REVIEW ARTICLE
Myoepithelial Carcinoma of the Lung: A Review Lauren E. Rosen, MD,* Rohit I. Singh, MD,* Michael Vercillo, MD,w and Paolo Gattuso, MD*
Abstract: Primary myoepithelial carcinoma of the lung is a rare neoplasm with only 8 cases reported in the English literature to date. Myoepithelial carcinomas of the lung are thought to arise from submucosal bronchial glands and have morphologic features similar to their salivary gland counterparts. The pathologic features and immunohistochemical profile of this tumor have not yet been summarized in the literature. Our objective is to review the clinicopathologic features and immunohistochemistry of these tumors. Key Words: myoepithelial carcinoma, immunohistochemistry, salivary-type lung tumors (Appl Immunohistochem Mol Morphol 2015;23:397–401)
P
rimary salivary-type tumors of the lung, including myoepithelial carcinoma, are rare. Myoepithelial carcinomas primarily occur in the salivary glands, parotid, and breast.1 Myoepithelial carcinomas arising in soft tissue have also been reported.2 Primary salivary glandtype tumors of the lung are thought to arise from submucosal bronchial glands in the lower respiratory tract and have morphologic features similar to those of their salivary gland counterparts.3 Myoepithelial tumors, including myoepithelioma and myoepithelial carcinoma show myoepithelial differentiation and lack a ductal component. The first case of myoepithelial carcinoma was described by Higashiyama et al in 1998 and to date, there are only 8 cases of myoepithelial carcinoma reported in the English literature.4–10
DISCUSSION The clinical features of the 8 reported cases and 1 case from our institution are summarized in Table 1. With the exception of 1 case in which little clinical information is available, patients ranged in age from 58 to 76 years with a mean age of 60 years. Five patients were male and 3 were female. Of the 7 cases where race was specified, 2 patients were white, 2 were Japanese, and 3 were described only as Asian.4,6–8,10 The majority of patients (71%) had a smoking history. Four tumors were uniReceived for publication March 24, 2014; accepted May 5, 2014. From the Departments of *Pathology; and wCardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, IL. The authors declare no conflict of interest. Reprints: Lauren E. Rosen, MD, Department of Pathology, Rush University Medical Center, 1750 W Congress Parkway, Suite 532, Chicago, IL 60612 (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
Appl Immunohistochem Mol Morphol
focal,4,5,7,8 one was described as a consisting of confluent multinodular tumor.6 Most tumors were endobronchial (4 of 7) and the remaining were peripherally located. Tumors ranged in size from 1.5 to 13 cm with a mean size of 4.3 cm. All patients underwent surgical resection by wedge resection, lobectomy, or pneumonectomy. Seven cases showed metastases, involving the lung, liver, brain, or soft tissue.4–6,8–10 One patient had a lung metastasis and diagnosis9 and 1 patient presented with 3 metastatic lung lesions 15 months following initial resection.10 Two patients with metastatic disease died of disease at 11 and 60 months postoperatively, respectively.4,8 One patient died of other causes at 14 months.4 Two patients were reported to be alive with disease at 7 and 36 months, respectively,6,9 and 3 patients were reported to be without evidence of disease at 3, 10, and 15 months postoperatively.7,10 The imaging features of myoepithelial carcinoma of the lung are not well described in the literature. Imaging studies were performed in 7 of the 8 reviewed cases.4–10 In all but 2 cases, both chest x-ray and chest computed tomography (CT) were performed.4–7,9,10 On chest x-ray, the lesion is described in all cases as a nodule or shadow. By chest CT, the tumor was described in 1 case as a smoothly circumscribed heterogenous mass,9 in a second as a solid spiculated mass,8 and in a third as a nodular shadow with irregular borders.7 In 1 patient with metastatic lung lesions, CT demonstrated well-circumscribed nodules.10 Two lesions were not further characterized by CT.4,6 Two lung lesions, 1 primary and 1 metastatic were hypermetabolic by positron emission tomography.7,10 The patient from our institution was found to have a nodule on chest x-ray, and a subsequent chest CT showed a spiculated mass. The lesion was hypermetabolic by positron emission tomography with a standard uptake value of 6.6. Pathologic features, available in 8 cases including 1 case from our institution, are summarized in Table 2. Gross findings are available in 5 cases. The majority of tumors are described as well-circumscribed and nodular with a solid white cut surface. One case showed gross necrosis and cyst formation.6 The histology varied among cases. The majority of tumors were biphasic; composed of epithelioid, plasmacytoid, squamoid, spindle, and or clear cells. The stroma was described in only 2 cases, as myxoid in both.7–8 Our case showed cords and nests of oval to fusiform clear cells with small single nucleoli and minimal atypia arranged around a central hyalinized matrix (Fig. 1). Tanahashi et al8 described a case with similar morphology, composed of a central area containing
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TABLE 1. Clinical Description of Reported Cases Age/ Sex
Race
Smoking History
Higashiyama et al4 Higashiyama et al4 Sekine et al5 Miura et al6
58/M
Japanese
Yes
RUL, endobronchial
58/M
Japanese
Yes
LUL, endobronchial
NA 46/M
NA Asian
NA NA
Masuya et al7
48/M
Asian
Yes
NA Right mainstem bronchus LLL, endobronchial
LLL lobectomy
15
Tanahashi et al8 Sarkaria et al9
76/M
Asian
Yes
LLL, peripheral
LLL wedge resection
22
63/F
NA
No
60/F
White
No
RLL wedge resection, excision LLL wedge resection
130
Hysi et al10
RLL, peripheral and pleural LLL, peripheral
This study
72/F
White
Yes
RUL, endobronchial
RUL wedge resection
15
References
Location
Tumor Size (mm)
Surgery Sleeve bilobectomy (RUL, RML) LUL sleeve lobectomy
38 60
NA Right pneumonectomy
NA 65
25
Metastases
Outcome
Soft tissue left arm DOC, 14 mo Liver DOD, 60 mo Yes NA LLL NED, 7 mo AWD, 7 mo No NED, 15 mo Brain DOD, 11 mo RLL (pleura) and AWD, liver 36 mo LLL and RLL NED, 10 mo No NED, 7 mo
AWD indicates alive with disease; DOC, dead of other cause; DOD, dead of disease; HPF, high-power field; LLL, left lower lobe; LUL, left upper lobe; NA, not available; NED, no evidence of disease; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.
eosinophilic polygonal and clear cells arranged in a cordlike and reticular pattern within an abundant myxohyaline stroma. The periphery of this lesion, in contrast to our case, was hypercellular and composed of solid lobules of atypical cells with a high mitotic index and focal comedonecrosis. One case was composed of spindle cells (based only on the published photograph) and the other describes only the presence of a fibrous capsule.6,9 Two endobronchial tumors showed invasion into the bronchial mucosa with associated bronchial ulceration.4,6 Cyst formation was reported in 2 tumors, both of which were composed of spindle and plasmacytoid cells.1,6 Necrosis
was described in 3 cases,4,6,9 and the mitotic index ranged from 4 to 32/10 HPF (mean 13/10 HPF).6–8,10 The immunohistochemical profile of myoepithelial carcinoma of the lung has yet to be established. Normal myoepithelial cells express CK14, SMA, MSA, calponin, SMMS, and p63.11 The diagnosis of salivary gland myoepithelial carcinoma requires reactivity for cytokeratin and at least one other myoepithelial cell marker, including calponin, CD10, GFAP, SMA, or SMMS.12 SMA, calponin, SMMS, and GFAP are specifically but inconsistently expressed by salivary gland tumors with myoepithelial differentiation. S100, p63, and vimentin are
TABLE 2. Pathologic Features of Reported Cases References
Gross Appearance
Cell Type
Other Histologic Features
Higashiyama et al4
NA
Biphasic, spindle, and plasmacytoid cells
Higashiyama et al4 Miura et al6
NA
Biphasic, squamoid, and plasmacytoid cells Biphasic, spindle, and plasmacytoid cells
Masuya et al7
White, solid, multinodular with focal necrosis, and cyst formation NA
Tanahashi et al8 Well circumscribed, white, multilobulated, solid
Sarkaria et al9 Hysi et al10 This study
Well circumscribed, nodular Well-circumscribed, nodular White, solid, well-circumscribed
Interspersed microcystic areas, necrosis, hemorrhage. Open chromatin, indistinct nuclear membranes, inconspicuous nucleoli Plasmacytoid cells with eosinophilic cytoplasm
Spindled (based on published photograph)
Oval nuclei, focal macronuclei and multinucleated tumor cells, myxoid stroma Biphasic, epithelioid, and clear cells Central hyaline myxocellular area with cords of cells and peripheral hypercellular area with solid lobules of atypical cells and focal necrosis Fibrous capsule, necrosis (20%) Biphasic, spindle cells, and clear cells Minimal atypia, oval nuclei Oval to fusiform clear cells Minimal atypia, prominent nucleoli, hyalinized stroma
Mitoses/ 10 HPFs Sporadic
Numerous 13 5 32
NA 9 4
NA indicates not available.
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Myoepithelial Carcinoma of the Lung
FIGURE 1. Myoepithelial carcinoma. A, Radiating cords and nests of tumor cells surrounding a centrally hyalinized matrix. B, Radiating cords of fusiform tumor cells. C and D, The tumor cells are oval to fusiform with round to oval nuclei, fine vesicular chromatin, small nucleoli, and clear cytoplasm. The tumor was endobronchial.
sensitive but nonspecific markers. Cytokeratins are variably expressed by myoepithelial carcinomas of the salivary gland, with AE1/AE3 being the most sensitive. The tumors are typically negative for CK7, CEA, CD117, and desmin and have been reported to show weak EMA positivity.11,13 The immunoprofile of the reported cases of myoepithelial cell carcinoma of the lung, including our case, is summarized in Table 3. Of the 9 cases reviewed, keratin positivity was present in 6 of 8, or 75% of cases; 5 of 6 for AE1/AE3 and 2 of 2 for CK8/18 (Fig. 2). Tumor cells were positive for SMA (6 of 7), S100 (5 of 7), SMMS (2 of 2), p63 (2 of 2), and CD99 (2 of 2). Less frequent positivity was reported with EMA (3 of 6), calponin (2 of 4), CD10 (1 of 2), vimentin (4 of 7), GFAP (2 of 6), and desmin (2 of 8). Three cases describe the tumor cells as PAS positive and PAS-D negative.4,8 Tumor cells with squamoid differentiation; preset focally in 1 case; were positive for EMA, AE1/AE3, and CEA.4 In one of the 2 cases in which myxoid stroma was described, the stroma was positive for Alcian blue pH 2.5 and metachromatic with toluene blue.8 Copyright
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The differential diagnosis of myoepithelial carcinoma is broad and includes other salivary-type tumors such as myoepithelioma, epithelial-myoepithelial carcinoma, and adenoid cystic carcinoma. Myoepithelial tumors can be differentiated from other primary salivary-type tumors of the lung based on the absence of a ductal component. Criteria to distinguish between myoepithelioma and myoepithelial carcinoma of the lung are not well established. Although there are no firm criteria for the diagnosis of malignancy in myoepithelial tumors of the salivary gland; invasion beyond the tumor capsule, cytologic atypia, and mitotic rate are reported to be helpful in establishing malignancy. In a study of 25 cases of myoepithelial carcinoma of the salivary glands, Savera and colleagues found that tumor infiltration into surrounding tissue is the most notable feature, and that the absence of cytologic atypia does not preclude the diagnosis of myoepithelial carcinoma. In fact, 60% of the cases were classified as low grade, with uniform small intermediatesized nuclei, finely dispersed chromatin, and inconspicuous nucleoli. In contrast, high-grade tumors showed enlarged nuclei, nuclear pleomorphism, chromatin www.appliedimmunohist.com |
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TABLE 3. Immunohistochemical Profiles of Reported Cases References Higashiyama et al4 Higashiyama et al4 Sekine et al5 Miura et al6 Masuya et al7 Tanahashi et al8 Sarkaria et al9 Hysi et al10 This study
S100 SMA Vimentin + NA + + + + NA
+ + NA NA + + + +
EMA
NA + + +
/+* NA + + +
NA
NA NA
Desmin CK AE1/AE3 CK8/18 GFAP Calponin CD99 SMMS CD10 p63
NA +
+ /+* NA + NA + +
+ NA
NA NA NA NA + NA NA NA +
NA NA + + NA
NA NA NA + NA NA F
NA NA NA NA NA NA + NA +
NA NA NA + NA NA NA NA F
NA NA NA NA NA NA NA +
NA NA NA NA NA + NA NA +
*Plasmacytoid cells negative for EMA and CK AE1/AE3, squamoid cells positive for both markers. F indicates focal; NA, not available.
clumping, prominent nucleoli, and nuclear membrane irregularities.13
CONCLUSIONS Primary myoepithelial carcinoma of the lung is a rare malignancy that shares histologic and immunohistochemical features with myoepithelial cell carcinoma of the salivary gland. On the basis of the reported cases, most patients are male, middle-aged to elderly, and of Asian ethnicity with a smoking history. The tumors are generally unifocal, endobronchial in location, and under 7 cm in size. On gross examination, myoepithelial carcinoma is white, solid, nodular, and well-defined. Cyst formation and necrosis may be observed. Myoepithelial carcinoma of the lung shows a varied and often biphasic morphology with spindle, plasmacytoid, clear, and epithelial cell types. Tumor stroma varies from myxoid to myxohyaline to hyalinized. Tumors have an elevated
mitotic index, and cytologic atypia and necrosis are not uncommonly present. All reported cases were positive for at least 1 myoepithelial cell marker and variably positive for keratins. The documented cases have all been managed surgically, with wedge resection, lobectomy, or pneumonectomy. The majority of patients developed metastatic disease, of sites including the lung, brain, liver, and soft tissue. The high rate of metastasis, high mitotic index, and occasional necrosis suggest that myoepithelial carcinoma of the lung has a high malignant potential. Although tumor infiltration is an important indicator for malignancy in myoepithelial tumors of the salivary glands, myoepithelial carcinomas of the lung are generally well circumscribed and the majority are noninfiltrative. Interestingly, patients with metastases have been observed to have a higher mitotic index than those with no metastatic disease.10 In the reviewed cases, tumors that developed metastases had an average mitotic rate of 18/10 HPF, whereas those without metastasis had an
FIGURE 2. Immunohistochemistry of myoepithelial carcinoma. The tumor is positive for CD10 (A), CK7 (B), CK5 (C), p63 (D), calponin (E), and SMA (F).
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average mitotic rate of 4.5/10 HPF. In addition, the 3 tumors with necrosis were all associated with metastatic disease.4,6,9 These findings suggest that mitotic activity and the presence of necrosis may be useful prognostic markers of myoepithelial cell carcinoma of the lung. REFERENCES 1. Colby TV, Koss MN, Travis WD. Tumors of salivary gland type. In: Colby TV, Koss MN, Travis WD, eds. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology; 1995:65–89. 2. Hornick JL, Fletcher CD. Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2003;27: 1183–1196. 3. Moran CA. Primary salivary gland-type tumors of the lung. Semin Diagn Pathol. 1995;12:106–122. 4. Higashiyama M, Kodama K, Yokouchi H, et al. Myoepithelioma of the lung: report of two cases and review of the literature. Lung Cancer. 1998;20:47–56. 5. Sekine I, Kodama T, Yokose T, et al. Rare pulmonary tumors—a review of 32 cases. Oncology. 1998;55:431–434.
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Myoepithelial Carcinoma of the Lung
6. Miura K, Harada H, Aiba S, et al. Myoepithelial carcinoma of the lung arising from bronchial submucosa. Am J Surg Pathol. 2000;24:1300–1304. 7. Masuya D, Haba R, Huang CL, et al. Myoepithelial carcinoma of the lung. Eur J Cardiothorac Surg. 2005;28:775–777. 8. Tanahashi J, Kashima K, Tsutomu D, et al. Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature. Acta Pathol Microbiol Immunol Scand. 2010;118:401–406. 9. Sarkaria IS, DeLair D, Travis WD, et al. Primary myoepithelial carcinoma of the lung: a rare entity treated with parenchymal sparing resection. J Cardiovasc Surg. 2011;6:27. 10. Hysi I, Wattez H, Benhamed L, et al. Primary pulmonary myoepithelial carcinoma. Interact Cardiovasc Thorac Surg. 2011;13: 226–228. 11. Ellis GL, Auclair PL. Malignant Epithelial Neoplasms: In AFIP Atlas of Tumor Pathology. Fourth Series Fasicle 9. Tumors of the Salivary Glands. Maryland: ARP Press; 2008:341–349. 12. Skalova A, Jakel KT. Myoepithelial carcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization Classification of Tumours. Pathology and Genetics Head and Neck Tumours. Lyon: IARC Press; 2005;240. 13. Savera AT, Sloman A, Huvos AG, et al. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol. 2000;24:761–774.
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401
Myoepithelial Carcinoma of the Lung: A Review Lauren E. Rosen, MD,* Rohit I. Singh, MD,* Michael Vercillo, MD,w and Paolo Gattuso, MD*
Abstract: Primary myoepithelial carcinoma of the lung is a rare neoplasm with only 8 cases reported in the English literature to date. Myoepithelial carcinomas of the lung are thought to arise from submucosal bronchial glands and have morphologic features similar to their salivary gland counterparts. The pathologic features and immunohistochemical profile of this tumor have not yet been summarized in the literature. Our objective is to review the clinicopathologic features and immunohistochemistry of these tumors. Key Words: myoepithelial carcinoma, immunohistochemistry, salivary-type lung tumors (Appl Immunohistochem Mol Morphol 2015;23:397–401)
P
rimary salivary-type tumors of the lung, including myoepithelial carcinoma, are rare. Myoepithelial carcinomas primarily occur in the salivary glands, parotid, and breast.1 Myoepithelial carcinomas arising in soft tissue have also been reported.2 Primary salivary glandtype tumors of the lung are thought to arise from submucosal bronchial glands in the lower respiratory tract and have morphologic features similar to those of their salivary gland counterparts.3 Myoepithelial tumors, including myoepithelioma and myoepithelial carcinoma show myoepithelial differentiation and lack a ductal component. The first case of myoepithelial carcinoma was described by Higashiyama et al in 1998 and to date, there are only 8 cases of myoepithelial carcinoma reported in the English literature.4–10
DISCUSSION The clinical features of the 8 reported cases and 1 case from our institution are summarized in Table 1. With the exception of 1 case in which little clinical information is available, patients ranged in age from 58 to 76 years with a mean age of 60 years. Five patients were male and 3 were female. Of the 7 cases where race was specified, 2 patients were white, 2 were Japanese, and 3 were described only as Asian.4,6–8,10 The majority of patients (71%) had a smoking history. Four tumors were uniReceived for publication March 24, 2014; accepted May 5, 2014. From the Departments of *Pathology; and wCardiovascular and Thoracic Surgery, Rush University Medical Center, Chicago, IL. The authors declare no conflict of interest. Reprints: Lauren E. Rosen, MD, Department of Pathology, Rush University Medical Center, 1750 W Congress Parkway, Suite 532, Chicago, IL 60612 (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
Appl Immunohistochem Mol Morphol
focal,4,5,7,8 one was described as a consisting of confluent multinodular tumor.6 Most tumors were endobronchial (4 of 7) and the remaining were peripherally located. Tumors ranged in size from 1.5 to 13 cm with a mean size of 4.3 cm. All patients underwent surgical resection by wedge resection, lobectomy, or pneumonectomy. Seven cases showed metastases, involving the lung, liver, brain, or soft tissue.4–6,8–10 One patient had a lung metastasis and diagnosis9 and 1 patient presented with 3 metastatic lung lesions 15 months following initial resection.10 Two patients with metastatic disease died of disease at 11 and 60 months postoperatively, respectively.4,8 One patient died of other causes at 14 months.4 Two patients were reported to be alive with disease at 7 and 36 months, respectively,6,9 and 3 patients were reported to be without evidence of disease at 3, 10, and 15 months postoperatively.7,10 The imaging features of myoepithelial carcinoma of the lung are not well described in the literature. Imaging studies were performed in 7 of the 8 reviewed cases.4–10 In all but 2 cases, both chest x-ray and chest computed tomography (CT) were performed.4–7,9,10 On chest x-ray, the lesion is described in all cases as a nodule or shadow. By chest CT, the tumor was described in 1 case as a smoothly circumscribed heterogenous mass,9 in a second as a solid spiculated mass,8 and in a third as a nodular shadow with irregular borders.7 In 1 patient with metastatic lung lesions, CT demonstrated well-circumscribed nodules.10 Two lesions were not further characterized by CT.4,6 Two lung lesions, 1 primary and 1 metastatic were hypermetabolic by positron emission tomography.7,10 The patient from our institution was found to have a nodule on chest x-ray, and a subsequent chest CT showed a spiculated mass. The lesion was hypermetabolic by positron emission tomography with a standard uptake value of 6.6. Pathologic features, available in 8 cases including 1 case from our institution, are summarized in Table 2. Gross findings are available in 5 cases. The majority of tumors are described as well-circumscribed and nodular with a solid white cut surface. One case showed gross necrosis and cyst formation.6 The histology varied among cases. The majority of tumors were biphasic; composed of epithelioid, plasmacytoid, squamoid, spindle, and or clear cells. The stroma was described in only 2 cases, as myxoid in both.7–8 Our case showed cords and nests of oval to fusiform clear cells with small single nucleoli and minimal atypia arranged around a central hyalinized matrix (Fig. 1). Tanahashi et al8 described a case with similar morphology, composed of a central area containing
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Volume 23, Number 6, July 2015
TABLE 1. Clinical Description of Reported Cases Age/ Sex
Race
Smoking History
Higashiyama et al4 Higashiyama et al4 Sekine et al5 Miura et al6
58/M
Japanese
Yes
RUL, endobronchial
58/M
Japanese
Yes
LUL, endobronchial
NA 46/M
NA Asian
NA NA
Masuya et al7
48/M
Asian
Yes
NA Right mainstem bronchus LLL, endobronchial
LLL lobectomy
15
Tanahashi et al8 Sarkaria et al9
76/M
Asian
Yes
LLL, peripheral
LLL wedge resection
22
63/F
NA
No
60/F
White
No
RLL wedge resection, excision LLL wedge resection
130
Hysi et al10
RLL, peripheral and pleural LLL, peripheral
This study
72/F
White
Yes
RUL, endobronchial
RUL wedge resection
15
References
Location
Tumor Size (mm)
Surgery Sleeve bilobectomy (RUL, RML) LUL sleeve lobectomy
38 60
NA Right pneumonectomy
NA 65
25
Metastases
Outcome
Soft tissue left arm DOC, 14 mo Liver DOD, 60 mo Yes NA LLL NED, 7 mo AWD, 7 mo No NED, 15 mo Brain DOD, 11 mo RLL (pleura) and AWD, liver 36 mo LLL and RLL NED, 10 mo No NED, 7 mo
AWD indicates alive with disease; DOC, dead of other cause; DOD, dead of disease; HPF, high-power field; LLL, left lower lobe; LUL, left upper lobe; NA, not available; NED, no evidence of disease; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe.
eosinophilic polygonal and clear cells arranged in a cordlike and reticular pattern within an abundant myxohyaline stroma. The periphery of this lesion, in contrast to our case, was hypercellular and composed of solid lobules of atypical cells with a high mitotic index and focal comedonecrosis. One case was composed of spindle cells (based only on the published photograph) and the other describes only the presence of a fibrous capsule.6,9 Two endobronchial tumors showed invasion into the bronchial mucosa with associated bronchial ulceration.4,6 Cyst formation was reported in 2 tumors, both of which were composed of spindle and plasmacytoid cells.1,6 Necrosis
was described in 3 cases,4,6,9 and the mitotic index ranged from 4 to 32/10 HPF (mean 13/10 HPF).6–8,10 The immunohistochemical profile of myoepithelial carcinoma of the lung has yet to be established. Normal myoepithelial cells express CK14, SMA, MSA, calponin, SMMS, and p63.11 The diagnosis of salivary gland myoepithelial carcinoma requires reactivity for cytokeratin and at least one other myoepithelial cell marker, including calponin, CD10, GFAP, SMA, or SMMS.12 SMA, calponin, SMMS, and GFAP are specifically but inconsistently expressed by salivary gland tumors with myoepithelial differentiation. S100, p63, and vimentin are
TABLE 2. Pathologic Features of Reported Cases References
Gross Appearance
Cell Type
Other Histologic Features
Higashiyama et al4
NA
Biphasic, spindle, and plasmacytoid cells
Higashiyama et al4 Miura et al6
NA
Biphasic, squamoid, and plasmacytoid cells Biphasic, spindle, and plasmacytoid cells
Masuya et al7
White, solid, multinodular with focal necrosis, and cyst formation NA
Tanahashi et al8 Well circumscribed, white, multilobulated, solid
Sarkaria et al9 Hysi et al10 This study
Well circumscribed, nodular Well-circumscribed, nodular White, solid, well-circumscribed
Interspersed microcystic areas, necrosis, hemorrhage. Open chromatin, indistinct nuclear membranes, inconspicuous nucleoli Plasmacytoid cells with eosinophilic cytoplasm
Spindled (based on published photograph)
Oval nuclei, focal macronuclei and multinucleated tumor cells, myxoid stroma Biphasic, epithelioid, and clear cells Central hyaline myxocellular area with cords of cells and peripheral hypercellular area with solid lobules of atypical cells and focal necrosis Fibrous capsule, necrosis (20%) Biphasic, spindle cells, and clear cells Minimal atypia, oval nuclei Oval to fusiform clear cells Minimal atypia, prominent nucleoli, hyalinized stroma
Mitoses/ 10 HPFs Sporadic
Numerous 13 5 32
NA 9 4
NA indicates not available.
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Myoepithelial Carcinoma of the Lung
FIGURE 1. Myoepithelial carcinoma. A, Radiating cords and nests of tumor cells surrounding a centrally hyalinized matrix. B, Radiating cords of fusiform tumor cells. C and D, The tumor cells are oval to fusiform with round to oval nuclei, fine vesicular chromatin, small nucleoli, and clear cytoplasm. The tumor was endobronchial.
sensitive but nonspecific markers. Cytokeratins are variably expressed by myoepithelial carcinomas of the salivary gland, with AE1/AE3 being the most sensitive. The tumors are typically negative for CK7, CEA, CD117, and desmin and have been reported to show weak EMA positivity.11,13 The immunoprofile of the reported cases of myoepithelial cell carcinoma of the lung, including our case, is summarized in Table 3. Of the 9 cases reviewed, keratin positivity was present in 6 of 8, or 75% of cases; 5 of 6 for AE1/AE3 and 2 of 2 for CK8/18 (Fig. 2). Tumor cells were positive for SMA (6 of 7), S100 (5 of 7), SMMS (2 of 2), p63 (2 of 2), and CD99 (2 of 2). Less frequent positivity was reported with EMA (3 of 6), calponin (2 of 4), CD10 (1 of 2), vimentin (4 of 7), GFAP (2 of 6), and desmin (2 of 8). Three cases describe the tumor cells as PAS positive and PAS-D negative.4,8 Tumor cells with squamoid differentiation; preset focally in 1 case; were positive for EMA, AE1/AE3, and CEA.4 In one of the 2 cases in which myxoid stroma was described, the stroma was positive for Alcian blue pH 2.5 and metachromatic with toluene blue.8 Copyright
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2014 Wolters Kluwer Health, Inc. All rights reserved.
The differential diagnosis of myoepithelial carcinoma is broad and includes other salivary-type tumors such as myoepithelioma, epithelial-myoepithelial carcinoma, and adenoid cystic carcinoma. Myoepithelial tumors can be differentiated from other primary salivary-type tumors of the lung based on the absence of a ductal component. Criteria to distinguish between myoepithelioma and myoepithelial carcinoma of the lung are not well established. Although there are no firm criteria for the diagnosis of malignancy in myoepithelial tumors of the salivary gland; invasion beyond the tumor capsule, cytologic atypia, and mitotic rate are reported to be helpful in establishing malignancy. In a study of 25 cases of myoepithelial carcinoma of the salivary glands, Savera and colleagues found that tumor infiltration into surrounding tissue is the most notable feature, and that the absence of cytologic atypia does not preclude the diagnosis of myoepithelial carcinoma. In fact, 60% of the cases were classified as low grade, with uniform small intermediatesized nuclei, finely dispersed chromatin, and inconspicuous nucleoli. In contrast, high-grade tumors showed enlarged nuclei, nuclear pleomorphism, chromatin www.appliedimmunohist.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
399
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Rosen et al
Volume 23, Number 6, July 2015
TABLE 3. Immunohistochemical Profiles of Reported Cases References Higashiyama et al4 Higashiyama et al4 Sekine et al5 Miura et al6 Masuya et al7 Tanahashi et al8 Sarkaria et al9 Hysi et al10 This study
S100 SMA Vimentin + NA + + + + NA
+ + NA NA + + + +
EMA
NA + + +
/+* NA + + +
NA
NA NA
Desmin CK AE1/AE3 CK8/18 GFAP Calponin CD99 SMMS CD10 p63
NA +
+ /+* NA + NA + +
+ NA
NA NA NA NA + NA NA NA +
NA NA + + NA
NA NA NA + NA NA F
NA NA NA NA NA NA + NA +
NA NA NA + NA NA NA NA F
NA NA NA NA NA NA NA +
NA NA NA NA NA + NA NA +
*Plasmacytoid cells negative for EMA and CK AE1/AE3, squamoid cells positive for both markers. F indicates focal; NA, not available.
clumping, prominent nucleoli, and nuclear membrane irregularities.13
CONCLUSIONS Primary myoepithelial carcinoma of the lung is a rare malignancy that shares histologic and immunohistochemical features with myoepithelial cell carcinoma of the salivary gland. On the basis of the reported cases, most patients are male, middle-aged to elderly, and of Asian ethnicity with a smoking history. The tumors are generally unifocal, endobronchial in location, and under 7 cm in size. On gross examination, myoepithelial carcinoma is white, solid, nodular, and well-defined. Cyst formation and necrosis may be observed. Myoepithelial carcinoma of the lung shows a varied and often biphasic morphology with spindle, plasmacytoid, clear, and epithelial cell types. Tumor stroma varies from myxoid to myxohyaline to hyalinized. Tumors have an elevated
mitotic index, and cytologic atypia and necrosis are not uncommonly present. All reported cases were positive for at least 1 myoepithelial cell marker and variably positive for keratins. The documented cases have all been managed surgically, with wedge resection, lobectomy, or pneumonectomy. The majority of patients developed metastatic disease, of sites including the lung, brain, liver, and soft tissue. The high rate of metastasis, high mitotic index, and occasional necrosis suggest that myoepithelial carcinoma of the lung has a high malignant potential. Although tumor infiltration is an important indicator for malignancy in myoepithelial tumors of the salivary glands, myoepithelial carcinomas of the lung are generally well circumscribed and the majority are noninfiltrative. Interestingly, patients with metastases have been observed to have a higher mitotic index than those with no metastatic disease.10 In the reviewed cases, tumors that developed metastases had an average mitotic rate of 18/10 HPF, whereas those without metastasis had an
FIGURE 2. Immunohistochemistry of myoepithelial carcinoma. The tumor is positive for CD10 (A), CK7 (B), CK5 (C), p63 (D), calponin (E), and SMA (F).
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average mitotic rate of 4.5/10 HPF. In addition, the 3 tumors with necrosis were all associated with metastatic disease.4,6,9 These findings suggest that mitotic activity and the presence of necrosis may be useful prognostic markers of myoepithelial cell carcinoma of the lung. REFERENCES 1. Colby TV, Koss MN, Travis WD. Tumors of salivary gland type. In: Colby TV, Koss MN, Travis WD, eds. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology; 1995:65–89. 2. Hornick JL, Fletcher CD. Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2003;27: 1183–1196. 3. Moran CA. Primary salivary gland-type tumors of the lung. Semin Diagn Pathol. 1995;12:106–122. 4. Higashiyama M, Kodama K, Yokouchi H, et al. Myoepithelioma of the lung: report of two cases and review of the literature. Lung Cancer. 1998;20:47–56. 5. Sekine I, Kodama T, Yokose T, et al. Rare pulmonary tumors—a review of 32 cases. Oncology. 1998;55:431–434.
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Myoepithelial Carcinoma of the Lung
6. Miura K, Harada H, Aiba S, et al. Myoepithelial carcinoma of the lung arising from bronchial submucosa. Am J Surg Pathol. 2000;24:1300–1304. 7. Masuya D, Haba R, Huang CL, et al. Myoepithelial carcinoma of the lung. Eur J Cardiothorac Surg. 2005;28:775–777. 8. Tanahashi J, Kashima K, Tsutomu D, et al. Pulmonary myoepithelial carcinoma resembling matrix-producing carcinoma of the breast: case report and review of the literature. Acta Pathol Microbiol Immunol Scand. 2010;118:401–406. 9. Sarkaria IS, DeLair D, Travis WD, et al. Primary myoepithelial carcinoma of the lung: a rare entity treated with parenchymal sparing resection. J Cardiovasc Surg. 2011;6:27. 10. Hysi I, Wattez H, Benhamed L, et al. Primary pulmonary myoepithelial carcinoma. Interact Cardiovasc Thorac Surg. 2011;13: 226–228. 11. Ellis GL, Auclair PL. Malignant Epithelial Neoplasms: In AFIP Atlas of Tumor Pathology. Fourth Series Fasicle 9. Tumors of the Salivary Glands. Maryland: ARP Press; 2008:341–349. 12. Skalova A, Jakel KT. Myoepithelial carcinoma. In: Barnes L, Eveson JW, Reichart P, Sidransky D, eds. World Health Organization Classification of Tumours. Pathology and Genetics Head and Neck Tumours. Lyon: IARC Press; 2005;240. 13. Savera AT, Sloman A, Huvos AG, et al. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol. 2000;24:761–774.
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