Document jyo1QdD8RZDZJ9D0p68KGEvNp

a!. 43. Neoplasms of the Pleura 601 ng th Figure 43.16. Pleural mesotheliomas may directly invade the pericardium and myocardium and may replace a significant to )h portion of the myocardium. In some instances, it is difficult to tell Figure 43.18. The lungs are coated by a thin rind of grayishif the pericardial involvement is an invasion or metastasis of a white tissue that represents a metastasis from a peritoneal pleural mesothelioma or a primary pericardial mesothelioma. mesothelioma. 3f id 5 S, Histologic Features and Classification :h of Pleural Mesothelioma lioid) mesothelioma, sarcomatoid (fibrous, sarcomatous) mesothelioma, and biphasic (mixed epithelial-sarcoma toid) mesothelioma. Desmoplastic mesothelioma, a form al Mesotheliomas show a wide variety of histologic patterns of sarcomatoid mesothelioma, is sometimes put into a s, and can resemble many other types of malignant neo separate subtype because it has such a unique morphol e plasms.:'S495"503 The application of immunohistochemistry ogy. A more detailed, expanded classification includes and electron microscopy to percutaneous and open epithelial mesothelioma, sarcomatoid mesothelioma, pleural biopsy-obtained tumor specimens or neoplastic biphasic mesothelioma, transitional mesothelioma, and h cells in pleural fluid is often necessary to render a diag pleomorphic mesothelioma. Within each of these catego i nosis of mesothelioma versus some other type of ries, especially that of epithelial mesothelioma, there are s neoplasm. additional histologic variants. Some of the more recogniz The simplest histologic classification of mesothelioma able variants are listed in Box 43.8 and are discussed encompasses three general categories: epithelial (epithe- separately below. Epithelial Mesothelioma Figure 43.17. Some epithelial mesotheliomas produce excess amounts of hyaluronic acid/proteoglycan, producing cysts filled with this material. Epithelial mesotheliomas are the most frequently diag nosed histologic type of mesothelioma and show a wide variation in histologic patterns (Box 43.8). It is not uncom mon to see more than one histologic pattern (subtype) of epithelial mesothelioma in any given mesothelioma. The more tissue one has to evaluate, the more likely one will see additional subtypes or a biphasic pattern. The tubulopapiilary pattern is the most common epi thelial subtype, being composed of relatively uniform cuboidal to rectangular cells with centrally located round nuclei that form distinct papillary structures containing a librovascujar core or small tubular structures when cut in cross section (Figs. 43.19 and 43.20). They may be associ ated with psammomatous calcification (Fig. 43.20), which is a nonspecific histologic feature and can be seen in any papillary neoplasm. Occasionally, individual tubulopapillary epithelial mesotheliomas are composed of large, 602 S.P. Hammar et al. Box 43.8. Epithelial Mesothelioma (Histologic Subtypes) Adenoid cystic Adenomatoid Bakery roll Clear cell Deciduoid Diffuse--not otherwise specified Gaucher-like Glandular/acinar Glomeruloid Blistiocytoid/epithelioid In association with excess amounts of hyaluronic acid or proteoglycan In situ Macrocystic Microcystic Mucin positive Placentoid Pleomorphic Poorly differentiated Rhabdoid Signet ring Single file Small cell Tubulopapillary Well-differentiated papillary more pleomorphic, cells with large nuclei and prominent nucleoli (Fig. 43.21). Epithelial mesotheliomas may form predominantly glandular/acinar structures that vary in size and shape and be histologically identical to adenocarcinomas Figure 43.20. This tubulopapillary epithelial mesothelioma was associated with numerous psammoma bodies. (Fig. 43.22). Sometimes the glandular/acinar epithelial mesotheliomas are composed of large columnar cells and resemble mucus-producing adenocarcinomas (Fig. 43.23). Mesotheliomas are not infrequently composed of round histiocytoid cells that vary in size. The smaller-sized cells have an epithelioid/histiocytoid morphology resem bling alveolar macrophages (Fig. 43.24). These cells have round nuclei and often large nucleoli and have abundant glassy eosinophilic cytoplasm on hematoxylin and eosin (H&E)-stained sections (Fig. 43.25). They not infre quently show periodic acid-Schiff (PAS)-positive staining that is sensitive to diastase, indicating glycogen in the cytoplasm of these cells. As we have reported,204 round cell mesothelioma encompasses a spectrum based on cell size, the large-cell end of which is referred to as a decidu oid mesothelioma. Deciduoid mesotheliomas are com- 4 < Figure 43.19. (A) This epithelial mesothelioma shows a tubulopapillary pattern. (B) Greater magnification showing fibrovascular cores that are covered by fairly uniform cuboidal epithelial cells. 603 Figure 43.24. Diffuse sheets of uniform round tumor cells resemble histiocytes. posed of cells that resemble progestationally stimulated endometrial stromal cells or ceils seen in placental tissue (i.e., deciduoid cells). Occasionally, round cell mesotheli omas exhibit a rhabdoid morphology with the nucleus of the cell toward the cell membrane with intracytoplasmic eosinophilic inclusions that represent intermediate fila ments (Fig. 43.26). Not infrequently, epithelial mesotheliomas are com posed of cystic structures ranging from an adenoid cystic morphology (Fig. 43.27) to cells organized as microcystic or macrocystic structures. The microcystic morphology appears as small cysts usually formed by somewhat atten uated squamoid-appearing cells (Fig. 43.28A). The same type of cell also forms the larger macrocystic structures (Fig. 43.28B). Some mesotheliomas are formed by cells that contain intracytoplasmic vacuoles that may impart a signet ring morphology (Fig. 43.29). RE 43.23. This epithelial mesothelioma is composed of tall suggestive of mucus production. Figure 43.25. This mesothelioma is composed of large round cells with mostly centrally located nuclei and abundant, glossy eosinophilic cytoplasm. This is referred to as a deciduoid meso thelioma because of its resemblance to decidualized endome trial stromal cells. 604 S.P. Hammar et al. Figure 43.26. Some round cell mesotheliomas are composed of cells exhibiting a rhabdoid morphology with nuclei at the edge of the cell in association with nodular-appearing eosinophilic cytoplasm. Figure 43.28. Epithelial mesotheliomas exhibit a wide-range of cystic patterns. (A) In this example, the mesothelioma is com posed of relatively small cystic structures formed by flattened, somewhat squamoid cells and by cuboidal cells. (B) This epithe lial mesothelioma is composed of flattened cells that form larger cystic structures. These cysts often contain a basophilic material in them that represents hyaluronic acid or proteoglycans. Figure 43.27. (A,B) Some epithelial mesotheliomas produce an adenoid-cystic pattern resembling adenoid-cystic carcinoma. Figure 43.29. Occasional mesotheliomas are formed by cells that contain intracytoplasmic vacuoles. Some cells have a signet ring morphology. 43. Neoplasms of the Pleura 605 Figure 43.30. An uncommon epithelial mesothelioma is com posed of small cells that resemble cells of neuroendocrine carcinomas. Figure 43.32. This epithelial mesothelioma produced large excess amounts of hyaluronic acid/proteoglycan that separates the neoplastic cells. Granular gray material surrounds the tumor cells. An uncommon type of epithelial mesothelioma referred to as a small cell mesothelioma closely resembles small cell neuroendocrine lung cancers. These mesotheliomas are usually arranged in diffuse solid sheets of small cells (Fig. 43.30) and are discussed in detail below (see Rare/ Unusual Mesotheliomas or Mesothelial Proliferations). A probable subtype of small cell mesothelioma is what we describe as glomeruloid mesothelioma, in which the small cells are arranged into structures that resemble renal glomeruli (Fig. 43.31). Approximately 10% to 20% of epithelial mesothelio mas produce excess amounts of hyaluronic acid or pro teoglycan (Figs. 43.32 and 43.33) that can be identified with an Alcian blue or colloidal iron stain. Pretreatment of the tissue sections with hyaluronidase usually decreases the intensity of, but often does not completely eliminate, the colloidal iron and Alcian blue staining (Fig. 43.33). Hyaluronic acid frequently crystallizes, which is best seen ultrastructurally (see Ultrastructural Features of Meso theliomas, below). Histologically, this material is grayish- blue and sometimes forms distinct crystalloid structures (Fig. 43.34). " In contrast to epithelial mesotheliomas that pro duce hyaluronic acid and proteoglycan, pulmonary adenocarcinomas contain intracellular mucosubstances that usually stain with a neutral mucosubstance stain such as PAS-diastase stain or with a slightly acidic mucosubstance stain such as Mayer's mucicarmine. We found that pulmonary adenocarcinomas that stain positive with PAS-diastase and mucicarmine also stain intensely positive with an Alcian blue or colloidal iron stain.505 Figure 43.31. (A,B) A variant of small cell mesothelioma is composed of small cells that produce structures that resemble glomeruli. 606 S.P. Hammar et al. Figure 43.34. Crystallized proteoglycan in the cystic structures of an epithelial mesothelioma. Figure 43.33. (A) AJcian blue-stained section shows intense bluish staining of the hyaluronic acid/proteoglycan. (B) When pretreated with hyaluronidase, the Alcian blue staining material is decreased in intensity or totally abolished. Some mesotheliomas are composed of relatively small, uniform cells that infiltrate in a single file arrangement and resemble lobular breast carcinomas. This type of pattern can be extensive (Fig. 43.35). Rare epithelial mesotheliomas are composed of relatively uniform cells that form concentric rolls (bakery roll pattern) (Fig. 43.36) or resemble chorionic villi (placentoid mesothelio mas) (Fig. 43.37). Rarely focal areas of squamous differ entiation (Fig. 43.38) occur, which perhaps is not surprising given that reactive nonneoplastic mesothelial cells show squamous metaplasia. Some epithelial mesotheliomas are composed of cells that have clear cytoplasm (clear cell mesotheliomas) (Fig. 43.39). This clearing is usually caused by glycogen, but has been reported by Ordonez Figure 43.35. (A,B) Some epithelial mesotheliomas are composed of cells that infiltrate stroma in a single file arrangement remi niscent of infiltrating lobular carcinoma of breast. ;ms of the Pleura $ *- J 607 3f a! is ?5' >- g Figure 43.38. (A,B) This epithelial mesothelioma shows focal squamous differentiation. Finding squamous epithelium does not necessarily indicate metastatic squamous carcinoma. Figure 43.39. Some epithelial mesotheliomas are composed of f Figure 43.37. Occasional epithelial mesotheliomas are com cells that have clear cytoplasm usually due to glycogen accumu posed of cells that form structures that resemble chorionic lation. These may resemble metastatic clear ceil carcinoma of : villi. the kidney. 608 S.P. Hammar et al. Figure 43.40. This mesothelioma is composed of poorly differ Figure 43.42. Fibrocollagenous tumor tissue in a pleural sarco entiated epithelial and spindle cells. matoid mesothelioma. et aid06 as being due to large numbers of cytoplasmic vesicles, the source of which is unknown. Finally, some mesotheliomas are composed of solid sheets of epitheli oid cells that are poorly differentiated (Figs. 43.40 and 43.41). These can be difficult to prove as having a mesothelial origin since they may not express immunohistochemical mesothelial markers other than broad-spectrum keratin and viinentin. Sarcomatoid Mesothelioma of the Pleura Pleural sarcomatoid MMs, as defined by either complete absence of epithelial tissue in an adequate biopsy or less than 10% of epithelial tissue,37 represent about 10% of pleural MMs, within a reported range of about 7% to 22%.37,211,503,507 The usual histologic pattern of sarcoma toid MM resembles that of a soft tissue fibrosarcoma or malignant fibrous histiocytoma (MFH).2il Some tumors may be extremely pleomorphic,503 whereas others are deceptively "bland" in appearance, posing difficulty in the distinction from benign fibrous pleuritis (Figs. 43.42 and 43.43). Other histologic patterns characteristic of sarcomatoid MM include leiomyoid differentiation508,309 (resembling leiomyosarcoma), and chondrosarcomatoid and osteosarcomatoid differentiation on rare occasions.38'211'303 Patterns resembling neurogenic sarcoma and rhabdomyosarcoma have also been described,211 as has a focal hemangiopericytic architecture (which requires dis tinction from a localized fibrous tumor of the pleura and from a pleural synovial sarcoma; see later discussion). In Figure 43.41. This mesothelioma is composed of plump, some what spindle-shaped cells with large nuclei and prominent nucleoli. (Alcian blue stain.) Figure 43.43. Pleural sarcomatoid mesothelioma. The neoplas tic tissue has a focal storiform architecture and the overall appearances resemble those of malignant fibrous histiocytoma.