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Cardiac myxomas with glandular elements are benign neoplasms that were first described by Anderson and Dmytryk in 1946 and are characterized histologically by a classical cardiac myxoma with benign glandular elements [5,6,7]. Cardiac myxomas are intracavitary endocardial lesions, that most commonly arise in the left atrium in the region of the fossa ovalis [1,4].
Grossly, cardiac myxomas can have either a solid or villiform appearance. The solid type may be globular or elongated with smooth, shiny, and sometimes undulating surfaces while the villiform type has irregular, often friable extensions [1]. Sectioning reveals a variegated, usually myxoid cut surface with areas of intratumoral hemorrhage. Secondary degenerative changes like necrosis, fibrosis, cystic change, and calcifications can also be seen [1].
Histologically, cardiac myxomas show the so-called myxoma cells that are cytologically bland stellate, ovoid, or plump spindle cells with eosinophilic cytoplasm embedded within a myxoid background [1]. These cells may occur either singly or in groups. When in groups, the cells can form cords, nests, or rings (perivascular rings) [1]. Glandular elements are very rare and are identified in less than 3% of all myxomas [1, 4]. The glands are predominantly located at the base of the tumor, without local infiltration [1]. In our case, histologic evaluation of the excised mitral valve leaflets did not show any evidence of infiltration by this lesion.
By immunohistochemistry (IHC), the myxoma cells are positive for calretinin in nearly all cases, with variable reactivity for NSE, S100, synaptophysin, SMA, and desmin [1,9]. Endothelial markers (e.g., CD34, CD31) are positive in the endothelium with variable reactivity reported in the myxoma cells [1].
The diagnosis of cardiac myxoma is usually straight forward but cardiac myxoma with glandular elements may be misdiagnosed due to its unusual histomorphological features and its rarity [5]. The new WHO classification of thoracic tumors classifies this benign neoplasm as a rare form of cardiac myxoma [1]. The glandular elements are considered to arise as a result of epithelial differentiation toward coelomic epithelium from the undifferentiated pluripotent subendocardial cells [5].
The main differential diagnosis for cardiac myxoma with glandular elements is metastatic adenocarcinoma, but the glands seen in cardiac myxoma lack nuclear atypia, mitotic figures, or necrosis [1,5]. Differentiation from metastatic adenocarcinoma can usually be achieved by a combination of clinical history, imaging, and ancillary studies [1]. Other differential diagnosis for cardiac myxoma includes papillary fibroelastoma, organizing thrombus, and myxoid cardiac sarcomas. Unlike in cardiac myxomas that most often arise in the left atrium in the region of the fossa ovalis, papillary fibroelastoma is usually an incidental finding that most commonly arises on the valves and has avascular papillae fibrovascular fronds [1]. Cardiac sarcomas can be differentiated from cardiac myxoma by cytologic atypia including nuclear pleomorphism and atypical mitotic figures. Additionally, sarcomas are typically negative for calretinin staining, in contrast to cardiac myxoma [5].
Most cardiac myxomas are sporadic, but up to 10% arise in the setting of Carney complex, an autosomal dominant disorder characterized by the constellation of myxomas (cardiac or extracardiac), endocrinopathy (Cushing syndrome and acromegaly), and spotty skin pigmentation [1,5]. Demonstration of lost PRKAR1A expression within the myxoma cells raises the possibility of underlying Carney complex, which should prompt clinical consideration of the syndrome and possibly include germline genetic testing as well [1].
Cardiac myxomas, regardless of their association with Carney complex, may be associated with peripheral tumor emboli, and up to 24% of all patients with cardiac myxomas die of its complications [2,3]. As seen in our patient, neurologic complications can be the initial manifestation of atrial myxoma. [8]. Neurological symptoms have been reported in 26% to 45% of patients and neurologic complications associated with atrial myxoma most frequently include cerebral infarct due to thrombus [8].
Surgical resection of atrial myxoma is curative in most patients. Our patient is currently approximately 10 months post-excision with no clinical or radiologic evidence of recurrence or any other malignancy.
It is important for pathologists to be aware that bland benign glandular elements can be present in cardiac myxomas and to be able to recognize this rare variant to avoid misdiagnosis of metastatic adenocarcinoma due to its unusual morphological features and to avoid unnecessary treatment.
References:
1. WHO Classification of Tumors Editorial Board. Thoracic tumors. Lyon (France): International agency of research on cancer; 2021. (WHO classification of tumors series, 5th edition.; Vol. 5).
2. Enzinger and Weiss’s Soft Tissue Tumors.7th ed. JR Goldblum, AL Folpe, and SW Weiss, eds. Philadelphia, PA: Elsevier, 2020: chap 31.
3. Boyacıoğlu K, Kalender M, Dönmez AA, Çayhan B, Tuncer MA. Outcomes following embolization in patients with cardiac myxoma. J Card Surg. 2017 Oct;32(10):621-626.
4. Zhang M, Ding L, Liu Y, Xue L. Cardiac myxoma with glandular elements: a clinicopathological and immunohistochemical study of five new cases with an emphasis on differential diagnosis. Pathol Res Pract. 2014 Jan;210(1):55-8.
5. Biswajit D, Vandadna R, Yookarin K, Prasad, KJ. Cardiac myxoma with glandular elements: An unusual histologic variant with a brief review of the literature. Journal of the Practice of Cardiovascular Sciences. 2019 Aug; 5(2):119-121
6. Nath D, Arava S, Ray R, Bhoje AK, Saxena R, Chaudhary SK. Immunohistochemical characterization of glandular elements in glandular cardiac myxoma: Study of six cases. Indian J Pathol Microbiol 2017;60:319-23.
7. Anderson WA, Dmytryk ET. Primary tumor of the heart containing epithelium-like elements. Am J Pathol 1946;22:337-49.
8. Lee VH, Connolly HM, Brown RD. Central Nervous System Manifestations of Cardiac Myxoma. Arch Neurol. 2007;64(8):1115–1120.
9. Acebo E, Val-Bernal JF, Gómez-Roman JJ. Thrombomodulin, calretinin and c-kit (CD117) expression in cardiac myxoma. Histol Histopathol. 2001 Oct;16(4):1031-6.
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