177
Breast Disease 34 (2014) 177–181 DOI 10.3233/BD-140366 IOS Press
Case Report
Mucinous carcinoma of breast with psammomatous calcification: Report of a rare case with extensive axillary metastases Shalini Bahadur, Mukta Pujani, Sujata Jetley∗ and Prabhat Kumar Raina Hamdard Institute of Medical Sciences and Research, New Delhi, India
Abstract. Pure mucinous carcinoma of the breast accounts for about 2% of all breast carcinomas and is associated with a favourable prognosis due to its lower nuclear grade and infrequent axillary or hematogenous metastases. Micropapillary variant of mucinous carcinoma breast has recently received attention as a unique form of invasive carcinoma of the breast exhibiting dual differentiation towards mucinous as well as micropapillary. The characteristic features for labeling a tumor as mucinous micropapillary carcinoma are micropapillary pattern, nuclear pleomorphism, hobnail cells and psammoma bodies in addition to the predominant mucinous component. Micropapillary mucinous carcinoma (MUMPC) when compared to pure mucinous carcinoma tends to have a higher nuclear grade, axillary lymph node metastases, lymphovascular invasion and overexpression of Her 2, p53 and Ki-67, thereby displaying an aggressive clinical behaviour. We present a rare case of micropapillary mucinous carcinoma to highlight the fact that this being a unique and rare variant of mucinous carcinoma should be recognized and reported as a separate category by the pathologists owing to its aggressive clinical behaviour and its influence on the nature of therapy. Keywords: Mucinous carcinoma, micropapillary, psammoma bodies, breast
1. Introduction Pure mucinous carcinoma of the breast is an unusual type of invasive carcinoma accounting for about 2% of all breast carcinomas and is considered to have a favourable prognosis owing to its lower nuclear grade and infrequent axillary or hematogenous metastases [1]. However, several recent studies [2–10] have documented an uncommon variant of mucinous carcinoma known as micropapillary mucinous carcinoma (MUMPC). The significance of identifying this entity lies in the fact that it has an aggressive clinical behavior com∗ Corresponding author: Sujata Jetley, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India. Tel.: +91 9350621681; E-mail: [email protected].
pared to the conventional mucinous carcinoma. We report a rare case of micropapillary mucinous carcinoma with psammomatous calcification to increase awareness of this unusual variant and its clinically adverse outcome among pathologists and clinicians.
2. Case summary A 53 years old female presented with a lump in the left breast for 2 months. On examination, a firm lump with irregular contours measuring 13 × 11 cm was palpable involving almost all the quadrants of left breast. The lump was fixed to the skin, not to the chest wall. Two left axillary lymph nodes were palpable measuring approximately 0.8 and 1 cm in diameter. There were no lumps in right breast or axilla. Systemic examination did not reveal any significant abnormality.
c 2011/2012 – IOS Press and the authors. All rights reserved 0888-6008/14/$27.50
178
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
Fig. 2. Photomicrograph showing tumor cells arranged in nests, floret-like clusters and pseudoacinar structures (black arrow) floating in pools of extracellular mucin alongwith psammoma bodies (white arrow with black borders) (Hematoxylin and Eosin, 100X). (Colours are visible in the online version of the article; http://dx.doi. org/10.3233/BD-140366)
Fig. 1. Grossly, tumor was grey white with a translucent, mucoid appearance. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/BD-140366)
Routine hematological and biochemical parameters were in normal range. Mammography revealed focal asymmetrical area of increased density with irregular shape and microcalcifications, located in inner quadrant of left breast with associated enlarged left axillary lymph node, suggestive of a mitotically active malignant tumor. Right breast showed fibrofatty breast parenchyma. A normal abdominal scan was obtained on ultrasonography. Bone scan did not reveal any definite evidence of skeletal metastasis. Tru cut biopsy was performed and a diagnosis of mucinous carcinoma was given. There was no evidence of calcification or micropapillary arrangement. The patient was given 3 cycles of neoadjuvant chemotherapy comprising of docetaxel and cyclophosphamide. There was a partial response to chemotherapy as the tumor showed less than 50% reduction in its size. A left modified radical mastectomy was performed and specimen sent for histopathology. Grossly, tumor was grey white with a translucent, mucoid appearance measuring 11 × 8 × 6 cm. Tumor was 1 cm away from deep resection plane (Fig. 1). One section per cm diameter of the tumor was processed, so a total of 11 sections from the tumor were taken. Microscopic examination revealed a tumor composed of cells arranged in nests, floret-like clusters and pseudoacinar structures with frayed borders floating
in pools of extracellular mucin (Fig. 2). Characteristic hobnail cells were also seen (Fig. 3) with many areas of psammomatous calcification. The nuclei were moderately pleomorphic (grade 2) and there were 7– 8 mitoses per 10 high power fields. There was no evidence of non mucinous component. Moreover, there were no areas of necrosis or fibrosis that could be regarded as chemotherapy related changes. The deep resection plane showed tumor emboli in the vessels. The tumor also infiltrated the dermis and was seen to reach just below the epidermis. There was no evidence of in situ carcinoma in the adjoining breast tissue. 15 out of a total of 16 lymph nodes isolated, showed tumor metastases with similar mucinous morphology as in the primary tumor (15/16) (Fig. 4). Pathological stage of the tumor (following neoadjuvant chemotherapy) was yT4b N3 Mx. A final diagnosis of micropapillary mucinous carcinoma breast was rendered with a Nottingham’s modification of Bloom Richardson’s grade II. On immunohistochemistry, estrogen and progesterone receptors (ER, PR) were positive while Her 2 was negative. Epithelial membrane antigen (EMA) showed strong membranous positivity with a reverse inside out pattern (that is instead of strong luminal staining, abluminal staining is more prominent). Ki-67 labelling index was 15– 20% in both the pretreatment biopsy as well as postneoadjuvant chemotherapy tumor tissue while p53 was found to be positive in only a few cells. Post surgery, the patient was given 3 additional cycles of chemotherapy (same regime) followed by lo-
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
179
Fig. 3. Photomicrograph showing floret-like clusters and pseudoacinar structures with hobnailing (arrows), (Hematoxylin and Eosin, 400X). (Colours are visible in the online version of the article; http://dx. doi.org/10.3233/BD-140366)
Fig. 4. Photomicrograph showing lymph node metastasis from mucinous micropapillary carcinoma (Hematoxylin and Eosin, 100X). (Colours are visible in the online version of the article; http://dx.doi. org/10.3233/BD-140366)
cal radiotherapy and hormonal therapy (aromatase inhibitor). On first followup after 3 months, there was no evidence of recurrence or distant metastasis.
psammomatous calcifications [10]. In the present case, almost all of these features were observed. Diagnosing a micropapillary mucinous carcinoma on a trucut biopsy is quite challenging due to the small size of the tissue. However, on encountering calcification or pseudoacinar structures one should be alerted towards the possibility of micropapillary variant of mucinous carcinoma. In our case, there was no evidence of calcification or micropapillary structures or any specific type of infiltrating ductal carcinoma. Another limitation is post neo-adjuvant chemotherapy specimens. Chemotherapy related changes like fibrosis, absence of residual tumor or disappearance of one of the components in a mixed tumor (due to differential response to chemotherapy) can create difficulties in accurate diagnosis. The clinical significance of this morphological entity is still not very clear as only a few studies have been reported. Pettinato et al. [4] reviewed invasive micropapillary carcinoma cases and found that 87% of these were grade 3, 47% showed presence of psammoma bodies, 63% revealed lymphatic invasion, 90% had metastatic axillary nodes, Her 2 was overexpressed in 95% cases while p53 was overexpressed in 70% cases. Lin et al. [9] studied the clinicopathologic features of 26 cases of micropapillary variant of pure mucinous carcinoma of breast. They observed that mucinous carcinoma with micropapillary pattern showed different nuclear grades (grade I – 19 cases, grade II – 2 cases and grade III – 5 cases) compared to conventional pure mucinous carcinoma. Out of a total of 26 cases, calcification and psammoma bodies were observed in 8
3. Discussion Micropapillary mucinous carcinoma of breast has recently received recognition as a unique form of invasive carcinoma breast exhibiting features of both mucinous as well as micropapillary differentiation. Mucinous micropapillary carcinoma accounts for less than 1% of all breast carcinomas [10]. The pathogenetic relationship of micropapillary mucinous carcinoma to conventional mucinous or micropapillary carcinomas has not been established. There is an unresolved dilemma whether MUMPC represents “a mucinous variant of micropapillary carcinoma” or “a micropapillary variant of mucinous carcinoma”. A few authors [11,12] have reported micropapillary mucinous carcinoma based on cytological findings alone which were later confirmed histopathologically. Both benign and malignant breast lesions can display microcalcifications, however, the occurrence of psammoma bodies in breast lesions is a rare phenomenon and has been observed usually in papillary neoplasms [11]. The salient features to label a mucinous carcinoma as a micropapillary variant include: (1) predominantly mucinous appearance (> 90% mucinous component), (2) tumor cells forming a distinctive micropapillary pattern, (3) presence of hobnail cells, (4) nuclear grade-frequently intermediate to high and (5) frequent
180
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
cases. On immunophenotyping, there was higher expression of hormone receptors in tumor cells while Her 2 was negative. 6 cases revealed neuroendocrine differentiation while axillary lymph node metastasis was identified in 3 patients and cutaneous involvement in 2 patients. Barbashina et al. [10] studied 15 cases of this rare mucinous micropapillary carcinoma to highlight the differences, if any, between this rare variant and conventional pure mucinous carcinoma. They observed Her 2 positivity in 20% cases and p53 positivity in 23% cases. 60% of mucinous micropapillary carcinoma cases demonstrated lymphovascular invasion while axillary lymph node metastases was observed in 33% patients. Based on these findings, they concluded that mucinous micropapillary carcinoma is a clinically aggressive variant of mucinous carcinoma. On the contrary, Bal et al. [5] found 6 cases of mucinous carcinoma with diffuse micropapillary pattern over a period of 10 years with all the cases having grade I nuclear morphology, negativity for Her 2 and no lymph node metastasis. Their findings were similar to conventional pure mucinous carcinoma. Taking into account the observations of these studies, it is therefore very important that this rare morphological variant be recognized as a distinct entity from the conventional pure mucinous carcinoma breast. The pathognomonic features for labeling a tumor as mucinous micropapillary carcinoma are a combination of micropapillary pattern, nuclear pleomorphism and hobnail cells in addition to the predominant mucinous component. The presence of psammoma bodies is another clue towards the diagnosis of micropapillary mucinous carcinoma, seen in 17–53% cases [4,9,10]. The clinically aggressive nature of mucinous micropapillary carcinoma breast could be a reflection of its dual differentiation (mucinous as well as micropapillary). MUMPC when compared to pure mucinous carcinoma tends to have a higher nuclear grade, axillary lymph node metastases and lymphovascular invasion. In the present case, the patient had metastases in most of axillary nodes. Moreover, the biomarker expression is also indicative of dual phenotype of this tumor. Barbashina et al. [10] have reported a higher incidence of Her 2 expression, Ki-67 labelling index and p53 positivity in MUMPC compared to pure mucinous carcinoma. Petersen [13] attributed the characteristic architecture of micropapillary carcinoma of the breast to a rotation of cell polarization also known as an inside out growth pattern. This was visualized as an inverted
membrane cytoplasmic immunoreactivity for EMA or MUC1 towards the stroma instead of luminal side by several authors [4,6]. On the contrary, in a recent study Barbashina et al stated that the reversed “inside-out” pattern of surface glycoproteins was not helpful in mucin producing micropapillary carcinomas of breast as the same pattern is also observed in pure mucinous carcinomas. To conclude, we wish to highlight that micropapillary mucinous carcinoma being a unique and rare variant of mucinous carcinoma should be recognized and reported as a separate category by the pathologists owing to its aggressive clinical behavior and its influence on the nature of therapy.
References [1]
Tavassoli FA, Devilee P, World Health Organization. Pathology and genetics of tumours of the breast and female genital organs. World Health Organization classification of tumours. Lyon: IAPS Press; 2003. p. 30-1. [2] Pettinato G, Manivel JC, Panico L, et al. Pseudopapillary (serous-like) carcinoma of the breast: An aggressive variant of ductal carcinoma [abstract]. Mod Pathol. 1991; 4: 13A. [3] Ng WK. Fine-needle aspiration cytology findings of an uncommon micropapillary variant of pure mucinous carcinoma of the breast: Review of patients over an 8-year period. Cancer 2002; 96: 280-8. [4] Pettinato G, Manivel CJ, Panico L, Sparano L, Petrella G. Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. Am J Clin Pathol 2004; 121: 85766. [5] Bal A, Joshi K, Sharma SC, Das A, Verma A, Wig JD. Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast. Int J Surg Pathol 2008; 16: 251-6. [6] Shet T, Chinoy R. Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior. Breast J 2008; 14: 412-20. [7] Rao P, Lyons B. Pure mucinous carcinoma of the breast with extensive psammomatous calcification. Histopathology 2008; 52: 650-2. [8] Ranade A, Batra R, Sandhu G, Chitale RA, Balderacchi J. Clinicopathological evaluation of 100 cases of mucinous carcinoma of breast with emphasis on axillary staging and special reference to a micropapillary pattern. J Clin Pathol 2010; 63: 1043-7. [9] Lin HY, Gao LX, Jin ML, Ding HY. Clinicopathologic features of micropapillary variant of pure mucinous carcinoma of breast. Chin J Pathol (Zhonghua Bing Li Xue Za Zhi) 2012; 41(9): 613-7. [10] Barbashina V, Corben AD, Akram M, Vallejo C, Tan LK. Mucinous micropapillary carcinoma of the breast: an aggressive counterpart to conventional pure mucinous tumors. Human Pathol 2013; DOI:10.1016/j.humpath.2013.01.003 [11] Pillai KR, Jayasree K, Jayalal KS, Mani KS, Abraham EK. Mucinous carcinoma of breast with abundant psammoma bodies in fine-needle aspiration cytology: a case report. Diagnostic cytopathology 2007; 35(4): 230-3.
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast [12]
Jain S, Khurana N, Rao S, Garg A, Kaza RCM. Psammomatous Colloid Carcinoma of the Breast with Micropapillary Pattern. The Breast Journal 2012; 18(2): 178-80.
[13]
181
Petersen JL. Breast carcinomas with an unexpected inside out growth pattern: rotation of polarization associated with angioinvasion [abstract]. Pathol Res Pract 1993; 189: 780.
Copyright of Breast Disease is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Breast Disease 34 (2014) 177–181 DOI 10.3233/BD-140366 IOS Press
Case Report
Mucinous carcinoma of breast with psammomatous calcification: Report of a rare case with extensive axillary metastases Shalini Bahadur, Mukta Pujani, Sujata Jetley∗ and Prabhat Kumar Raina Hamdard Institute of Medical Sciences and Research, New Delhi, India
Abstract. Pure mucinous carcinoma of the breast accounts for about 2% of all breast carcinomas and is associated with a favourable prognosis due to its lower nuclear grade and infrequent axillary or hematogenous metastases. Micropapillary variant of mucinous carcinoma breast has recently received attention as a unique form of invasive carcinoma of the breast exhibiting dual differentiation towards mucinous as well as micropapillary. The characteristic features for labeling a tumor as mucinous micropapillary carcinoma are micropapillary pattern, nuclear pleomorphism, hobnail cells and psammoma bodies in addition to the predominant mucinous component. Micropapillary mucinous carcinoma (MUMPC) when compared to pure mucinous carcinoma tends to have a higher nuclear grade, axillary lymph node metastases, lymphovascular invasion and overexpression of Her 2, p53 and Ki-67, thereby displaying an aggressive clinical behaviour. We present a rare case of micropapillary mucinous carcinoma to highlight the fact that this being a unique and rare variant of mucinous carcinoma should be recognized and reported as a separate category by the pathologists owing to its aggressive clinical behaviour and its influence on the nature of therapy. Keywords: Mucinous carcinoma, micropapillary, psammoma bodies, breast
1. Introduction Pure mucinous carcinoma of the breast is an unusual type of invasive carcinoma accounting for about 2% of all breast carcinomas and is considered to have a favourable prognosis owing to its lower nuclear grade and infrequent axillary or hematogenous metastases [1]. However, several recent studies [2–10] have documented an uncommon variant of mucinous carcinoma known as micropapillary mucinous carcinoma (MUMPC). The significance of identifying this entity lies in the fact that it has an aggressive clinical behavior com∗ Corresponding author: Sujata Jetley, Hamdard Institute of Medical Sciences and Research (HIMSR), Jamia Hamdard, New Delhi, India. Tel.: +91 9350621681; E-mail: [email protected].
pared to the conventional mucinous carcinoma. We report a rare case of micropapillary mucinous carcinoma with psammomatous calcification to increase awareness of this unusual variant and its clinically adverse outcome among pathologists and clinicians.
2. Case summary A 53 years old female presented with a lump in the left breast for 2 months. On examination, a firm lump with irregular contours measuring 13 × 11 cm was palpable involving almost all the quadrants of left breast. The lump was fixed to the skin, not to the chest wall. Two left axillary lymph nodes were palpable measuring approximately 0.8 and 1 cm in diameter. There were no lumps in right breast or axilla. Systemic examination did not reveal any significant abnormality.
c 2011/2012 – IOS Press and the authors. All rights reserved 0888-6008/14/$27.50
178
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
Fig. 2. Photomicrograph showing tumor cells arranged in nests, floret-like clusters and pseudoacinar structures (black arrow) floating in pools of extracellular mucin alongwith psammoma bodies (white arrow with black borders) (Hematoxylin and Eosin, 100X). (Colours are visible in the online version of the article; http://dx.doi. org/10.3233/BD-140366)
Fig. 1. Grossly, tumor was grey white with a translucent, mucoid appearance. (Colours are visible in the online version of the article; http://dx.doi.org/10.3233/BD-140366)
Routine hematological and biochemical parameters were in normal range. Mammography revealed focal asymmetrical area of increased density with irregular shape and microcalcifications, located in inner quadrant of left breast with associated enlarged left axillary lymph node, suggestive of a mitotically active malignant tumor. Right breast showed fibrofatty breast parenchyma. A normal abdominal scan was obtained on ultrasonography. Bone scan did not reveal any definite evidence of skeletal metastasis. Tru cut biopsy was performed and a diagnosis of mucinous carcinoma was given. There was no evidence of calcification or micropapillary arrangement. The patient was given 3 cycles of neoadjuvant chemotherapy comprising of docetaxel and cyclophosphamide. There was a partial response to chemotherapy as the tumor showed less than 50% reduction in its size. A left modified radical mastectomy was performed and specimen sent for histopathology. Grossly, tumor was grey white with a translucent, mucoid appearance measuring 11 × 8 × 6 cm. Tumor was 1 cm away from deep resection plane (Fig. 1). One section per cm diameter of the tumor was processed, so a total of 11 sections from the tumor were taken. Microscopic examination revealed a tumor composed of cells arranged in nests, floret-like clusters and pseudoacinar structures with frayed borders floating
in pools of extracellular mucin (Fig. 2). Characteristic hobnail cells were also seen (Fig. 3) with many areas of psammomatous calcification. The nuclei were moderately pleomorphic (grade 2) and there were 7– 8 mitoses per 10 high power fields. There was no evidence of non mucinous component. Moreover, there were no areas of necrosis or fibrosis that could be regarded as chemotherapy related changes. The deep resection plane showed tumor emboli in the vessels. The tumor also infiltrated the dermis and was seen to reach just below the epidermis. There was no evidence of in situ carcinoma in the adjoining breast tissue. 15 out of a total of 16 lymph nodes isolated, showed tumor metastases with similar mucinous morphology as in the primary tumor (15/16) (Fig. 4). Pathological stage of the tumor (following neoadjuvant chemotherapy) was yT4b N3 Mx. A final diagnosis of micropapillary mucinous carcinoma breast was rendered with a Nottingham’s modification of Bloom Richardson’s grade II. On immunohistochemistry, estrogen and progesterone receptors (ER, PR) were positive while Her 2 was negative. Epithelial membrane antigen (EMA) showed strong membranous positivity with a reverse inside out pattern (that is instead of strong luminal staining, abluminal staining is more prominent). Ki-67 labelling index was 15– 20% in both the pretreatment biopsy as well as postneoadjuvant chemotherapy tumor tissue while p53 was found to be positive in only a few cells. Post surgery, the patient was given 3 additional cycles of chemotherapy (same regime) followed by lo-
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
179
Fig. 3. Photomicrograph showing floret-like clusters and pseudoacinar structures with hobnailing (arrows), (Hematoxylin and Eosin, 400X). (Colours are visible in the online version of the article; http://dx. doi.org/10.3233/BD-140366)
Fig. 4. Photomicrograph showing lymph node metastasis from mucinous micropapillary carcinoma (Hematoxylin and Eosin, 100X). (Colours are visible in the online version of the article; http://dx.doi. org/10.3233/BD-140366)
cal radiotherapy and hormonal therapy (aromatase inhibitor). On first followup after 3 months, there was no evidence of recurrence or distant metastasis.
psammomatous calcifications [10]. In the present case, almost all of these features were observed. Diagnosing a micropapillary mucinous carcinoma on a trucut biopsy is quite challenging due to the small size of the tissue. However, on encountering calcification or pseudoacinar structures one should be alerted towards the possibility of micropapillary variant of mucinous carcinoma. In our case, there was no evidence of calcification or micropapillary structures or any specific type of infiltrating ductal carcinoma. Another limitation is post neo-adjuvant chemotherapy specimens. Chemotherapy related changes like fibrosis, absence of residual tumor or disappearance of one of the components in a mixed tumor (due to differential response to chemotherapy) can create difficulties in accurate diagnosis. The clinical significance of this morphological entity is still not very clear as only a few studies have been reported. Pettinato et al. [4] reviewed invasive micropapillary carcinoma cases and found that 87% of these were grade 3, 47% showed presence of psammoma bodies, 63% revealed lymphatic invasion, 90% had metastatic axillary nodes, Her 2 was overexpressed in 95% cases while p53 was overexpressed in 70% cases. Lin et al. [9] studied the clinicopathologic features of 26 cases of micropapillary variant of pure mucinous carcinoma of breast. They observed that mucinous carcinoma with micropapillary pattern showed different nuclear grades (grade I – 19 cases, grade II – 2 cases and grade III – 5 cases) compared to conventional pure mucinous carcinoma. Out of a total of 26 cases, calcification and psammoma bodies were observed in 8
3. Discussion Micropapillary mucinous carcinoma of breast has recently received recognition as a unique form of invasive carcinoma breast exhibiting features of both mucinous as well as micropapillary differentiation. Mucinous micropapillary carcinoma accounts for less than 1% of all breast carcinomas [10]. The pathogenetic relationship of micropapillary mucinous carcinoma to conventional mucinous or micropapillary carcinomas has not been established. There is an unresolved dilemma whether MUMPC represents “a mucinous variant of micropapillary carcinoma” or “a micropapillary variant of mucinous carcinoma”. A few authors [11,12] have reported micropapillary mucinous carcinoma based on cytological findings alone which were later confirmed histopathologically. Both benign and malignant breast lesions can display microcalcifications, however, the occurrence of psammoma bodies in breast lesions is a rare phenomenon and has been observed usually in papillary neoplasms [11]. The salient features to label a mucinous carcinoma as a micropapillary variant include: (1) predominantly mucinous appearance (> 90% mucinous component), (2) tumor cells forming a distinctive micropapillary pattern, (3) presence of hobnail cells, (4) nuclear grade-frequently intermediate to high and (5) frequent
180
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast
cases. On immunophenotyping, there was higher expression of hormone receptors in tumor cells while Her 2 was negative. 6 cases revealed neuroendocrine differentiation while axillary lymph node metastasis was identified in 3 patients and cutaneous involvement in 2 patients. Barbashina et al. [10] studied 15 cases of this rare mucinous micropapillary carcinoma to highlight the differences, if any, between this rare variant and conventional pure mucinous carcinoma. They observed Her 2 positivity in 20% cases and p53 positivity in 23% cases. 60% of mucinous micropapillary carcinoma cases demonstrated lymphovascular invasion while axillary lymph node metastases was observed in 33% patients. Based on these findings, they concluded that mucinous micropapillary carcinoma is a clinically aggressive variant of mucinous carcinoma. On the contrary, Bal et al. [5] found 6 cases of mucinous carcinoma with diffuse micropapillary pattern over a period of 10 years with all the cases having grade I nuclear morphology, negativity for Her 2 and no lymph node metastasis. Their findings were similar to conventional pure mucinous carcinoma. Taking into account the observations of these studies, it is therefore very important that this rare morphological variant be recognized as a distinct entity from the conventional pure mucinous carcinoma breast. The pathognomonic features for labeling a tumor as mucinous micropapillary carcinoma are a combination of micropapillary pattern, nuclear pleomorphism and hobnail cells in addition to the predominant mucinous component. The presence of psammoma bodies is another clue towards the diagnosis of micropapillary mucinous carcinoma, seen in 17–53% cases [4,9,10]. The clinically aggressive nature of mucinous micropapillary carcinoma breast could be a reflection of its dual differentiation (mucinous as well as micropapillary). MUMPC when compared to pure mucinous carcinoma tends to have a higher nuclear grade, axillary lymph node metastases and lymphovascular invasion. In the present case, the patient had metastases in most of axillary nodes. Moreover, the biomarker expression is also indicative of dual phenotype of this tumor. Barbashina et al. [10] have reported a higher incidence of Her 2 expression, Ki-67 labelling index and p53 positivity in MUMPC compared to pure mucinous carcinoma. Petersen [13] attributed the characteristic architecture of micropapillary carcinoma of the breast to a rotation of cell polarization also known as an inside out growth pattern. This was visualized as an inverted
membrane cytoplasmic immunoreactivity for EMA or MUC1 towards the stroma instead of luminal side by several authors [4,6]. On the contrary, in a recent study Barbashina et al stated that the reversed “inside-out” pattern of surface glycoproteins was not helpful in mucin producing micropapillary carcinomas of breast as the same pattern is also observed in pure mucinous carcinomas. To conclude, we wish to highlight that micropapillary mucinous carcinoma being a unique and rare variant of mucinous carcinoma should be recognized and reported as a separate category by the pathologists owing to its aggressive clinical behavior and its influence on the nature of therapy.
References [1]
Tavassoli FA, Devilee P, World Health Organization. Pathology and genetics of tumours of the breast and female genital organs. World Health Organization classification of tumours. Lyon: IAPS Press; 2003. p. 30-1. [2] Pettinato G, Manivel JC, Panico L, et al. Pseudopapillary (serous-like) carcinoma of the breast: An aggressive variant of ductal carcinoma [abstract]. Mod Pathol. 1991; 4: 13A. [3] Ng WK. Fine-needle aspiration cytology findings of an uncommon micropapillary variant of pure mucinous carcinoma of the breast: Review of patients over an 8-year period. Cancer 2002; 96: 280-8. [4] Pettinato G, Manivel CJ, Panico L, Sparano L, Petrella G. Invasive micropapillary carcinoma of the breast: clinicopathologic study of 62 cases of a poorly recognized variant with highly aggressive behavior. Am J Clin Pathol 2004; 121: 85766. [5] Bal A, Joshi K, Sharma SC, Das A, Verma A, Wig JD. Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast. Int J Surg Pathol 2008; 16: 251-6. [6] Shet T, Chinoy R. Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior. Breast J 2008; 14: 412-20. [7] Rao P, Lyons B. Pure mucinous carcinoma of the breast with extensive psammomatous calcification. Histopathology 2008; 52: 650-2. [8] Ranade A, Batra R, Sandhu G, Chitale RA, Balderacchi J. Clinicopathological evaluation of 100 cases of mucinous carcinoma of breast with emphasis on axillary staging and special reference to a micropapillary pattern. J Clin Pathol 2010; 63: 1043-7. [9] Lin HY, Gao LX, Jin ML, Ding HY. Clinicopathologic features of micropapillary variant of pure mucinous carcinoma of breast. Chin J Pathol (Zhonghua Bing Li Xue Za Zhi) 2012; 41(9): 613-7. [10] Barbashina V, Corben AD, Akram M, Vallejo C, Tan LK. Mucinous micropapillary carcinoma of the breast: an aggressive counterpart to conventional pure mucinous tumors. Human Pathol 2013; DOI:10.1016/j.humpath.2013.01.003 [11] Pillai KR, Jayasree K, Jayalal KS, Mani KS, Abraham EK. Mucinous carcinoma of breast with abundant psammoma bodies in fine-needle aspiration cytology: a case report. Diagnostic cytopathology 2007; 35(4): 230-3.
S. Bahadur et al. / Micropapillary mucinous carcinoma of breast [12]
Jain S, Khurana N, Rao S, Garg A, Kaza RCM. Psammomatous Colloid Carcinoma of the Breast with Micropapillary Pattern. The Breast Journal 2012; 18(2): 178-80.
[13]
181
Petersen JL. Breast carcinomas with an unexpected inside out growth pattern: rotation of polarization associated with angioinvasion [abstract]. Pathol Res Pract 1993; 189: 780.
Copyright of Breast Disease is the property of IOS Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
