- Email: [email protected]
Glycogen-rich clear cell mammary malignant myoepithelioma
ARTICLE IN PRESS The Breast (2004) 13, 506–509
THE
BREAST www.elsevier.com/locate/breast
Case report
Glycogen-rich clear cell mammary malignant myoepithelioma Hyun Jin Sona, Sung Hoo Jungb, Sang Yong Leec, Woo Sung Moona, a
Department of Pathology, Chonbuk National University Medical School, and Institute for Medical Science, San 2-20, Keumam-Dong, Dukjin-gu, Jeonju, Jeollabuk-do 561-180, Republic of Korea b Department of Surgery, Chonbuk National University Medical School, and Institute for Medical Science, Republic of Korea c Department of Radiology, Chonbuk National University Medical School, and Institute for Medical Science, Republic of Korea Received 16 February 2004; received in revised form 12 May 2004; accepted 7 July 2004
KEYWORDS Breast; Glycogen; Malignant myoepithelioma; Immunohistochemistry
Summary Primary clear cell tumors of the breast are uncommon and often present a diagnostic challenge. We describe an extremely rare case of glycogen-rich clear cell malignant myoepithelioma in a 43-year-old woman. Histologically, this tumor is composed of clear cells with abundant cytoplasmic glycogen particles. Immunohistochemically, these tumor cells show co-expression of vimentin, smooth muscle actin, epithelial membrane antigen, S-100 protein, and cytokeratin as evidence of myoepithelial cell tumor. The pathological staging of the patient is IIB (pT3N0M0) and the nuclear grading is 2. The patient demonstrated no evidence of recurrence or metastasis over a period of 42 months. We suggest that glycogen-rich clear cell malignant myoepithelioma be included in the histological differential diagnosis of clear cell tumors of the breast. r 2004 Elsevier Ltd. All rights reserved.
Introduction Primary clear cell tumors of the breast are relatively rare neoplasms. The differential diagnoses include lipid-rich,1 glycogen-rich,2 secretory,3 and signet ring cell carcinoma.4 In myoepithelial tumors the cells are elongated and have eosinophilic cytoplasm, Corresponding author. Tel.: +82-63-270-3086; fax.: +82-63-
270-3135. E-mail address: [email protected] (W.S. Moon).
giving the appearance of leiomyoma-like or spindle cell tumors.5 Cartagena et al.6 were the first to describe clear cell mammary malignant myoepithelioma. It is not known why myoepithelial cells exhibit clear cytoplasm under the light microscope. As far as we know, only three cases of tumors composed of clear malignant myoepithelial cells with abundant glycogen have been reported hitherto.7,8 In this paper, we report a similar case of a tumor with abundant glycogen and immunohistochemical features of myoepithelial differentiation.
0960-9776/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2004.07.003
ARTICLE IN PRESS Glycogen-rich clear cell mammary malignant myoepithelioma
507
Case report A 43-year-old woman presented with a painful, hard, and circumscribed mass measuring 8 8 cm2 in the upper part of the right breast. The mass had first been detected 8 months before and was growing rapidly. Movable, enlarged lymph nodes were palpated in the ipsilateral axilla. The mass was too large for a film mammography to be possible. On ultrasound examination the central portion of the mass was seen as a fluid density owing to necrosis. The solid portion of the mass demonstrated heterogeneous echogenicity with a well-defined margin. A fine-needle aspiration biopsy was performed and yielded necrotic tissue and evidence of acute suppurative inflammation. An incisional biopsy was subsequently performed, revealing histological features consistent with a malignant clear cell tumor. There was no evidence of distant metastasis, and the clinical staging was IIIA (T3N1M0). After a chemotherapy composed of four cycles of cyclophosphamide, Adriamycin, 5FU and one cycle of Taxols (paclitaxel), a modified radical mastectomy including a skin allograft was performed. When the patient visited for her third chemotherapy session the mass measured 7 6.5 cm2. The mastectomy specimen contained a well-circumscribed, firm, yellowish tan mass 6 6 cm2 in size and no metastatic lesions in a total of 34 lymph nodes in the axillary contents (pT3N0M0). Histologically, the tumor was characterized by the proliferation of cells in a generally solid or a cord formation and showed an infiltrative growth pattern. The individual tumor cells revealed optically clear cytoplasm and contained centrally located vesicular nuclei with prominent nucleoli (Fig. 1A,B). The nuclear grade was 2 according to the Bloom and Richardson grading system.9 Occasional spindle cells with acidophilic cytoplasm were also observed. Degeneration and shrinkage of tumor cells, retraction of tumor cells from the intervening stroma, edematous and degenerative changes of the stroma, and atypical changes of the stromal cells were recognized, and these features were not seen in the incisional biopsy, or only to a lesser degree. There were 10–13 mitoses per 10 high-power fields. In the periodic acid-Schiff (PAS)stained preparations the tumor cells showed abundant fine positive granules in the cytoplasm (Fig. 1C), and most of them were digested with diastase (Fig. 1D). Mucicarmine, Oil Red O, and Grimelius stainings were completely negative. Immunostaining showed strongly positive reactions for vimentin (DAKO, Glostrup, Denmark), smooth muscle actin (SMA; DAKO, Glostrup, Denmark), and epithelial membrane antigen (EMA; DAKO,
Figure 1 (A,B) Tumor cells with optically clear cytoplasm and vesicular nuclei with prominent nucleoli (H&E, 200); (C) tumor cells containing strongly PAS-positive cytoplasmic materials (PAS, 200); (D) most of these were digested with diastase, and the cells showed clear cytoplasm (DPAS, 200); (E) a positive reaction for EMA (ABC, 200); (F) a strongly positive reaction for vimentin in clear tumor cells; (G) weak nuclear and cytoplasmic positive reactions for S-100 protein; and (H) positive reaction for SMA. The blood vessel wall (bottom left) was also positive for SMA.
Glostrup, Denmark) in most of the tumor cells. S-100 protein (DAKO, Glostrup, Denmark) showed positive reactions in the cytoplasm and nucleus of the tumor cells. Cytokeratin (CK; DAKO, Glostrup, Denmark) was focally positive, but the other antibodies, including the estrogen receptor (DAKO, Carpinteria, CA), progesterone receptor (DAKO, Carpinteria, CA), C-erbB2 (DAKO, Carpinteria, CA), neuron-specific enolase (DAKO, Glostrup, Denmark), chromogranin (DAKO, Glostrup, Denmark), carcinoembryonic antigen (DAKO, Glostrup, Denmark), and alpha lactalbumin (DAKO, Carpinteria, CA) were negative (Fig. 1E–H). The material for the ultrastructural study was obtained from paraffin
ARTICLE IN PRESS 508
H.J. Son et al.
blocks. Though the tissue was too poorly preserved for detailed examination of its cellular morphology, abundant cytoplasmic glycogen, a few microfilaments and intercellular junctions were identifiable. The patient received two cycles of Taxols (paclitaxel) chemotherapy after radical mastectomy and underwent autologous peripheral blood stem cell transplantation for high-dose chemotherapy. Postoperatively, the patient demonstrated no evidence of recurrence or metastasis over a follow-up period of 42 months.
Discussion Myoepithelial lesions of the breast can be divided into three categories: myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma.10 Malignant myoepithelioma is an extremely rare tumor.6–8,10–12 The myoepithelial cells sometimes have abundant clear cytoplasm, although it is not specific to this type of cells.13 Whether this is the result of a processing artifact or of the cytoplasmic content of these cells has not been satisfactorily explained. Among the reported cases of malignant myoepithelioma, only five have been described as clear cell mammary malignant myoepithelioma Table 1
(Table 1).6–8,11 Tamai14 described two characteristics that could allow the identification of myoepithelial features in the breast neoplastic cells of intraductal carcinoma. First, the peripheral presence of clear zones within the involved ducts, which occurred rather more regularly than in other types of intraductal carcinoma and were occasionally found in a narrow band differing from the configuration in the classic type of intraductal carcinoma, in which there are sometimes cells with clear or pale cytoplasm but these are not arranged in a regular pattern. Secondly, there was a transition from clear cells to non-clear polygonal cells, and then to spindle cells. Although our patient had an invasive carcinoma, we observed spindle cells with eosinophilic cytoplasm in proximity to the cells with optically clear cytoplasm. Moreover, PAS staining with diastase digestion revealed the presence of abundant glycogen in the cytoplasm of the clear cells. The clear myoepithelial cells can contain glycogen in breast myoepithelial cell tumors7,8,10,11,14 or in salivary gland tumors.15 Previously reported cases and our case reveal that the accumulation of glycogen is responsible in part for the transformation of tumor cells in malignant myoepithelioma to clear cells.7,8,10,14
Literature review of clear cell mammary malignant myoepithelioma.
Authors (year of publication)
Age/sex of patient/s
Location of lesion
Cytoplasmic glycogens
ER/PR status of tumor
Tumor size/ pathologic staging
Treatment/ follow-up
Cartagena et al.6 (1988) Soares et al.7 (1994)
77/F
L, U
A few
470/245*
Excision/-
42/F
L, UOQ
Abundant
—
47/F
R, UOQ
Abundant
—
Kuwabara et al.8 (1997)
46/F
R
Abundant
Negative/ negative
3.5 1.2 cm/ T2NX In situ lesion; 1.5 cm/T1c In situ+ invasive lesion; 0.8 cm/T1bN0 2.3 1.0 cm/ T2N0
Miura et al.11 (2003) Present case
30/F
L, ESR
A few
43/F
R, U
Abundant
Weakly positive (IHC) Negative/ negative (IHC)
2.3 1.3 cm/ T2 6 6 cm/IIB (T3N0M0)
Q with ALND/no Recurrence at 12 and 4 months Partial mastectomy with ALND/no recurrence or metastasis at 7 months Q/Neoadjuvant chemotherapy+ MRM with ALND/no recurrence or metastasis at 42 months
R, right; L, left; U, upper part; UOQ, upper outer quadrant; ESR, external superior area; ER, estrogen receptor; PR, progesterone receptor; *Positive value410 fmol/mg; IHC, immunohistochemistry; Q, quadrantectomy; ALND, axillary lymph node dissection; MRM, modified radical mastectomy.
ARTICLE IN PRESS Glycogen-rich clear cell mammary malignant myoepithelioma The differential diagnoses in the case of clear cell malignant myoepithelioma include glycogen-rich,2 lipid-rich,1 secretory,3 and signet ring cell carcinoma,4 clear cell variant of apocrine and argyrophilic carcinoma, and adenoid cystic carcinoma with sebaceous differentiation. The clear cells of these tumors, except for glycogen-rich carcinoma, are easily differentiated from those of myoepithelial carcinoma with special stains that identify glycogen, fat, mucin, and neurosecretory granules. Cytoplasmic vacuolization and clearing are features associated with atypical apocrine proliferations, and they are usually most prominent in apocrine carcinoma. The tumor cells of apocrine carcinoma contain diastase-resistant PAS-positive granules, and they tend to be positive for CEA and usually negative for S-100 protein. In contrast to apocrine carcinoma, the tumor cells of our patient showed diastase-labile PAS-positive granules, which were negative for CEA and positive for S-100 protein. Sebaceous neoplasms show positive for fat. However, in our case the tumor cells were negative on fat staining. No positive Grimelius reaction, positivity for NSE and chromogranin, or neurosecretory granules, which have been seen in endocrine mammary carcinoma, were found. The antibodies most commonly used for the identification of myoepithelial cells were CK, vimentin, SMA, S-100 proteins, and glial fibrillary acidic proteins. These antibodies are not specific for myoepithelial cells, but when applied together positive findings indicate myoepithelial differentiation with a reasonable degree of confidence. Moreover, cells of glycogen-rich carcinoma will not react with SMA. In the present case, tumor cells in the lesions showed a highly specific myoepithelial phenotype: co-expression of CK, EMA, SMA, S-100 protein, and vimentin in the same cells. Therefore, the tumor in the present case must have been of myoepithelial origin, or at least be myoepithelial in nature. The biological behavior of this type of tumor and the prognosis of the patient are not known because so few cases have been documented in the literature. It is essential to be able to recognize
509
clear cell malignant myoepithelioma, so that we can learn more about their natural history and how they respond to treatment.
References 1. Ramos CV, Taylor HB. Lipid-rich carcinoma of the breast: a clinicopathologic analysis of 13 examples. Cancer 1974; 33:812–9. 2. Hayes MMM, Seidman JD, Ashton MA. Glycogen-rich clear cell carcinoma of the breast: a clinicopathologic study of 21 cases. Am J Surg Pathol 1995. 3. Oberman HA. Secretory carcinoma of the breast in adults. Am J Surg Pathol 1980;4:465–70. 4. Merino MJ, Livolsi VA. Signet ring cell carcinoma of the female breast: a clinicopathologic analysis of 14 cases. Cancer 1981;48:1830–7. 5. Al-Nafussi A. Spindle cell tumors of the breast: practical approach to diagnosis. Histopathology 1999;35:1–13. 6. Cartagena Jr N, Cabello-Inchausti B, Willis I, Poppiti Jr. R. Clear cell myoepithelial neoplasm of the breast. Hum Pathol 1988;19:1239–43. 7. Soares J, Tomasic G, Bucciarelli E, Eusebi V. Intralobular growth of myoepithelial cell carcinoma of the breast. Virchows Arch 1994;425:205–10. 8. Kuwabara H, Uda H. Clear cell mammary malignant myoepithelioma with abundant glycogens. J Clin Pathol 1997;50:700–2. 9. Bloom HJG, Richardson WW. Histologic grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957;11: 359–77. 10. Tavassoli FA. Myoepithelial lesions of the breast: myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma. Am J Surg Pathol 1991;15:554–68. 11. Miura Y, Kurose A, Kondo M, Maruyama A, Shibata Y, Kanno H, Sawai T. Clear cell myoepithelial carcinoma of the breast: a case report. Tohoku J Exp Med 2003;200:103–9. 12. Torner PS, Kahn HJ, Baumal R, Lee K, Moffat W. Malignant myoepithelioma of the breast. An immunohistochemical study by light and electron microscopy. Cancer 1986;57: 745–50. 13. Hamperl H. The myoepithelia (myoepithelial cells). Normal state; regressive change; hyperplasia; tumors. Curr Top Pathol 1970;53:161–220. 14. Tamai M. Intraductal growth of malignant mammary myoepithelioma. Am J Surg Pathol 1992;16:1116–25. 15. Saksela E, Tarkkanen J, Wartiovaara J. Parotid clear-cell adenoma of possible myoepithelial origin. Cancer 1972;30: 742–8.
THE
BREAST www.elsevier.com/locate/breast
Case report
Glycogen-rich clear cell mammary malignant myoepithelioma Hyun Jin Sona, Sung Hoo Jungb, Sang Yong Leec, Woo Sung Moona, a
Department of Pathology, Chonbuk National University Medical School, and Institute for Medical Science, San 2-20, Keumam-Dong, Dukjin-gu, Jeonju, Jeollabuk-do 561-180, Republic of Korea b Department of Surgery, Chonbuk National University Medical School, and Institute for Medical Science, Republic of Korea c Department of Radiology, Chonbuk National University Medical School, and Institute for Medical Science, Republic of Korea Received 16 February 2004; received in revised form 12 May 2004; accepted 7 July 2004
KEYWORDS Breast; Glycogen; Malignant myoepithelioma; Immunohistochemistry
Summary Primary clear cell tumors of the breast are uncommon and often present a diagnostic challenge. We describe an extremely rare case of glycogen-rich clear cell malignant myoepithelioma in a 43-year-old woman. Histologically, this tumor is composed of clear cells with abundant cytoplasmic glycogen particles. Immunohistochemically, these tumor cells show co-expression of vimentin, smooth muscle actin, epithelial membrane antigen, S-100 protein, and cytokeratin as evidence of myoepithelial cell tumor. The pathological staging of the patient is IIB (pT3N0M0) and the nuclear grading is 2. The patient demonstrated no evidence of recurrence or metastasis over a period of 42 months. We suggest that glycogen-rich clear cell malignant myoepithelioma be included in the histological differential diagnosis of clear cell tumors of the breast. r 2004 Elsevier Ltd. All rights reserved.
Introduction Primary clear cell tumors of the breast are relatively rare neoplasms. The differential diagnoses include lipid-rich,1 glycogen-rich,2 secretory,3 and signet ring cell carcinoma.4 In myoepithelial tumors the cells are elongated and have eosinophilic cytoplasm, Corresponding author. Tel.: +82-63-270-3086; fax.: +82-63-
270-3135. E-mail address: [email protected] (W.S. Moon).
giving the appearance of leiomyoma-like or spindle cell tumors.5 Cartagena et al.6 were the first to describe clear cell mammary malignant myoepithelioma. It is not known why myoepithelial cells exhibit clear cytoplasm under the light microscope. As far as we know, only three cases of tumors composed of clear malignant myoepithelial cells with abundant glycogen have been reported hitherto.7,8 In this paper, we report a similar case of a tumor with abundant glycogen and immunohistochemical features of myoepithelial differentiation.
0960-9776/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2004.07.003
ARTICLE IN PRESS Glycogen-rich clear cell mammary malignant myoepithelioma
507
Case report A 43-year-old woman presented with a painful, hard, and circumscribed mass measuring 8 8 cm2 in the upper part of the right breast. The mass had first been detected 8 months before and was growing rapidly. Movable, enlarged lymph nodes were palpated in the ipsilateral axilla. The mass was too large for a film mammography to be possible. On ultrasound examination the central portion of the mass was seen as a fluid density owing to necrosis. The solid portion of the mass demonstrated heterogeneous echogenicity with a well-defined margin. A fine-needle aspiration biopsy was performed and yielded necrotic tissue and evidence of acute suppurative inflammation. An incisional biopsy was subsequently performed, revealing histological features consistent with a malignant clear cell tumor. There was no evidence of distant metastasis, and the clinical staging was IIIA (T3N1M0). After a chemotherapy composed of four cycles of cyclophosphamide, Adriamycin, 5FU and one cycle of Taxols (paclitaxel), a modified radical mastectomy including a skin allograft was performed. When the patient visited for her third chemotherapy session the mass measured 7 6.5 cm2. The mastectomy specimen contained a well-circumscribed, firm, yellowish tan mass 6 6 cm2 in size and no metastatic lesions in a total of 34 lymph nodes in the axillary contents (pT3N0M0). Histologically, the tumor was characterized by the proliferation of cells in a generally solid or a cord formation and showed an infiltrative growth pattern. The individual tumor cells revealed optically clear cytoplasm and contained centrally located vesicular nuclei with prominent nucleoli (Fig. 1A,B). The nuclear grade was 2 according to the Bloom and Richardson grading system.9 Occasional spindle cells with acidophilic cytoplasm were also observed. Degeneration and shrinkage of tumor cells, retraction of tumor cells from the intervening stroma, edematous and degenerative changes of the stroma, and atypical changes of the stromal cells were recognized, and these features were not seen in the incisional biopsy, or only to a lesser degree. There were 10–13 mitoses per 10 high-power fields. In the periodic acid-Schiff (PAS)stained preparations the tumor cells showed abundant fine positive granules in the cytoplasm (Fig. 1C), and most of them were digested with diastase (Fig. 1D). Mucicarmine, Oil Red O, and Grimelius stainings were completely negative. Immunostaining showed strongly positive reactions for vimentin (DAKO, Glostrup, Denmark), smooth muscle actin (SMA; DAKO, Glostrup, Denmark), and epithelial membrane antigen (EMA; DAKO,
Figure 1 (A,B) Tumor cells with optically clear cytoplasm and vesicular nuclei with prominent nucleoli (H&E, 200); (C) tumor cells containing strongly PAS-positive cytoplasmic materials (PAS, 200); (D) most of these were digested with diastase, and the cells showed clear cytoplasm (DPAS, 200); (E) a positive reaction for EMA (ABC, 200); (F) a strongly positive reaction for vimentin in clear tumor cells; (G) weak nuclear and cytoplasmic positive reactions for S-100 protein; and (H) positive reaction for SMA. The blood vessel wall (bottom left) was also positive for SMA.
Glostrup, Denmark) in most of the tumor cells. S-100 protein (DAKO, Glostrup, Denmark) showed positive reactions in the cytoplasm and nucleus of the tumor cells. Cytokeratin (CK; DAKO, Glostrup, Denmark) was focally positive, but the other antibodies, including the estrogen receptor (DAKO, Carpinteria, CA), progesterone receptor (DAKO, Carpinteria, CA), C-erbB2 (DAKO, Carpinteria, CA), neuron-specific enolase (DAKO, Glostrup, Denmark), chromogranin (DAKO, Glostrup, Denmark), carcinoembryonic antigen (DAKO, Glostrup, Denmark), and alpha lactalbumin (DAKO, Carpinteria, CA) were negative (Fig. 1E–H). The material for the ultrastructural study was obtained from paraffin
ARTICLE IN PRESS 508
H.J. Son et al.
blocks. Though the tissue was too poorly preserved for detailed examination of its cellular morphology, abundant cytoplasmic glycogen, a few microfilaments and intercellular junctions were identifiable. The patient received two cycles of Taxols (paclitaxel) chemotherapy after radical mastectomy and underwent autologous peripheral blood stem cell transplantation for high-dose chemotherapy. Postoperatively, the patient demonstrated no evidence of recurrence or metastasis over a follow-up period of 42 months.
Discussion Myoepithelial lesions of the breast can be divided into three categories: myoepitheliosis, adenomyoepithelioma, and malignant myoepithelioma.10 Malignant myoepithelioma is an extremely rare tumor.6–8,10–12 The myoepithelial cells sometimes have abundant clear cytoplasm, although it is not specific to this type of cells.13 Whether this is the result of a processing artifact or of the cytoplasmic content of these cells has not been satisfactorily explained. Among the reported cases of malignant myoepithelioma, only five have been described as clear cell mammary malignant myoepithelioma Table 1
(Table 1).6–8,11 Tamai14 described two characteristics that could allow the identification of myoepithelial features in the breast neoplastic cells of intraductal carcinoma. First, the peripheral presence of clear zones within the involved ducts, which occurred rather more regularly than in other types of intraductal carcinoma and were occasionally found in a narrow band differing from the configuration in the classic type of intraductal carcinoma, in which there are sometimes cells with clear or pale cytoplasm but these are not arranged in a regular pattern. Secondly, there was a transition from clear cells to non-clear polygonal cells, and then to spindle cells. Although our patient had an invasive carcinoma, we observed spindle cells with eosinophilic cytoplasm in proximity to the cells with optically clear cytoplasm. Moreover, PAS staining with diastase digestion revealed the presence of abundant glycogen in the cytoplasm of the clear cells. The clear myoepithelial cells can contain glycogen in breast myoepithelial cell tumors7,8,10,11,14 or in salivary gland tumors.15 Previously reported cases and our case reveal that the accumulation of glycogen is responsible in part for the transformation of tumor cells in malignant myoepithelioma to clear cells.7,8,10,14
Literature review of clear cell mammary malignant myoepithelioma.
Authors (year of publication)
Age/sex of patient/s
Location of lesion
Cytoplasmic glycogens
ER/PR status of tumor
Tumor size/ pathologic staging
Treatment/ follow-up
Cartagena et al.6 (1988) Soares et al.7 (1994)
77/F
L, U
A few
470/245*
Excision/-
42/F
L, UOQ
Abundant
—
47/F
R, UOQ
Abundant
—
Kuwabara et al.8 (1997)
46/F
R
Abundant
Negative/ negative
3.5 1.2 cm/ T2NX In situ lesion; 1.5 cm/T1c In situ+ invasive lesion; 0.8 cm/T1bN0 2.3 1.0 cm/ T2N0
Miura et al.11 (2003) Present case
30/F
L, ESR
A few
43/F
R, U
Abundant
Weakly positive (IHC) Negative/ negative (IHC)
2.3 1.3 cm/ T2 6 6 cm/IIB (T3N0M0)
Q with ALND/no Recurrence at 12 and 4 months Partial mastectomy with ALND/no recurrence or metastasis at 7 months Q/Neoadjuvant chemotherapy+ MRM with ALND/no recurrence or metastasis at 42 months
R, right; L, left; U, upper part; UOQ, upper outer quadrant; ESR, external superior area; ER, estrogen receptor; PR, progesterone receptor; *Positive value410 fmol/mg; IHC, immunohistochemistry; Q, quadrantectomy; ALND, axillary lymph node dissection; MRM, modified radical mastectomy.
ARTICLE IN PRESS Glycogen-rich clear cell mammary malignant myoepithelioma The differential diagnoses in the case of clear cell malignant myoepithelioma include glycogen-rich,2 lipid-rich,1 secretory,3 and signet ring cell carcinoma,4 clear cell variant of apocrine and argyrophilic carcinoma, and adenoid cystic carcinoma with sebaceous differentiation. The clear cells of these tumors, except for glycogen-rich carcinoma, are easily differentiated from those of myoepithelial carcinoma with special stains that identify glycogen, fat, mucin, and neurosecretory granules. Cytoplasmic vacuolization and clearing are features associated with atypical apocrine proliferations, and they are usually most prominent in apocrine carcinoma. The tumor cells of apocrine carcinoma contain diastase-resistant PAS-positive granules, and they tend to be positive for CEA and usually negative for S-100 protein. In contrast to apocrine carcinoma, the tumor cells of our patient showed diastase-labile PAS-positive granules, which were negative for CEA and positive for S-100 protein. Sebaceous neoplasms show positive for fat. However, in our case the tumor cells were negative on fat staining. No positive Grimelius reaction, positivity for NSE and chromogranin, or neurosecretory granules, which have been seen in endocrine mammary carcinoma, were found. The antibodies most commonly used for the identification of myoepithelial cells were CK, vimentin, SMA, S-100 proteins, and glial fibrillary acidic proteins. These antibodies are not specific for myoepithelial cells, but when applied together positive findings indicate myoepithelial differentiation with a reasonable degree of confidence. Moreover, cells of glycogen-rich carcinoma will not react with SMA. In the present case, tumor cells in the lesions showed a highly specific myoepithelial phenotype: co-expression of CK, EMA, SMA, S-100 protein, and vimentin in the same cells. Therefore, the tumor in the present case must have been of myoepithelial origin, or at least be myoepithelial in nature. The biological behavior of this type of tumor and the prognosis of the patient are not known because so few cases have been documented in the literature. It is essential to be able to recognize
509
clear cell malignant myoepithelioma, so that we can learn more about their natural history and how they respond to treatment.
References 1. Ramos CV, Taylor HB. Lipid-rich carcinoma of the breast: a clinicopathologic analysis of 13 examples. Cancer 1974; 33:812–9. 2. Hayes MMM, Seidman JD, Ashton MA. Glycogen-rich clear cell carcinoma of the breast: a clinicopathologic study of 21 cases. Am J Surg Pathol 1995. 3. Oberman HA. Secretory carcinoma of the breast in adults. Am J Surg Pathol 1980;4:465–70. 4. Merino MJ, Livolsi VA. Signet ring cell carcinoma of the female breast: a clinicopathologic analysis of 14 cases. Cancer 1981;48:1830–7. 5. Al-Nafussi A. Spindle cell tumors of the breast: practical approach to diagnosis. Histopathology 1999;35:1–13. 6. Cartagena Jr N, Cabello-Inchausti B, Willis I, Poppiti Jr. R. Clear cell myoepithelial neoplasm of the breast. Hum Pathol 1988;19:1239–43. 7. Soares J, Tomasic G, Bucciarelli E, Eusebi V. Intralobular growth of myoepithelial cell carcinoma of the breast. Virchows Arch 1994;425:205–10. 8. Kuwabara H, Uda H. Clear cell mammary malignant myoepithelioma with abundant glycogens. J Clin Pathol 1997;50:700–2. 9. Bloom HJG, Richardson WW. Histologic grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 1957;11: 359–77. 10. Tavassoli FA. Myoepithelial lesions of the breast: myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma. Am J Surg Pathol 1991;15:554–68. 11. Miura Y, Kurose A, Kondo M, Maruyama A, Shibata Y, Kanno H, Sawai T. Clear cell myoepithelial carcinoma of the breast: a case report. Tohoku J Exp Med 2003;200:103–9. 12. Torner PS, Kahn HJ, Baumal R, Lee K, Moffat W. Malignant myoepithelioma of the breast. An immunohistochemical study by light and electron microscopy. Cancer 1986;57: 745–50. 13. Hamperl H. The myoepithelia (myoepithelial cells). Normal state; regressive change; hyperplasia; tumors. Curr Top Pathol 1970;53:161–220. 14. Tamai M. Intraductal growth of malignant mammary myoepithelioma. Am J Surg Pathol 1992;16:1116–25. 15. Saksela E, Tarkkanen J, Wartiovaara J. Parotid clear-cell adenoma of possible myoepithelial origin. Cancer 1972;30: 742–8.