Histopathology 1978, 2, 171-176

Primary signet ring cell carcinoma of the breast

M.HARRIS,* S.WELLS & K.S.VASUDEV Department of Pathology, Withington Hospital, Nell Lane, Manchester M20 8LR Accepted for publication 23 November 1977 HARRISM., WELLS S. & VASUDEV K.S.(1978) Histopathology z, 171-176

Primary signet ring cell carcinoma of the breast Three examples of primary signet ring cell carcinoma of the breast are described. This form of breast carcinoma deserves recognition as an entity because its prognosis may differ from colloid carcinoma of the breast and because of potential difficulty in distinguishing it from metastatic carcinoma. Key words: pimary mammary carcinoma, signet ring cell carcinoma

Introduction Although mucoid or colloid carcinoma with its abundance of extra-cellular mucin is a well-known form of breast carcinoma, accounting for 0.8-3.8% of all such tumours (Harris 1977), its signet ring variant is little recognized. We report on three examples of this tumour in an attempt to familiarize pathologists with it. We suggest that it deserves recognition as a sub-group of mucoid carcinoma in the classification of breast cancer because it may present problems in diagnosis to those who are unaware of its existence and because it may have a different prognosis to the classical mucoid carcinoma.

Clinical data and macroscopic appearances The clinical data for the three cases is summarized in Table macroscopic pathological features.

I,

together with the main

*Address correspondence to Dr M.Harris 0309-0167/78/0500-0171 $02.00 B

0 1978 Blackwell Scientific Publications.

Lower inner

Left

66

80

2

3

3 weeks

Central

Right

IZ months

60

I

Upper outer

Right

3months

Age

no.

Quadrant

Side

Length of history

case

Table I. Clinical data and pathological features

2.2 cm

Hard, grey

Hard

cm

11

Grey, mucoid

surface

Cut

1.5 cm

Tumour size

Welldefined

?

+

N o recurrence at 6 months

Follow-up

+

No recurrence at 10 months

No biopsy No recurrence at 3 months

Well-

+

No biopsy

+

Margins

defined

Lymph node metastasis

Peau d'orange

Y

N

4

Mammary signet ring cell carcinoma

173

Figure I. Case 3 . Carcinoma cells in which the cytoplasm is laden with mucin and the nucleus is displaced to one pole of the cell (signet ring cells). H & E. x 260. Figure 2. Case I . Sheets of signet ring cells with thin walled blood vessels but no other stroma. H & E . x162. Figure 3. Case 3 . Strands and clumps of signet ring cells with a moderate amount of fibrous stroma. H & E. x162. Figure 4. Case 3 . Intraductal carcinoma within the infiltrating signet ring cell carcinoma. Signet ring cells are seen in the intraductal lesion. H & E. x 162.

Microscopic features The tumours consisted of sheets and clusters of large, rounded cells with abundant granular cytoplasm which was faintly basophilic. Nuclei were usually compressed and displaced to one side of the cell to give a typical signet ring morphology (Figure I). In Case I , the tumour cells formed very compact groups and there was very little fibrous stroma (Figure 2), but in the other two cases a moderate amount of fibrous stroma

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M .Harris, S. Wells and K.S. Vasudev

was present between the clumps of cells (Figure 3). In no case was there any excess of extracellular mucin. In Cases 2 and 3 in-situ intraductal lesions were present; the intraductal tumour cells had a similar signet ring morphology to the invasive cells (Figure 4).However, in Case I , no in-situ lesions were found and, as will be discussed later, this led to difficulty in diagnosis.

Mucin stains The stains employed were Southgate’s mucicarmine, diastase-PAS, alcian blue/ diastase-PAS (AB/diastase-PAS), aldehyde fuchsin/alcian blue (AF/AB), and alcian blue/PAS (AB/PAS) following sulphuric acid hydrolysis (Cook 1972). The results are summarized in Table 2 where the findings in the signet ring cell carcinomas are compared with those obtained in four typical mucoid carcinomas of the breast. The staining reactions of themucin in the two tumour types is essentially similar, except that two of the three signet ring cell carcinomas contained sulphated mucin and one contained sialic acid. The findings in the typical mucoid carcinomas were in general agreement with those of Cooper (1974), the only difference being that he obtained a positive result for the presence of sialic acid using a sialidase digestion method. Table 2. Mucin staining reactions of signet ring cell carcinoma compared with typical mucoid carcinoma of the breast

Stain

Carcinoma of breast: Mucin demonstrated signet ring cell typical mucoid

Diastase-PAS

non-specific neutral

ABIdiastase-PAS

acid neutral

+ + +

AF/AB

suIphated

k

-

H2S04-AB/PAS

sialic acid

5

-

Southgate’s mucicarmine

non-specific

+

+

t

+ +

+ :all cases positive; k :some cases positive; - :all cases negative. Discussion Saphir (1941) described three examples of primary signet ring cell carcinoma of the breast in detail and there is passing reference to it in a number of standard textbooks of tumour pathology (Willis 1960, Evans 1966, Ackerman & Rosai 1974) but despite

Mammary signet ring cell carcinoma

175

this it does not receive recognition as an entity in modern classifications of breast cancer. The WHO classification of breast cancer (Scarff & Torloni 1968) makes no mention of signet ring cell carcinoma, and McDivitt, Stewart & Berg (1968) use the term synonymously with mucoid carcinoma, despite the obvious profound difference in the histological appearances of the two tumour types. Steinbrecher & Silverberg (1976) have used the term ‘signet ring cell carcinoma’ to describe a variant of lobular carcinoma of the breast-a nomenclature with which we disagree. These observations, combined with the results of enquiries amongst our colleagues, lead us to believe that this form of breast carcinoma is rarely recognized by modern pathologists. We feel that this is unsatisfactory for two main reasons. First, it is possible that the prognosis of signet ring cell carcinoma is poor in contrast with the good prognosis usually attributed to typical mucoid carcinoma (McDivitt, Stewart & Berg 1968). This suggestion was put forward by Saphir (1941)on the basis of the findings of his three cases. Follow-up of our own cases is too short and they are too few to allow comment on this point, but we feel that an attempt should be made to resolve the issue by identifying and following a sufficiently large series to produce a statistically significant result. Second, difficulty may arise in histological diagnosis when the pathologist is unaware of the existence of this entity. In our first case, where no intraductal lesions were present, the initial pathological diagnosis was ‘signet ring cell carcinomaprobably metastatic’. Follow-up and investigations, particularly of the alimentary tract, have failed to reveal a primary tumour elsewhere and oestrogen receptors have been detected in the tumour tissue; we now therefore believe that this is a primary breast tumour. The initial suggestion that it was probably a metastasis led to inadequate surgical treatment by local excision only. If, as in our Cases 2 and 3, intraductal carcinoma can be found the diagnostic problem is resolved and it is therefore worthwhile examining many blocks in breast tumours of this pattern to find in-situ lesions. In an attempt to estimate the frequency of unrecognized signet ring cell carcinoma of the breast we examined haematoxylin and eosin sections from IOO consecutive breast tumours which had been classified as infiltrating duct carcinoma. All tumours where the routine sections showed cytological features similar to those already described were further examined by mucin stains (Southgate’s mucicarmine and Alcian blue/PAS). In this way, one case of pure signet ring cell carcinoma was found (Case 3 in this report) and two further cases where small zones of the tumour had a signet ring pattern were also found. Thus, in our material pure signet ring cell carcinoma accounts for approximately I % of breast carcinomas but, despite its rarity, we believe it is a tumour which merits greater recognition than it currently receives.

References ACKERMAN L.V. & ROSAIJ. (1974) SurgicalPathology, 5th Ed., p. 921. C. V. Mosby, St Louis COOKH.C. (1972) Human Tissue Mucins, p. 4. Butterworths, London. COOPER D.J. (1974) Much histochemistry of mucous carcinomas of the breast and colon and nonneoplastic breast epithelium. Journal of Clinical Pathology 27, 3 I 1-3 14

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EVANS R.W. (1966) Histological Appearances of Tumours, 2nd Ed., p. 837. Livingstone, Edinburgh HARRIS M. (1977) Carcinoma of the female breast in Jamaica. Tropical and Geographical Medicine 299 74-83 MCDIVITT R.W., STEWART F.W. & BERGJ.W. (1968) Tumours of the breast. Atlas of Tumour Pathology, Second Series, Fascicle 2. Armed Forces Institute of Pathology, Washington DC SAPHIR0. (1941) Mucinous carcinoma of the breast. Surgery, Gynecology and Obstetrics 72, 9089 14 SCARFFR.W. & TORLONIH. (1968) Histological Typing of Breast Tumours, IHCT No. 2. World Health Organization, Geneva STEINBRECHER J.S. & SILVERBERG S.G. (1976) Signet-ring cell carcinoma of the breast. The mucinous variant of infiltrating lobular carcinoma? Cancer 37, 828-840 WILLISR.A. (1960) Pathology of Tumours, 3rd Ed., pp. 238 & 240. Butterworths, London