Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Shaomin Hu, MD, PhD, gastrointestinal/liver pathology fellow, University of Chicago; and S. Emily Bachert, MD, breast pathology fellow, Brigham and Women’s Hospital, Boston.
Analysis of malignant diffuse mesothelioma in female cases
August 2020—The authors conducted a study in which they reviewed 354 cases of malignant diffuse mesothelioma in women from a database of 2,858 histologically confirmed cases. Pleural predominance was noted with 78 percent of pleural malignant mesotheliomas (MM) and 22 percent of peritoneal MM. The pleural tumors consisted of 72 percent epithelioid, 19 percent biphasic, and nine percent sarcomatoid variant. The peritoneal tumors consisted of 82 percent epithelioid, 13 percent biphasic, and five percent sarcomatoid. The immunohistochemical profile was typical of what is well accepted and previously described for MM. When examining tumor subtype and location, a trend toward epithelioid subtype and peritoneal location was found. However, it did not reach statistical significance. Age at time of diagnosis ranged from 19 to 93 years (mean, 60 years). The median age at time of diagnosis was 65 years for pleural MM and 52 years for peritoneal MM. Further review of age and histologic subtype showed no statistically significant difference in age between MM subtypes. Survival was greatest for the epithelioid variant, and this was magnified in the peritoneum. A majority of the study subjects were exposed to asbestos through household contact. Asbestosis and parietal pleural plaque were present in five percent and 50 percent of cases with data, respectively. Fiber analysis data were available in 67 cases, and 38 cases had elevated asbestos fiber burden. Tremolite was the most common asbestos fiber type detected. Commercial and noncommercial amphibole asbestos fibers were elevated in nearly equal numbers of cases.
Pavlisko EN, Liu B, Green C, et al. Malignant diffuse mesothelioma in women: a study of 354 cases. Am J Surg Pathol. 2020;44(3):293–304.
Correspondence: Dr. Elizabeth N. Pavlisko at elizabeth.pavlisko@duke.edu
A study of amyloidosis in surgically resected atrial appendages
Histomorphologic parameters of atrial appendages removed during the Cox-Maze procedure have been shown to correlate with recurrence of atrial fibrillation. While amyloid deposition has been noted within atrial appendages, the incidence and significance are not completely understood. More accurate amyloid typing methodologies and targeted pharmacotherapeutics have been developed, prompting pathologists to provide more detailed information about the type of amyloid identified in such samples. The authors conducted a study to characterize the morphologic characteristics of atrial amyloidosis, as well as its incidence and clinical significance. They queried tissue registry archives at the Mayo Clinic for atrial appendages removed during cardiac surgeries between 2010 and 2014 and abstracted from the medical record patient demographics and salient clinical findings. Typing of the amyloid protein was performed on a subset of cases by laser-capture microdissection with mass spectrometry-based proteomic analysis. The study included 383 atrial appendages from 345 consecutive patients (mean age, 69 years; range, 26–92 years). Amyloidosis was present in 46 percent of patients. A linear relationship was observed between age and presence of atrial amyloidosis. Women were more likely to have atrial amyloidosis. Two distinct morphologies of amyloidosis were observed: filamentous and nonfilamentous. They correlated perfectly with amyloid type (filamentous = AANF-type amyloid; nonfilamentous = ATTR-type amyloid). Filamentous deposits were observed in 91 percent of those with amyloidosis. The disorder was more likely to be found in the left atrial appendage than the right. Patients with atrial amyloidosis, irrespective of type, were more likely to have had a stroke or transient ischemic attack and more likely to have atrial arrhythmia preoperatively. In addition, those with atrial amyloidosis were more likely to have arrhythmia recur postoperatively than those who did not have atrial amyloidosis. The authors concluded that understanding the morphologic characteristics of AANF-type amyloid will allow for identification by light microscopy and obviate the need to use expensive ancillary typing techniques. A finding of nonfilamentous amyloidosis should still prompt confirmation of amyloid type so that targeted therapy may be employed.
Fayyaz AU, Bois MC, Dasari S, et al. Amyloidosis in surgically resected atrial appendages: a study of 345 consecutive cases with clinical implications. Mod Pathol. 2020;33(5):764–774.
Correspondence: Dr. Joseph J. Maleszewski at maleszewski.joseph@mayo.edu
Clinicopathologic analysis of chronic lymphocytic leukemia with TP53 gene alterations
TP53 alteration in chronic lymphocytic leukemia indicates a high-risk disease that is usually refractory to chemotherapy. It may be caused by deletion of 17p involving loss of the TP53 gene, which is found in a low percentage of patients at diagnosis but can be acquired as the disease progresses. Because patients may harbor the TP53 mutation without chromosome 17p deletion, consensus recommendations call for cytogenetic and polymerase chain reaction mutation analysis of TP53 in chronic lymphocytic leukemia. The authors conducted a single-institution retrospective study to investigate the clinicopathologic features of chronic lymphocytic leukemia with TP53 alterations and the utility of different diagnostic modalities to identify p53 alterations. Forty percent of chronic lymphocytic leukemia patients with TP53 alterations who were studied demonstrated atypical lymphocytes with cleaved/irregularly shaped nuclei or large atypical lymphoid cells with abundant cytoplasm in the peripheral blood, or both. Progression was also observed in lymph node and bone marrow samples—21 percent with Richter transformation and 33 percent with findings suggestive of the accelerated phase of chronic lymphocytic leukemia, including prominent proliferation centers or increased numbers of prolymphocytes, or both. However, presence of morphologic features suggestive of the accelerated phase had no effect on overall survival within the chronic lymphocytic leukemia group with TP53 abnormalities (p > .05). Similar to previous reports from others, a subset of patients with TP53 alterations were only identified by PCR mutation analysis (12 percent) or cytogenetic studies (14 percent). P53 immunostain positivity was found in approximately half the patients with TP53 alterations identified by either method, and it failed to identify any additional patients with p53 abnormalities. In summary, chronic lymphocytic leukemia patients with TP53 alterations frequently show atypical morphologic features. Use of multiple modalities to identify p53 abnormalities is recommended to ensure optimal sensitivity and specificity.
Liu YC, Margolskee E, Allan JN, et al. Chronic lymphocytic leukemia with TP53 gene alterations: a detailed clinicopathologic analysis. Mod Pathol. 2020;33(3):344–353.
Correspondence: Dr. Julia T. Geyer at jut9021@med.cornell.edu
Clinicopathological correlation of typical and atypical carcinoid tumors of lung
The authors conducted a study to correlate patient and histopathologic characteristics with long-term survival outcomes in neuroendocrine neoplasms of the lung. The study involved 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 pathology departments. Pathologists participating in the study critically reviewed all cases for clinical and pathological features and correlated them with clinical outcomes. Long-term follow-up was obtained for all patients and statistically analyzed to determine the significance of the parameters evaluated. Of the histopathological features analyzed, mitotic activity of four mitoses or more per 2 mm2, necrosis, lymphatic invasion, and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant, and they correlated with clinical outcomes. Based on their analysis, the authors determined that the separation of low- and intermediate-grade neuroendocrine neoplasms of the lung need to be readjusted in terms of mitotic count because the risk of overgrading these neoplasms exceeds 10 percent under current criteria. The authors also consider tumor size to be an important feature that should be taken into account when assessing these neoplasms. They concluded that a combination of grading and staging offer important clues for clinical outcomes.
Moran CA, Lindholm KE, Brunnström H, et al. Typical and atypical carcinoid tumors of the lung: a clinicopathological correlation of 783 cases with emphasis on histological features. Hum Pathol. 2020;98:98–109.
Correspondence: Dr. C. A. Moran at cesarmoran@mdanderson.org
MyoD1 expression in fibroepithelial stromal polyps
Fibroepithelial stromal polyps are benign polypoid mesenchymal lesions thought to arise from desmin-positive specialized stromal cells of the female genital tract. Although most cases are easily diagnosed by morphology alone, the morphology of fibroepithelial stromal polyps (FESP) is variable and can contain hypercellular stroma with numerous atypical desmin-positive cells simulating botryoid embryonal rhabdomyosarcoma (ERMS). The authors recently encountered a cellular FESP showing desmin expression and nuclear immunoreactivity for the skeletal muscle-associated transcription factor MyoD1. Although these lesions are widely known to express desmin, few studies have examined the expression of the more specific markers of skeletal muscle differentiation, myogenin and MyoD1. The authors conducted a study to examine desmin, MyoD1, and myogenin expression in a series of 25 FESPs. Desmin expression was present in 23 (92 percent); at least focal MyoD1 expression was present in 10 (40 percent); and all cases were negative for myogenin. Follow-up data were available for all 25 cases, and none recurred or behaved in a malignant fashion. The authors concluded that awareness of this potential IHC pitfall and careful morphologic evaluation should make it easy to distinguish MyoD1-positive FESP from botyroid ERMS in almost all instances.
Olson NJ, Fritchie KJ, Torres-Mora J, et al. MyoD1 expression in fibroepithelial stromal polyps. Hum Pathol. 2020;99:75–79.
Correspondence: Dr. A. L. Folpe at folpe.andrew@mayo.edu