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Breast

Invasive breast carcinoma of no special type and variants

NST, rare variants

Last author update: 1 August 2012

Last staff update: 18 June 2024

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PubMed Search: Carcinoma with osteoclastic giant cells, Glycogen rich carcinoma breast , Lipid rich carcinoma breast, Sebaceous carcinoma breast, Signet ring cell breast

Table of Contents

Cite this page: Roychowdhury M. NST, rare variants. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastNSTrare.html. Accessed December 26th, 2024.

Choriocarcinomatous / pleomorphic patterns (pending)

Clear cell (pending)

Glycogen rich

Definition / general

Breast carcinoma in which at least 90% of the neoplastic cells have abundant clear cytoplasm due to glycogen
First described in 1981 (Cancer 1981;48:2003)
Rare, 1% - 3% of breast carcinomas
May be a variant of apocrine carcinoma

Radiology images

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Mammogram shows circumscribed mass

Prognostic factors

Prognosis similar to invasive ductal carcinoma (Am J Surg Pathol 1995;19:904)

Case reports

33 year old woman whose tumor had neuroendocrine features (Pathologica 2001;93:676)
45 year old woman with solid papillary tumor (J Clin Pathol 2003;56:552)
55 year old woman (Case Rep Oncol 2011;4:452)
59 year old woman (World J Surg Oncol 2008;6:44)
61 year old woman (Arch Med Lab Pathol 2003;127:1629)
Intraductal lipid rich carcinoma with component of glycogen rich carcinoma (J Breast Cancer 2012;15:135)

Gross images

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Solid papillary pattern within cystically dilated duct

Microscopic (histologic) description

Solid or solid / papillary patterns of large clear cells with distinct cell borders containing glycogen in 90% or more cells
Often associated with intraductal component of varied type
Often has apocrine features
Cells have clear to granular cytoplasm
May have scant intracellular mucin (Histopathology 1987;11:857)
No cytoplasmic vacuoles

Microscopic (histologic) images

AFIP images

PAS+ dark granules

Clear cells

Sheets of polygonal cells

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Ample clear cytoplasm

PAS positive

Abundant calcifications

Resembles renal clear cell carcinoma

Intraductal lipid rich carcinoma with component of glycogen rich carcinoma

CK8 / 18+

Polygonal cells

Cytology description

Hypercellular with tumor cells in loosely cohesive syncytial groups and some single cells
Most tumor cells have abundant, finely granular eosinophilic cytoplasm or foamy to clear cytoplasm with well defined cytoplasmic membranes and moderate / marked nuclear pleomorphism with central round/oval nuclei containing prominent nucleoli (Acta Cytol 2008;52:65)
PAS staining may be helpful (J Med Invest 2002;49:193)

Positive stains

PAS diastase sensitive (glycogen)

Negative stains

CK20, lipid stains (done on fresh / frozen tissue)

Electron microscopy description

Non membrane bound glycogen and empty glycogen lakes
Tight junctions between tumor cells, immature desmosomes, occasional short microvilli (Am J Surg Pathol 1986;10:553)

Differential diagnosis

Apocrine carcinoma
Clear cell sugar tumor:
- Positive for melanocytic markers (Am J Surg Pathol 2002;26:670)
Lipid rich carcinoma:
- Positive for lipid stains, negative for glycogen
Myoepithelial lesions
Secretory carcinoma:
- Younger patients, low grade histology

Additional references

Hum Pathol 1991;22:81

Lipid rich

Definition / general

90%+ cells have prominent intracytoplasmic neutral lipid

Clinical features

1% - 2% of breast carcinomas
Axillary metastases may resemble histiocytes

Prognostic factors

Poor prognosis due to frequent (70%) nodal metastases at presentation

Case reports

53 year old woman (Acta Chir Belg 2008;108:115)
55 year old man (Pathology 1995;27:280)
56 year old woman with focal chondroid metaplasia in tumor (Pathol Int 1998;48:912)
62 year old woman (Arch Pathol Lab Med 2003;127:e396)
78 year old woman with solid alveolar pattern in tumor (Breast Cancer 1998;5:171)

Gross description

Lobulated, variable circumscription, firm
1 to 15 cm

Microscopic (histologic) description

Nests, cords and sheets of large polygonal cells with foamy or vacuolated cytoplasm containing lipid
May resemble clear cells or lipoblasts
Irregular nuclei with coarse chromatin, moderate atypia, prominent nucleoli
Other patterns are large pleomorphic cells in alveolar pattern with hobnail appearance, oncocytic or apocrine type change

Microscopic (histologic) images

AFIP images

Polygonal tumor cells

Positive stains

Lipid stains (Sudan black, Oil red O on fresh tissue)
HER2 (71%+) (Tumori 2008;94:342, Ann Diagn Pathol 2011;15:225)

Negative stains

Glycogen (PAS)
Mucin
Usually ER, PR
CK5 / 6, CK14, p63

Electron microscopy description

Numerous intracytoplasmic non membrane bound lipid droplets, often within autophagocytic vacuoles
No evidence of lipid synthesis by rough ER or Golgi complexes (Virchows Arch A Pathol Anat Histopathol 1988;413:381)

Electron microscopy images

AFIP images

Luminal microvilli, lipid droplets and mitochondria

Differential diagnosis

Apocrine carcinoma:
- Uniformly granular and eosinophilic cytoplasm, GCDFP-15+, no lipid
Glycogen rich carcinoma:
- Clear cytoplasm, secretions are glycogen (PAS+), not lipid
Oncocytic carcinoma:
- Granular and markedly eosinophilic cytoplasm, no lipid
Secretory carcinoma:
- Low grade, PASd+ secretions, no lipid
Xanthogranulomatous mastitis (on core biopsy):
- Not invasive, cells are CD68+, alpha-1-antitrypsin+ histiocytes (Pathol Int 2009;59:234)

Oncocytic (pending)

Osteoclast

Definition / general

Part of WHO classification
Osteoclastic giant cells are present in stroma
Presence of giant cells does not alter prognosis

Case reports

44 year old and 83 year old women (Diagn Pathol 2010;23:55)
46 year old woman (Radiographics 2002;22:691)
51 year old woman with pleomorphic carcinoma and prominent osteoclastic giant cells (Pathol Int 2009;59:91)
Cases with neuroendocrine carcinoma (Pathologica 2008;100:176)

Gross description

Often brown due to vascular stroma with hemosiderin

Microscopic (histologic) description

Giant cells are associated with vascular stroma with extravasated red blood cells and hemosiderin, also chronic inflammatory cells and fibroblasts
Giant cells have variable size and variable numbers of nuclei
Similar histologic features in nodal metastases and recurrences (Arch Pathol Lab Med 1986;110:636)
Carcinoma component may be any type

Microscopic (histologic) images

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Invasive ductal carcinoma of the breast with osteoclast-like giant cells

Various images

Differentiated well cribriform carcinoma

Osteoclast-like giant cells in close contact to tumor cells

Cytology description

Abundant giant cells and mononucleated stromal cells associated with carcinoma cells (Diagn Cytopathol 2005;33:246)

Positive stains

Osteoclastic giant cells: CD68; also acid phosphatase, lysosome, nonspecific esterase; also MMP9, TRAP, cathepsin K

Negative stains

Osteoclastic giant cells: S100, actin, keratin, EMA, ER, PR, alkaline phosphatase

Electron microscopy description

Osteoclasts are histiocytes

Additional references

Ann Pathol 1989;9:189, Hum Pathol 1990;21:1142

Sebaceous

Definition / general

Very rare primary breast carcinoma resembling skin adnexal tumor with sebaceous differentiation, but no evidence of cutaneous derivation (see J Med Case Rep 2008;2:276 for cutaneous tumor of breast)

Clinical features

Associated with Muir-Torre syndrome (Cancer 2005;103:1018)

Case reports

45 year old woman with extensive metastatic disease (Pathol Int 2000;50:63)
46 year old woman with Muir-Torre syndrome (AJR Am J Roentgenol 2000;174:541)
50 year old woman (Pathol Int 2009;59:188)
63 year old woman (Virchows Arch 2006;449:484)
83 year old woman with tumor of nipple (J Cutan Pathol 2008;35:608)

Microscopic (histologic) description

Well defined solid sheets or lobules of atypical epithelial cells, including large, pale or clear cells with coarsely vacuolated cytoplasm, containing Oil red O staining lipid and often scalloped nuclei
Often focal squamous morules

Microscopic (histologic) images

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Skin

Positive stains

Cytokeratin, including 35betaH11, EMA (Pathol Res Pract 1993;189:888)
ER, PR, Oil Red O
Mismatch repair genes: MLH1, PMS2, MSH2, MSH6 (Ceska Gynekol 2010;75:50)
Some cells may express neuroendocrine markers

Negative stains

GCDFP-15, CEA, S100 and vimentin
Alpha smooth muscle actin, p63, androgen receptor (usually), mucins, HER2 and CK15

Electron microscopy description

Empty appearing, non membrane bound vacuoles

Differential diagnosis

Apocrine carcinoma:
- > 90% of tumor cells have cytologic or immunohistochemical features of apocrine cells
Lipid rich carcinoma:
- Usually not coarsely vacuolated, often squamous morules, usually HER2+, ER-, PR-

Signet ring cell

Definition / general

Ductal carcinoma with cells resembling gastric carcinoma due to acidic mucin that fills cytoplasm and displaces nucleus
Excludes cases with lobular features (signet ring cell variant of lobular carcinoma)

Case reports

40 year old woman with signet ring cell carcinoma of the breast as a source of pelvic floor metastatic mass (Acta Chir Belg 2005;105:224)
52 year old woman with signet ring cell carcinoma associated with invasive ductal carcinoma (Breast Cancer 1999;6:223)
54 year old woman with signet ring cell carcinoma of the breast with uterine metastasis (J Obstet Gynaecol Res 2012;38:948)
68 year old woman with signet ring cell carcinoma of the breast (Pathol Int 2000;50:67)
73 year old woman with invasive ductal carcinoma of the breast with signet ring cell and mucinous carcinoma components (Diagn Cytopathol 2007;35:171)
74 year old woman with metastatic breast cancer to the stomach (Case Rep Oncol 2010;3:142)
Ductal type signet ring cell carcinoma of breast (Pathology 2011;43:282)

Microscopic (histologic) description

Mucin fills cytoplasm and displaces nucleus
Usually coexists with invasive ductal NOS
High nuclear grade; DCIS may be present, but no lobular features (by definition)

Microscopic (histologic) images

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Breast metastasis to stomach

Cytology description

Look for signet ring cells if plasmacytoid cells are identified
Favor ductal carcinoma if hypercellular, single signet ring cells, high nuclear grade and tubule formation
Favor lobular carcinoma if hypocellular, single signet ring cells and mild / moderate nuclear grade (Cytopathology 2009;20:321)

Differential diagnosis

Metastatic GI signet ring cell carcinoma:
- History, no DCIS, CDX2+ and ER- (Am J Clin Pathol 2004;121:884, ISRN Obstet Gynecol 2011;2011:426150)
Signet ring cell variant of lobular carcinoma:
- Usually classic lobular component present, no DCIS, ER+ and E-cadherin negative

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