CORRESPONDENCE
calponin and smooth muscle actin.4,9,11–12 TTF1 is not expressed and the Ki-67 proliferation index is low.10 ES has an unclear aetiology. In the abdomen, ES may be the result of mu¨llerian metaplasia of pelvic peritoneal mesothelium or submesothelium, the most commonly accepted theory. Alternatively, it could arise from peritoneal implantation of sloughed or surgically displaced fallopian tube epithelium. Lymphatic dissemination of shed tubal epithelium or of metaplastic peritoneal mesothelium may explain its presence within lymph nodes.3,9 In this case, the ES did not transfer on imprint cytology and it was recognised in routine histological examination. Although the epithelium within the other lymph node could not be further assessed immunohistochemically because it cut out in deeper levels, the histological appearance was not typical of ES. Knowledge of the rare possibility of ES in axillary lymph nodes is important as it may potentially lead to unnecessary axillary lymph node dissection with its inherent morbidity. Acknowledgements: With thanks to Merran McKesser. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. Mark Wilsher1 Kylie L. Snook2 1
Douglass Hanly Moir Pathology, Macquarie Park, and Breast and Surgical Oncology at the Poche Centre, North Sydney, NSW, Australia
2
Contact Dr M. Wilsher. E-mail: [email protected] 1. Iken S, Schmidt M, Braun C, et al. Absence of ectopic epithelial inclusions in 3,904 axillary lymph nodes examined in sentinel technique. Breast Cancer Res Treat 2012; 132: 621–4. 2. Sawicki MP, Howard TJ, Passaro E. Heterotopic tissue in lymph nodes. An unrecognized problem. Arch Surg 1990; 125: 1394–9. 3. Spinardi JR, Goncalves IRD, La Falce TS, et al. Benign inclusions in lymph nodes. Int J Morphol 2007; 25: 625–9. 4. Fellegara G, Carcangiu ML, Rosai J. Benign epithelial inclusions in axillary lymph nodes: report of 18 cases and review of the literature. Am J Surg Pathol 2011; 35: 1123–33. 5. Henley JD, Michael HB, English GW, et al. Benign mu¨llerian lymph node inclusions. An unusual case with implications for pathogenesis and review of the literature. Arch Pathol Lab Med 1995; 119: 841–4. 6. Piana S, Asioli S, Cavazza A. Benign Mu¨llerian inclusions coexisting with breast metastatic carcinoma in an axillary lymph node. Virchows Arch 2005; 446: 467–9. 7. Norton LE1, Komenaka IK, Emerson RE, et al. Benign glandular inclusions a rare cause of a false positive sentinel node. J Surg Oncol 2007; 95: 593–6. 8. Peng Y, Ashfaq R, Ewing G, et al. False-positive sentinel lymph nodes in breast cancer patients caused by benign glandular inclusions: report of three cases and review of the literature. Am J Clin Pathol 2008; 130: 21–7. 9. Corben AD, Nehhozina T, Garg K, et al. Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. Am J Surg Pathol 2010; 34: 1211–6. 10. Stolnicu S, Preda O, Kinga S, et al. Florid, papillary endosalpingiosis of the axillary lymph nodes. Breast J 2011; 17: 268–72. 11. Sarode VR, Euhus D, Thompson M, et al. Atypical endosalpingiosis in axillary sentinel lymph node: a potential source of false-positive diagnosis of metastasis. Breast J 2011; 17: 672–3. 12. Salehi AH, Omeroglu G, Kanber Y, et al. Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall. Int J Surg Pathol 2013; 21: 610–2.
667
13. Lakhani SR, Ellis IO, Schnitt SJ, et al. WHO Classification of Tumours of the Breast. 4th ed. Lyon: IARC, 2012; Chapter 7, Intraductal papillary lesions.
DOI: 10.1097/PAT.0000000000000173
Mammary analogue secretory carcinoma of minor salivary glands Sir, Mammary analogue secretory carcinoma (MASC) is a recently described distinctive salivary gland neoplasm with similar morphological and immunohistochemical attributes to secretory carcinoma (SC) of the breast.1 Prior to its description in 2010, MASC used to be regarded as one of a number of known benign and malignant salivary gland tumours.2,3 MASC is usually low grade but high grade transformation has recently been described.4 A case of MASC in the upper lip is presented and the differential diagnosis of this intriguing tumour is discussed. A 66-year-old man presented with a 6 month history of thickening associated with swelling on the inner surface of the upper lip. The swelling which was subject to accidental biting fluctuated in size. On examination, a mass which was thought to represent minor salivary gland tumour was found. The mass was excised and the patient is being clinically followed up with no evidence of disease recurrence. The resected specimen consisted of a mucosal covered piece of tissue 12 10 8 mm. The cut surface showed a partly cystic, brown, 10 mm nodule. An encapsulated partly cystic tumour was seen microscopically (Fig. 1A). The tumour was made up of eosinophilic cells with glandular areas and microcystic spaces (Fig. 1B,C). The central part of the tumour showed degeneration and necrosis (Fig. 1A). Haemosiderin deposition attributed to occasional accidental biting by the patient was seen in parts of the tumour. The tumour cells appeared ‘oncocytic’ with round to oval nuclei and granular eosinophilic cytoplasm (Fig. 1D,E). Mild nuclear atypia was seen but mitoses were very rare. Globular eosinophilic material was present in the cytoplasm of some of the tumour cells and slightly basophilic material was noted in most of the microcystic spaces (Fig. 1E). Neutral and acidic mucinous material was noted in a few cells. Most of the cells also showed periodic acid Schiff (PAS) positivity, accounting for the ‘oncocytic’ appearance in the routine sections. The adjacent minor salivary glands and the overlying surface epithelium were normal. The lines of excision were clear. The tumour cells were positive for gross cystic disease fluid protein 15 (GCDFP-15; Fig. 2A), S100 (Fig. 2B), mammaglobin A (Fig. 2C) and MUC4 (Fig. 2D). Carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), vimentin, P63, b-catenin and cyclin D1 were also positive. Oestrogen, progesterone, human epidermal growth factor 2 and epidermal growth factor 1 were not expressed. Cytokeratin 7 was positive but cytokeratin 20 was negative. The tumour had a low proliferative index with up to 5% of the cells expressing MIB-1. Therefore, the tumour showed all the attributes of MASC. MASC was previously most often diagnosed as adenocarcinoma NOS, acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), polymorphous low grade adenocarcinoma and cystadenocarcinoma or cystadenoma.2,3 Cystadenoma and
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
668
Pathology (2014), 46(7), December
CORRESPONDENCE
A
H&E ×1
B
H&E ×4
C
D
H&E ×40
E
H&E ×20
H&E ×60
Fig. 1 Histological and histochemical properties of the lesion. (A) Three cross sections of the tumour. The tumour is circumscribed with cystic change and eosinophilic luminal contents. (B) Part of an encapsulated lesion (right) and normal minor salivary glandular tissue (upper left). The tumour displays a microcystic growth pattern. (C) Higher magnification of the tumour showing eosinophilic (right) and slightly basophilic cells (left). (D,E) Large eosinophilic cells with pseudoglandular growth pattern. The cells have oval to spindle shaped mildly atypical nuclei. An eosinophilic globule is seen in an oval space (centre, E) and slightly basophilic material is present within other spaces.
ACC were the initial differential diagnoses in this case. Indeed, Williams and Chiosea estimate that as many as 8% of salivary cystadenomas may represent cases of MASC.5 The majority of cases in the initial report were located in the parotid gland.1 Subsequent reports have shown that while the parotid gland is the most common site of origin, MASC may also arise in the other major salivary glands and the oral cavity, including the lip, buccal mucosa and soft palate. MASC usually shows a number of growth patterns including cystic, tubular, solid or papillary architecture. Eosinophilic cytoplasm, intraluminal or intracytoplasmic colloid-like secretions that stain positive for PAS and are diastase resistant are usually seen.2,3 The morphological spectrum of MASC has grown to include tumours with both macrocystic and microcystic areas, intracystic papillary patterns and solid areas, and the morphological differential diagnosis of MASC may be broader than previously considered, especially on small biopsy material.3 Other tumour types that may show similar architectural patterns include polymorphous low grade adenocarcinoma and adenoid cystic carcinoma.4 Immunohistochemically MASC shows positivity with numerous antibodies; the most useful being mammaglobin, MUC4 and S100. Mammaglobin immunoreactivity has been found in 55% of all salivary gland tumours.6 Mammaglobin positivity alone is not diagnostic of MASC. MUC4 has been reported in >80% of cases of MASC.7 MUC4 has also
been shown to be positive in MEC and MUC4 positivity in MEC has been associated with increased risk of recurrence and death.7 The prognostic value of MUC4 in MASC is unclear. S100 is variably expressed in many salivary gland tumours, particularly those with a myoepithelial element. Co-expression of S100 with mammaglobin has been regarded as a very useful marker in identifying MASC.8 However, these markers have also been shown to be expressed by the morphological mimics of MASC.2 Most studies have detected a low proliferation index by Ki-67 staining with 5–28% of MASC tumour cells expressing this marker.4 This tumour also had a low proliferative index with not more than 5% of the tumour cells expressing MIB1. MASC usually presents as a slow-growing, painless mass in adults.3 The tumour in our patient, in line with the majority of previously described cases, was circumscribed and completely encapsulated. Poor circumscription, infiltrative growth or invasion has been noted in about one-quarter of the cases.5 MASC has an overall favourable outcome but like ACC and other low-grade salivary gland carcinomas, MASC does have the capacity to occasionally behave aggressively in the form of recurrences, regional lymph node metastases, and even disease-related deaths.4 Currently there is no way to definitively predict the behaviour of MSAC. This is largely because MASC is such a rare tumour, accounting for
calponin and smooth muscle actin.4,9,11–12 TTF1 is not expressed and the Ki-67 proliferation index is low.10 ES has an unclear aetiology. In the abdomen, ES may be the result of mu¨llerian metaplasia of pelvic peritoneal mesothelium or submesothelium, the most commonly accepted theory. Alternatively, it could arise from peritoneal implantation of sloughed or surgically displaced fallopian tube epithelium. Lymphatic dissemination of shed tubal epithelium or of metaplastic peritoneal mesothelium may explain its presence within lymph nodes.3,9 In this case, the ES did not transfer on imprint cytology and it was recognised in routine histological examination. Although the epithelium within the other lymph node could not be further assessed immunohistochemically because it cut out in deeper levels, the histological appearance was not typical of ES. Knowledge of the rare possibility of ES in axillary lymph nodes is important as it may potentially lead to unnecessary axillary lymph node dissection with its inherent morbidity. Acknowledgements: With thanks to Merran McKesser. Conflicts of interest and sources of funding: The authors state that there are no conflicts of interest to disclose. Mark Wilsher1 Kylie L. Snook2 1
Douglass Hanly Moir Pathology, Macquarie Park, and Breast and Surgical Oncology at the Poche Centre, North Sydney, NSW, Australia
2
Contact Dr M. Wilsher. E-mail: [email protected] 1. Iken S, Schmidt M, Braun C, et al. Absence of ectopic epithelial inclusions in 3,904 axillary lymph nodes examined in sentinel technique. Breast Cancer Res Treat 2012; 132: 621–4. 2. Sawicki MP, Howard TJ, Passaro E. Heterotopic tissue in lymph nodes. An unrecognized problem. Arch Surg 1990; 125: 1394–9. 3. Spinardi JR, Goncalves IRD, La Falce TS, et al. Benign inclusions in lymph nodes. Int J Morphol 2007; 25: 625–9. 4. Fellegara G, Carcangiu ML, Rosai J. Benign epithelial inclusions in axillary lymph nodes: report of 18 cases and review of the literature. Am J Surg Pathol 2011; 35: 1123–33. 5. Henley JD, Michael HB, English GW, et al. Benign mu¨llerian lymph node inclusions. An unusual case with implications for pathogenesis and review of the literature. Arch Pathol Lab Med 1995; 119: 841–4. 6. Piana S, Asioli S, Cavazza A. Benign Mu¨llerian inclusions coexisting with breast metastatic carcinoma in an axillary lymph node. Virchows Arch 2005; 446: 467–9. 7. Norton LE1, Komenaka IK, Emerson RE, et al. Benign glandular inclusions a rare cause of a false positive sentinel node. J Surg Oncol 2007; 95: 593–6. 8. Peng Y, Ashfaq R, Ewing G, et al. False-positive sentinel lymph nodes in breast cancer patients caused by benign glandular inclusions: report of three cases and review of the literature. Am J Clin Pathol 2008; 130: 21–7. 9. Corben AD, Nehhozina T, Garg K, et al. Endosalpingiosis in axillary lymph nodes: a possible pitfall in the staging of patients with breast carcinoma. Am J Surg Pathol 2010; 34: 1211–6. 10. Stolnicu S, Preda O, Kinga S, et al. Florid, papillary endosalpingiosis of the axillary lymph nodes. Breast J 2011; 17: 268–72. 11. Sarode VR, Euhus D, Thompson M, et al. Atypical endosalpingiosis in axillary sentinel lymph node: a potential source of false-positive diagnosis of metastasis. Breast J 2011; 17: 672–3. 12. Salehi AH, Omeroglu G, Kanber Y, et al. Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma: a potential diagnostic pitfall. Int J Surg Pathol 2013; 21: 610–2.
667
13. Lakhani SR, Ellis IO, Schnitt SJ, et al. WHO Classification of Tumours of the Breast. 4th ed. Lyon: IARC, 2012; Chapter 7, Intraductal papillary lesions.
DOI: 10.1097/PAT.0000000000000173
Mammary analogue secretory carcinoma of minor salivary glands Sir, Mammary analogue secretory carcinoma (MASC) is a recently described distinctive salivary gland neoplasm with similar morphological and immunohistochemical attributes to secretory carcinoma (SC) of the breast.1 Prior to its description in 2010, MASC used to be regarded as one of a number of known benign and malignant salivary gland tumours.2,3 MASC is usually low grade but high grade transformation has recently been described.4 A case of MASC in the upper lip is presented and the differential diagnosis of this intriguing tumour is discussed. A 66-year-old man presented with a 6 month history of thickening associated with swelling on the inner surface of the upper lip. The swelling which was subject to accidental biting fluctuated in size. On examination, a mass which was thought to represent minor salivary gland tumour was found. The mass was excised and the patient is being clinically followed up with no evidence of disease recurrence. The resected specimen consisted of a mucosal covered piece of tissue 12 10 8 mm. The cut surface showed a partly cystic, brown, 10 mm nodule. An encapsulated partly cystic tumour was seen microscopically (Fig. 1A). The tumour was made up of eosinophilic cells with glandular areas and microcystic spaces (Fig. 1B,C). The central part of the tumour showed degeneration and necrosis (Fig. 1A). Haemosiderin deposition attributed to occasional accidental biting by the patient was seen in parts of the tumour. The tumour cells appeared ‘oncocytic’ with round to oval nuclei and granular eosinophilic cytoplasm (Fig. 1D,E). Mild nuclear atypia was seen but mitoses were very rare. Globular eosinophilic material was present in the cytoplasm of some of the tumour cells and slightly basophilic material was noted in most of the microcystic spaces (Fig. 1E). Neutral and acidic mucinous material was noted in a few cells. Most of the cells also showed periodic acid Schiff (PAS) positivity, accounting for the ‘oncocytic’ appearance in the routine sections. The adjacent minor salivary glands and the overlying surface epithelium were normal. The lines of excision were clear. The tumour cells were positive for gross cystic disease fluid protein 15 (GCDFP-15; Fig. 2A), S100 (Fig. 2B), mammaglobin A (Fig. 2C) and MUC4 (Fig. 2D). Carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), vimentin, P63, b-catenin and cyclin D1 were also positive. Oestrogen, progesterone, human epidermal growth factor 2 and epidermal growth factor 1 were not expressed. Cytokeratin 7 was positive but cytokeratin 20 was negative. The tumour had a low proliferative index with up to 5% of the cells expressing MIB-1. Therefore, the tumour showed all the attributes of MASC. MASC was previously most often diagnosed as adenocarcinoma NOS, acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), polymorphous low grade adenocarcinoma and cystadenocarcinoma or cystadenoma.2,3 Cystadenoma and
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
668
Pathology (2014), 46(7), December
CORRESPONDENCE
A
H&E ×1
B
H&E ×4
C
D
H&E ×40
E
H&E ×20
H&E ×60
Fig. 1 Histological and histochemical properties of the lesion. (A) Three cross sections of the tumour. The tumour is circumscribed with cystic change and eosinophilic luminal contents. (B) Part of an encapsulated lesion (right) and normal minor salivary glandular tissue (upper left). The tumour displays a microcystic growth pattern. (C) Higher magnification of the tumour showing eosinophilic (right) and slightly basophilic cells (left). (D,E) Large eosinophilic cells with pseudoglandular growth pattern. The cells have oval to spindle shaped mildly atypical nuclei. An eosinophilic globule is seen in an oval space (centre, E) and slightly basophilic material is present within other spaces.
ACC were the initial differential diagnoses in this case. Indeed, Williams and Chiosea estimate that as many as 8% of salivary cystadenomas may represent cases of MASC.5 The majority of cases in the initial report were located in the parotid gland.1 Subsequent reports have shown that while the parotid gland is the most common site of origin, MASC may also arise in the other major salivary glands and the oral cavity, including the lip, buccal mucosa and soft palate. MASC usually shows a number of growth patterns including cystic, tubular, solid or papillary architecture. Eosinophilic cytoplasm, intraluminal or intracytoplasmic colloid-like secretions that stain positive for PAS and are diastase resistant are usually seen.2,3 The morphological spectrum of MASC has grown to include tumours with both macrocystic and microcystic areas, intracystic papillary patterns and solid areas, and the morphological differential diagnosis of MASC may be broader than previously considered, especially on small biopsy material.3 Other tumour types that may show similar architectural patterns include polymorphous low grade adenocarcinoma and adenoid cystic carcinoma.4 Immunohistochemically MASC shows positivity with numerous antibodies; the most useful being mammaglobin, MUC4 and S100. Mammaglobin immunoreactivity has been found in 55% of all salivary gland tumours.6 Mammaglobin positivity alone is not diagnostic of MASC. MUC4 has been reported in >80% of cases of MASC.7 MUC4 has also
been shown to be positive in MEC and MUC4 positivity in MEC has been associated with increased risk of recurrence and death.7 The prognostic value of MUC4 in MASC is unclear. S100 is variably expressed in many salivary gland tumours, particularly those with a myoepithelial element. Co-expression of S100 with mammaglobin has been regarded as a very useful marker in identifying MASC.8 However, these markers have also been shown to be expressed by the morphological mimics of MASC.2 Most studies have detected a low proliferation index by Ki-67 staining with 5–28% of MASC tumour cells expressing this marker.4 This tumour also had a low proliferative index with not more than 5% of the tumour cells expressing MIB1. MASC usually presents as a slow-growing, painless mass in adults.3 The tumour in our patient, in line with the majority of previously described cases, was circumscribed and completely encapsulated. Poor circumscription, infiltrative growth or invasion has been noted in about one-quarter of the cases.5 MASC has an overall favourable outcome but like ACC and other low-grade salivary gland carcinomas, MASC does have the capacity to occasionally behave aggressively in the form of recurrences, regional lymph node metastases, and even disease-related deaths.4 Currently there is no way to definitively predict the behaviour of MSAC. This is largely because MASC is such a rare tumour, accounting for
