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Metastasis of Mixed Mucinous Carcinoma of Breast to Axillary Lymph Node
Sangeeta B Kulkarni (Bhide)*, Kanchanmala G Ghorpade**, Ila M Vora***, Shanu Srivastava+
 

Abstract
Mucinous carcinomas of breast constitute 1.5 – 5% of all primary breast carcinoma. They occur in older and postmenopausal women. They are classified as pure mucinous carcinoma and ‘impure’ or mixed mucinous carcinomas.

Mixed mucinous carcinoma of breast are those where mucinous areas are admixed with invasive carcinoma and carry unfavourable prognosis as compared to pure mucinous carcinoma. Moreover metastasis to axillary lymph node is rare in pure mucinous carcinoma (2 – 4%).
Hence a search of invasive areas, which are, usually invasive ductal carcinoma should be made in all lymph nodes showing metastasis of mucinous carcinoma.

We present here a case of mixed mucinous carcinoma of a breast with metastasis in right axillary lymph node. The clinical presentation, characteristic histopathological features and prognostic factors are highlighted.

 

Introduction
Mammary mucinous carcinomas are known as colloid, mucoid or gelatinous carcinomas and constitute 1.5 – 5% of all primary breast carcinomas.1-4 They occur in older, postmenopausal women.1,3,5

Mucinous carcinoma is described as carcinoma composed of rich extra cellular mucin in which tumour cells float as separate groups.1,3,5
These carcinomas may be mixed with invasive ductal carcinoma (IDC) known as impure or mixed mucinous carcinoma and the prognosis depends upon the predominant component.

This case is presented to highlight clinical features, characteristic histopathological appearance and prognostic factors.

Case Report

Fifty year old female presented with a complaint of a lump in the right axilla.

An excisional biopsy was done.

A single, oval well-circumscribed tumour mass measuring 6 x 4.5 x 2.5 cm was received. External surface showed areas of haemorrhages. Cut section showed soft, glistening, grey-white coloured, gelatinous ‘current-jelly’ like mass measuring 4 x 3 cm with pushing margins. At the periphery, it was solid grey-white, probably lymph node (Fig. 1).

Microscopic Examination
Section from lump showed very little identifiable lymph node at the periphery. It was totally replaced by scattered islands of uniform round tumour cells having little pleomorphism and low mitotic activity. The cells were suspended in pools of extracellular mucinous material and surrounded by bands of fibrous connective tissue. These tumour islands were arranged in solid clusters and acinar pattern at places, suggesting mucinous carcinoma (Fig. 2). Alcian blue stain for mucin was positive.

On further study, we could reveal an area of IDC showing tumour cells arranged in solid nests and cords. They were large, pleomorphic having abundant eosinophilic cytoplasm and centrally placed nuclei with prominent nucleoli and mitotic activity. There was infiltration of tumour in fibrous stroma without being surrounded by mucin (Fig. 3). Chronic inflammatory cells and few multinucleate giant cells were seen in the stroma.

Diagnosis was considered as metastasis of mixed mucinous carcinoma in to right axillary lymph node. Mammography was suggested. It showed a lump in right breast.

Fig. 1 : Cut surface showing glistening gelatinous tumour with pushing margins and solid grey-white area at the periphery. Fig. 2 : Photomicrograph of mucinous carcinoma showing scattered islands of tumour cells floating in lakes of mucin and delicate fibrous septa. (H and E – 100X).

Fig. 3 : Photomicrograph showing a focus of infiltrating ductal carcinoma in lymph node. (H and E – 100X).

Discussion
Although mucinous carcinoma (MC) of the breast is considered to originate from ductal carcinoma, it is not known whether mucinous growth begins in the intraductal carcinoma or later in invasive carcinoma.6 The study by Kanto et al showed that mucinous growth can begin in the intraductal carcinoma and in IDC.6
This occurs in older, postmenopausal women.1,3,5 The mean age of MC is higher than IDC.2,4

Clinically MC presents as soft, palpable mass.3

Mucinous carcinomas are classified as pure MC (PMC) and mixed type (MMC).4,5,7,8 In both at least 1/3rd of surface area of tumour sections examined consists of mucin.2,7,8

According to Rasmussen et al all mucinous carcinomas originate as pure carcinoma and a clone of tumour cells differentiate and lose its ability to produce and secrete mucin. The tumour would change from pure MC to MMC.2 This explains larger size of MMC than pure MC.2 Usually average size of MC is 2-3 cm whereas MMC are larger.2,3

Classic and often quoted description of MC on microscopy is “Small clusters of tumour cells” floating in sea of mucin.1-3,5 Whereas MMC shows solid elements which are invasive ductal or lobular, papillary, adenocystic, tubular or a combination of these.7

In this case patient presented with lump in the right axilla. On histopathology all sections showed metastasis of MC in lymph node. However, pure MC rarely metastasizes to lymph node. Therefore more sections were submitted to identify other components within the tumour. Subsequently IDC component was identified which has changed the diagnosis as well as prognosis.

There are differences in mammographic appearance of pure MC and MMC that have a histologic basis. The important differences are shown in Table 1.

The biologic behaviour of this tumour is determined by presence of non mucinous areas rather than mucin.2 MC have better prognosis than IDC but pure MC are less aggressive than IDC and MMC.4,5

Pure mucinous carcinoma is partially or entirely a form of in situ carcinoma in which some component of mucin secretion detaches the epithelium from underlying stroma, breaks it up and engulfs it and mucin is seen towards the base of the cell. Thus it is the mucin rather than tumour cells that are invading the stroma.5 This explains extracelluar mucin in pure MC and its excellent prognosis.5

The mucin is acidic- Sulphomucin or neutral type demonstrated by alcian blue or PAS stain.1,10

The differential diagnosis for MC are as follows.1,3,5,11

  1. Signet ring carcinoma where mucin is intracytoplasmic.
  2. Mucocoele like lesions which are reactive in nature. They can be identified on microscopy by few cell islands with myoepithelial cells in mucin pools seen at periphery rather than centrally. Variably distended ducts due to mucinous material are seen.

As these lesions are associated with atypical ductal hyperplasia, ductal carcinoma in situ or MC, thorough sampling is required.



Conclusion
Prognostic factors for MC are type of MC, tumour size, cellularity and lymph node status.

Thorough sampling is required to differentiate types of MC and mucocoele like lesions.

Search for invasive carcinoma in all lymph node biopsies showing metastasis of MC is mandatory to determine the prognosis.

References

  1. Hanby AM, Millis RR, Oberman HA. The breast. In: sternberg SS, Antonioli DA, Carter D, Mills SE, Oberman HA editors. Diagnostic surgical Pathology. 3rd edn, Vol 1. Philadelphia: Lippincott Williams and Wilkins, 1999; 319-85.
  2. Rasmussen BB, Rose C, Christensen B. Prognostic factors in primary mucinous breast carcinoma. Am J Clin Pathol 1987; 87 : 155-60.
  3. Sharkey FE, CraigAllred D, Valente PT. Breast. In: Damjanov I, Linder J editors. Anderson’s Pathology. 10th ed Vol. II. St. Louis: Mosby year book, Inc, 1996; 2354-85.
  4. Toikkanen S, Kujari H. Pure and mixed mucinous carcinoma of the breast: A clinicopathologic analysis of 61 cases with long term followup. Hum Pathol 1989; 20 : 758-64.
  5. Rosai J. Breast. In: Rosai J, editor. Ackerman’s surgical pathology. 8th edn, Vol II. . U. S. A. Mosby year book, Inc, 1996; 1565-1660.
  6. Kato N, Endo Y, Tamura G, Katayama Y, Motoyama T. Mucinous carcinoma of the breast: a multifaceted study with special reference to histogenesis and neuroendocrine differentiation. Pathol Int 1999; 49 (11) : 947-55.
  7. Coady AT, Shousha S, Dawson PM, Moss M, James KR, Bull TB. Mucinous carcinoma of the breast: Further characterization of its three subtypes. Histopathology 1989; 15 : 617-26.
  8. Rasmussen BB. Human mucinous breast carcinomas and their lymph node metastases: A histological review of 247 cases. Pathol Res Pract 1985; 180 (4) : 377-82.
  9. Wilson TE, Helive MA, Oberman HA, Joyant LK. Pure and mixed mucinous carcinoma of the breast: Pathologic basis for differences in Mammographic appearance AJR Am J Roentgenol 1995; 165 (2) : 258-89.
  10. Andre S, Cunha F, Bernardo M, Meneses SJ, Cortez F, Soares J. Mucinous carcinoma of breast - A pathological study of 82 cases. J Surg Oncology 1995; 58 (3) : 162-7.
  11. Chinyama CN, Davies JD. Mammary mucinous lesions: congeners, prevalence and important pathological associations. Histopathology 1996; 29: 533-39.
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*Assoc Professor; **Professor and HOD; ***Professor; +Lecturer; Department of Pathology, Terna Medical College, Nerul. Navi Mumbai – 400706. 
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