.org/10.1200/PO.19.00288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446345PMC
February 2020

Comparison of RNA In Situ Hybridization and Immunohistochemistry Techniques for the Detection and Localization of SARS-CoV-2 in Human Tissues.

Am J Surg Pathol 2021 01;45(1):14-24

Departments of Pathology.

Coronavirus disease-19 (COVID-19) is caused by a newly discovered coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although SARS-CoV-2 is visualized on electron microscopy, there is an increasing demand for widely applicable techniques to visualize viral components within tissue specimens. Viral protein and RNA can be detected on formalin-fixed paraffin-embedded (FFPE) tissue using immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. Herein, we evaluate the staining performance of ISH for SARS-CoV-2 and an IHC directed at the SARS-CoV nucleocapsid protein and compare these results to a gold standard, tissue quantitative real-time polymerase chain reaction (qRT-PCR). We evaluated FFPE sections from 8 COVID-19 autopsies, including 19 pulmonary and 39 extrapulmonary samples including the heart, liver, kidney, small intestine, skin, adipose tissue, and bone marrow. We performed RNA-ISH for SARS-CoV-2 on all cases with IHC for SARS-CoV and SARS-CoV-2 qRT-PCR performed on selected cases. Lungs from 37 autopsies performed before the COVID-19 pandemic served as negative controls. The ISH and IHC slides were reviewed by 4 observers to record a consensus opinion. Selected ISH and IHC slides were also reviewed by 4 independent observers. Evidence of SARS-CoV-2 was identified on both the IHC and ISH platforms. Within the postmortem lung, detected viral protein and RNA were often extracellular, predominantly within hyaline membranes in patients with diffuse alveolar damage. Among individual cases, there was regional variation in the amount of detectable virus in lung samples. Intracellular viral RNA and protein was localized to pneumocytes and immune cells. Viral RNA was detected on RNA-ISH in 13 of 19 (68%) pulmonary FFPE blocks from patients with COVID-19. Viral protein was detected on IHC in 8 of 9 (88%) pulmonary FFPE blocks from patients with COVID-19, although in 5 cases the stain was interpreted as equivocal. From the control cohort, FFPE blocks from all 37 patients were negative for SARS-CoV-2 RNA-ISH, whereas 5 of 13 cases were positive on IHC. Collectively, when compared with qRT-PCR on individual tissue blocks, the sensitivity and specificity for ISH was 86.7% and 100%, respectively, while those for IHC were 85.7% and 53.3%, respectively. The interobserver variability for ISH ranged from moderate to almost perfect, whereas that for IHC ranged from slight to moderate. All extrapulmonary samples from COVID-19-positive cases were negative for SARS-CoV-2 by ISH, IHC, and qRT-PCR. SARS-CoV-2 is detectable on both RNA-ISH and nucleocapsid IHC. In the lung, viral RNA and nucleocapsid protein is predominantly extracellular and within hyaline membranes in some cases, while intracellular locations are more prominent in others. The intracellular virus is detected within pneumocytes, bronchial epithelial cells, and possibly immune cells. The ISH platform is more specific, easier to analyze and the interpretation is associated with the improved interobserver agreement. ISH, IHC, and qRT-PCR failed to detect the virus in the heart, liver, and kidney.
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http://dx.doi.org/10.1097/PAS.0000000000001563DOI Listing
January 2021

Peripheral blood morphologic findings in patients with COVID-19.

Int J Lab Hematol 2020 Dec 30;42(6):e248-e251. Epub 2020 Jul 30.

Pathology Department, Massachusetts General Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1111/ijlh.13300DOI Listing
December 2020

Pan-sarcoma genomic analysis of KMT2A rearrangements reveals distinct subtypes defined by YAP1-KMT2A-YAP1 and VIM-KMT2A fusions.

Mod Pathol 2020 11 27;33(11):2307-2317. Epub 2020 May 27.

Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.

Sarcomas are driven by diverse pathogenic mechanisms, including gene rearrangements in a subset of cases. Rare soft tissue sarcomas containing KMT2A fusions have recently been reported, characterized by a predilection for young adults, sclerosing epithelioid fibrosarcoma-like morphology, and an often aggressive course. Nonetheless, clinicopathologic and molecular descriptions of KMT2A-rearranged sarcomas remain limited. In this study, we identified by targeted next-generation RNA sequencing an index patient with KMT2A fusion-positive soft tissue sarcoma. In addition, we systematically searched for KMT2A structural variants in a comprehensive genomic profiling database of 14,680 sarcomas interrogated by targeted next-generation DNA and/or RNA sequencing. We characterized the clinicopathologic and molecular features of KMT2A fusion-positive sarcomas, including KMT2A breakpoints, rearrangement partners, and concurrent genetic alterations. Collectively, we identified a cohort of 34 sarcomas with KMT2A fusions (0.2%), and YAP1 was the predominant partner (nā€‰=ā€‰16 [47%]). Notably, a complex rearrangement with YAP1 consistent with YAP1-KMT2A-YAP1 fusion was detected in most cases, with preservation of KMT2A CxxC-binding domain in the YAP1-KMT2A-YAP1 fusion and concurrent deletions of corresponding exons in KMT2A. The tumors often affected younger adults (age 20-66 [median 40] years) and histologically showed variably monomorphic epithelioid-to-spindle shaped cells embedded in a dense collagenous stroma. Ultrastructural evidence of fibroblastic differentiation was noted in one tumor examined. Our cohort also included two sarcomas with VIM-KMT2A fusions, each harboring concurrent mutations in CTNNB1, SMARCB1, and ARID1A and characterized histologically by sheets of spindle-to-round blue cells. The remaining 16 KMT2A-rearranged sarcomas in our cohort exhibited diverse histologic subtypes, each with unique novel fusion partners. In summary, KMT2A-fusion-positive sarcomas most commonly exhibit sclerosing epithelioid fibrosarcoma-like morphology and complex YAP1-KMT2A-YAP1 fusions. Cases also include rare spindle-to-round cell sarcomas with VIM-KMT2A fusions and tumors of diverse histologic subtypes with unique KMT2A fusions to non-YAP1 non-VIM partners.
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http://dx.doi.org/10.1038/s41379-020-0582-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581494PMC
November 2020

Massive Splenomegaly from Disseminated Infection.

N Engl J Med 2020 Mar;382(11):1041

Massachusetts General Hospital, Boston, MA

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http://dx.doi.org/10.1056/NEJMicm1905550DOI Listing
March 2020

Secondary histiocytic sarcoma with BRAF mutation after T-cell acute lymphoblastic leukemia in a very young child with dramatic response to dabrafenib and trametinib.

Pediatr Blood Cancer 2020 05 9;67(5):e28200. Epub 2020 Feb 9.

Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1002/pbc.28200DOI Listing
May 2020

Multiple calcifying fibrous pseudotumors of the pleura: ultrastructural analysis provides insight on mechanism of dissemination.

Ultrastruct Pathol 2019 ;43(4-5):154-161

Departments of Pathology (L.R.M., M.K.S., I.C., R.L.K.) and Radiology (B.P.L.), Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Calcifying fibrous pseudotumor (CFP) is a rare, benign soft tissue tumor that may uncommonly arise in the pleura. These tumors can show multifocal dissemination across the pleural surface, but the mechanism underlying this dissemination is unclear. Review of previously reported cases of pleural CFP demonstrates a strong predilection for basal and diaphragmatic pleural surfaces, and a significantly higher rate of multifocality compared with other locations. We present a 59-year-old male with multiple CFP of the pleura. Reactive-appearing adhesions spanning the pleural surfaces were present, and by electron microscopy, were involved by tumor. We suggest this is the likely mode of dissemination across the pleural surfaces.
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http://dx.doi.org/10.1080/01913123.2019.1687631DOI Listing
April 2020

Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation.

N Engl J Med 2019 Jun;380(26):2564-2573

From the Department of Medicine, Northwestern Memorial Hospital, and the Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago (M.G.I.); and the Departments of Medicine (T.A.L., N.B., G.D.L.) and Pathology (L.R.M.), Massachusetts General Hospital, and the Departments of Medicine (T.A.L., N.B., G.D.L.) and Pathology (L.R.M.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1904040DOI Listing
June 2019

Case 13-2019: A 54-Year-Old Man with Alcohol Withdrawal and Altered Mental Status.

N Engl J Med 2019 Apr;380(17):1657-1665

From the Departments of Medicine (A.Z.F.), Radiology (A.M.), Psychiatry (M.N.), and Pathology (L.R.M.), Massachusetts General Hospital, and the Departments of Medicine (A.Z.F.), Radiology (A.M.), Psychiatry (M.N.), and Pathology (L.R.M.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1900591DOI Listing
April 2019

Case 7-2019: A 73-Year-Old Woman with Swelling of the Right Groin and Fever.

N Engl J Med 2019 Feb;380(9):859-868

From the Departments of Medicine (J.D.S., M.S.H.), Radiology (S.H.T.), and Pathology (L.R.M.), Massachusetts General Hospital, and the Departments of Medicine (J.D.S., M.S.H.), Radiology (S.H.T.), and Pathology (L.R.M.), Harvard Medical School - both in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1816408DOI Listing
February 2019