False positive diagnosis in breast FNAC.

Some common lesion leading to false positive diagnosis in FNA of breast are listed with Keys to differentiate them.
Artifactual Atypia
Most common of these is disruption of cell aggregates by too vigorous smearing, which can mimic the loss of cohesion characteristic of malignant epithelial cells .
Excessive smearing pressure can also cause smudging of nuclei, giving a false impression of nuclear enlargement and pleomorphism.
Dying artifacts in alcohol-fixed Pap smears have a similar effect.

Hormonal Stimulation and Physiologic :Hyperplasia in Pregnancy and Lactation
Physiologic hyperplasia of acinar epithelial cells in late pregnancy and lactation can look worrying in FNA smears.
Key: The recognition of milky secretion is the main clue to a correct diagnosis to be correlated with clinical information.

Reactive Atypia
This is seen in mastitis fat necrosis, postoperative repair, and post radiation.
Key: Correct clinical information is important. A history of previous tissue injury and the presence of acute inflammatory cells (not just lymphocytes) rarely seen in breast cancer call for caution and careful evaluation of the nuclear structure of atypical cells.

Epithelial atypia, most likely hormone related, can be prominent in smears of fibroadenoma. This is the most frequent cause of false positive diagnosis in breast FNA.
Key: In most cases, the atypical cells constitute only a minor part of the cell population. The presence of benign components is a safeguard against an erroneous malignant diagnosis.

Papillary Lesions
The combination of high cellularity, loss of cell cohesion, and variable nuclear atypia sometimes seen in smears from benign papillary lesions may raise a suspicion of malignancy. A false positive diagnosis is possible, particularly if a papillary microarchitecture is notidentified.
Key: In general, the presence of background apocrine cells, foam cells, and single bipolar nuclei suggest a benign papilloma.
1. Franze´n S, Zajicek J. Aspiration biopsy in diagnosis of palpable lesions of the breast. Acta Radiol. 1968;7:241–262.
2. Zajdela A, Ghossein NA, Pilleron JP, et al. The value of aspiration cytology in the diagnosis of breast cancer: experience at the Foundation Curie. Cancer. 1975;35:499–506.
3. Greenberg M. Diagnostic pitfalls in the cytological interpretation of breast cancer. Pathology. 1996;28:113–121.


Anshu said...

This is true that false atypia can be quite worrisome, but in cases where dilemma is not resolvd, what should be the followup investigation protocol??

priya jyoti shrivastava said...

Very useful & practical information

Anonymous said...

did you encounter epithelial malignancy (DCIS/Invasive ductal carcinoma)in a case of phyllodes tumor?

Dr.Prashant Jani said...

Yes, I have encountered cases of frbroadenoma with DCIS.
Howevere they are not very common.
Common things first!!!


Anshu said...

i am posting a dilemma that i encountered recently. although not related exactly to this current topic. i got a case of fibroblastic lesion on anterior abdominal wall of a 40 yr old male. it was recurrent and m/s 5.0 cm in diameter. though cells were uniform looking but in focal areas there was high mitotic activity amounting to 3-4 MF/ hpf. how can we separate a desmoid from fibrosarcoma in this case, without IHC? what should be the other features which should be looked. in such cases what should be the comment in report.

Dr.Prashant A.Jani M.D.FRCPC said...

Dear Dr.Anshu,

Thanks for your email.

At Low power :

Fibrosarcoma will show spindle cells arranged in fascicles that intersect each other at acute straight angles with a herringbone appearance
Fibromatosis will show Longitudinally oriented fascicles of spindle cells in a prominent collagenous background, with a infiltrative growth pattern Thick walled vessels and a perivascular lymphocytic infiltrate may be seen

On High Power :
Fibrosarcoma : Mitotic activity is generally present, but variable Spindle cells resemble fibroblasts, with hyperchromatic nuclei Less differentiated tumors may have more hyperchromasia and foci of round cells but pleomorphism and numerous giants cells favor a diagnosis of MFH Fibromatosis :Spindle cells are benign-looking, with oval nuclei and one or more nucleoli with low mitotic activity

Dr.Prashant A.Jani M.D.FRCPC said...

Anshu has left a new comment on your post "False positive diagnosis in breast FNAC.":

This is true that false atypia can be quite worrisome, but in cases where dilemma is not resolvd, what should be the followup investigation protocol??

Dear Dr. Anshu,

The protocol for unresolved FNA with worrisome features is as follows;
1) Review the clinical history and radiological findings carefully.
2) review slides with a colleague
3) Examine cell block of the remaining cells in the FNAC container.
4) Recommend biopsy for definitive diagnosis.

I hope this helps you.
Keep well.

Dr.Prashant A. Jani.

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cosmetic surgery perth said...

We could stand to gather a second or even a third opinion over this one. I have read cases wherein this happens to women who had undergone breast implantation procedure.

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Interesting Case

Clinical History:

53 years male,History of hypertension and tachycardia,MRI abdomen:-Left adrenal mass:- size 5.8 cm Right renal mass:- size-3.0cm Microscopic examination of the renal mass showed vascular tumor with diffuse sheets of clear cells having Fuhrman grade III nuclei. There was no evidence of necrosis within the tumor. There was no evidence of extraparenchymal invasion.
Gross examination of the left adrenal gland revealed cortically centered, solid and multinodular mass measuring 6.5 x 6.0 x 5.0 cm and weighing 122 grams. The tumor was encapsulated but showed evidence of extraparenchymal penetration. The tumor had golden brown cut surface with areas of hemorrhage and necrosis. The partial nephrectomy showed 3.0cm x 3.0cm x 3.0 cm yellow solid mass which did not invade into the perinephric adipose tissue.
Microscopically, the adrenal mass had predominant diffuse sheets and focal trabecular arrangements. The former pattern was present in about third of tumor. The cells had clear cytoplasm and round to ovoid nuclei with conspicuous nucleoli. Mitotic rate was 9/50 HPF and included atypical forms. Gross necrosis and capsular invasion were documented microscopically. There was no evidence of lymphovascular invasion. Considering the above mentioned features, a Weiss histopathologic score2 of 7/9 was applied.


The differential diagnosis included Renal Cell Carcinoma (RCC) with contralateral adrenal metastasis, Adrenocortical carcinoma (ACC) with contralateral renal metastasis, synchronous RCC and ACC or synchronous RCC and adrenocortical adenoma. A panel of immunohistochemical stains was performed to sort out the diagnosis. Adrenal tumor demonstrated strong Vimentin positivity and is negative for CK7, CK20, E1/AE3, EMA, Synaptophysin and S100.Renal cell carcinoma was positive for CK7, AE1/AE3, EMA (weak) and Vimentin. It was negative for CK20, Synaptophysin and S100. The difference of immunoprofile between the two tumors documented that they originated from two different primaries.

Final Diagnosis:

The diagnosis of synchronous RCC and ACC rather than metastasis influences the prognosis.


The longest disease free interval after removal of contralateral adrenal metastasis was 12.1 years8 and the longest crude survival was 14.3 years. In contrast non metastazing RCC has an excellent prognosis if no metastasis developed.