57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 1
Case Discussion
Chandandeep Nagi, MDAssociate Professor
Baylor College of Medicine
Houston Society of Clinical Pathologists Symposium
Clinical Presentation
• 66 y.o woman with hypothyroidism (s/p thyroidectomy), obesity, depression
• Screening mammogram– new 1.6cm mass at left 1 o’clock
• Add mammo, u/s, MRI– circumscribed, lobulated mass– suspicious with no other lesions
• No nipple inversion, discharge or skin involvement, pain
• Prominent LN’s in the left axilla
Clinical Presentation
• No sig PMH• PSxH
– Thyroidectomy (80’s), hernia repair, C‐section (remote)
• Gen Ros:– No fever, chills, sweats, no back pain, bone pain, headaches,
dizziness, weakness, or fatigue
• HEENT: Negative• CV: Negative• Resp: Negative• GI: Negative • GU: Negative• Muscloskeletal: Negative
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 2
10/20/15 Screening mammogram
There is a new 1.7 cm mass with an indistinct margin and a few associated calcifications in the left breast at 1 o'clock middle depth.
10/30/15 Left Breast Diagnostic Mammogram
There is a new 1.7 cm oval mass with a circumscribed margin in the left breast at 1 o'clock middle depth. An ultrasound is recommended.
10/30/15 Left Breast Ultrasound
There is a 1.6 cm x 1.5 cm x 1.1 cm hypoechoic lobulated mass with a microlobulated margin in the left breast at 1 o'clock middle depth.
Color flow imaging demonstrates that there is vascularity present.
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 3
U/S guided core biopsy
U/S guided core biopsy
U/S guided core biopsy
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 4
U/S guided core biopsy
CK 5/6 CK 17
U/S guided core biopsy
ER CD117CD117
Lumpectomy
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 5
Lumpectomy
Lumpectomy
Diagnosis
• Infiltrating Adenoid Cystic Carcinoma
– Solid type
– 2.0cm
– High mitotic rate
– No LVI
– Triple Negative with basal CK and CD117 positivity
• Negative Margins
• Negative Nodes
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 6
ACC ‐ Epidemiology
Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. WHO Classification of Tumors of the Breast. Vol. 4. France: IARC; 2012SEER Stat Fact Sheets: Breast. Bethesda: National Cancer Institute.
ACC ‐ Epidemiology
SEER Stat Fact Sheets: Breast. Bethesda: National Cancer Institute.Ghabach B. et al. Breast Cancer Research 2010 12:R54
ACC ‐ Epidemiology
• Uncommon, less than 0.1%– Most small, recent larger cohorts
• Geschickter et al, 1945
• Age– 33 to 97 with mean of 60/63
• No change in incidence rate– Lower in African‐Americans
• Mostly solitary lesions
• Occasional cases in males
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 7
Clinical Presentation
• Most often palpable– Circumscribed and/or lobulated– Below nipple (up to 50%)– May be painful
• Unlike salivary not correlated with perineural
• Mammographic– Irregular or lobular mass– Subtle architectural distortion
• U/S– Irregular shaped– Hypoechoic or heterogeneous– Parallel to skin lines, no halo or posterior shadowing
• MRI– Lobulated or irregular masses– Enhancement – rapid and heterogeneous
Mammography
Glazebrook KN et al. AJR:194, May 2010 (1391‐6)
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 8
Gross Features
• Firm, white
– Occasional microcysts
• Circumscribed or ill‐defined
• May have minimal stromal response
• Mean size is 3cm (0.5 to 12cm)
Histology
• Similar to counterparts in salivary gland
• Morphologically heterogeneous
• Dual cell population of luminal and myoepithelial/basal cells in 3 patterns
– Cribriform
– Reticular (trabecular)‐tubular
– Solid
• True glandular spaces and pseudolumina
Histology
• Luminal cells form solid nests or small lumens– May be empty or filled with secretions
– Cells are cuboidal to spindle shaped
• Myoepithelial/basal cells can form large cribriform spaces– Lined by myoepithelial type cells
• Scant cytoplasm, round to oval nuclei
– Filled with basement membrane type material
– Collagenous, myxoid, mucinous
• Squamous and/or sebaceous metaplasia
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 9
Histology
Histology
Histology
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 10
Grading
• Nottingham histologic grading system
• Others
– Proportion of solid growth
• No solid elements (grade I)
• <30% (grade II)
• >30% (grade III)
• Unclear about predicting prognosis
• Possibly helpful in treatment
IHC
• Luminal type cells– Positive for CK7, Cam5.2, C‐Kit (CD117), EMA
– Usually negative for ER, PR, Her2
• Myoepithelial type cells– positive for p63, SMA, CK5/6 (basal), laminin
• Low Ki‐67 rates– Higher in higher grade; unclear if related to outcome
• Triple negative breast cancers with basal like features
IHC
ER CD117
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 11
IHC
CD117 CD117
Association / genesis
• Microglandular adenosis• Tubular adenosis• Medullar carcinoma
– Basal like transcriptome– Higher frequency of alterations
• Insitu component• Adenomyoepithelioma• Metaplastic carcinoma / adenosquamous
– Immunohistochemical similarities– Higher frequency of alterations
Molecular / Cytogenetics
• t(6;9)(q22‐23;p23‐24)– Fusion between oncogene MYB and trnascription factor NFIB– In most (>90%)
• Fewer abberations compared to other basal like• Less aneuploidy• Normal BRCA1 gene function• ?stem cell like properties• ERalpha36
– MAPK/ERK– EGFR
• SOX10, IMP3
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 12
DDX
• Infiltrating cribriform carcinoma– Empty or filled with secretory material– Almost all positive for ER, PR– No myoepithelial like cells
• DCIS , cribriform type– Myoepithelial cells at periphery– Almost all ER/PR positive
• Collagenous spherulosis– Fenestrated appearance– Eosinophilic fibrillar and/or hyaline spherules of basement membrane
like material (positive PAS and alcian blue)– Inner myoepithelial outer luminal cells
• Adenomyoepithelial Carcinoma• Cylindroma
Prognosis / Rx
• Excellent prognosis– 90% – 100% survival at 10 yrs
– Local recurrence : 6%
– Axillary LN metastasis : 3%
– Distant metastasis and death : 3%• Lung; bone, liver, brain, kidney
• Usually breast conservation surgery– Chemo controversial
– Radiotherapy may help
– LN +/‐
57th Annual HSCP Spring Symposium 4/16/16
Chandandeep Nagi, MD 13
Summary
• Triple negative with good prognosis
• Score as poor prognosis using 21 gene recurrence score or 70 gene profile score
– Histology more important than Molecular
• Important not to miss
THAT’S ALL FOLKS
ANY QUESTIONS ?