Yokohama system cytology

IAC CLassification Of breast malignancy the yokohama system

1. IAC Classification Of Breast Malignancy- The YOKOHAMA SYSTEM Presented By: Dr. Ritika Hooda BPS GMC(W ) Sonepat

2. The International Academy of Cytology (IAC) System for Reporting Breast Fine-Needle Aspiration Cytology (FNAC) has been developed following an initial meeting at the Yokohama International Congress of Cytology in 2016 , by a group of cytopathologists , radiologists, surgeons and oncologists expert in the management of breast lesions .

3. In the developing world, breast FNAC is still one of the most common procedures and is increasingly used as a key element in the screening campaign to reduce breast cancer mortality rates.

4. Advantages of breast FNAC Rapid, accurate and highly cost-effective diagnostic procedure with a minimal complication rate for the broad spectrum of benign and malignant breast lesions. High sensitivity in the range of 90–95% and a high positive predictive value (PPV) approaching 100% for the diagnosis of breast carcinoma.

5. Triple test Comprises of CLINICAL, IMAGING AND FNAC CYTOLOGY. PPV(positive predictive value) close to 100%.

6. Core needle biopsy(CNB) CNB offers advantages in Definitively diagnosing invasive carcinoma Assessing mammographically detected calcifications Assisting with proliferative lesions. But it is also a sampling device similar to FNAC.

7. Disadvantages of CNB CNB is more invasive, time consuming. Has a higher rate of complications Has a greater cost for both the biopsy equipment and the required histopathological laboratory processing and reporting Rare cases of needle track seeding of carcinoma have also been reported.

8. Aims of the system To standardize and improve the reporting of breast cytology Establish best practice guidelines Improve training in the performance and interpretation of breast cytology Clarify communication between cytopathologists and breast clinician To link this reporting system with patient management so as to facilitate optimal breast care

9. Present Systems for reporting breast FNAC

10. Reporting format details A statement of whether the lesion is completely benign , such as “No malignant cells are seen”. A statement of cellularity which is a measure of the adequacy of the material. A cytological description including any diagnostic criteria or check list of features and a brief discussion of the features which support various possible diagnoses. A conclusion or summary with a standardized descriptive diagnosis of the lesion which should point to a specific a diagnosis. A code or category can be placed in the body of the report but not in the conclusion.

11. The IAC Yokohama Reporting System emphasizes the importance of skilled biopsy and smear making techniques to optimize quality and enhance FNAC diagnosis.

12. The key elements to the breast FNAC procedure are the careful selection of a line of approach for the needle Fixation of the lesion by palpation or palpation around an ultrasound probe A rapidly performed puncture of the lesion using a rapid out from the immobilized lesion, with appropriate use of aspiration. Ultrasound for guidance and visualization of the needle tip throughout the procedure Good training and continued monitoring are essential

13. The System suggests that ideally both air-dried Giemsa -stained direct smears and alcohol-fixed Papanicolaou stained slides should be prepared utilizing a method of splitting the material obtained on each needle pass. Routine rinsing of the needle or separate passes for cell block preparation to enable immunohistochemistry for prognostic indicators can be utilized . Liquid-based cytology preparations can also be considered.

14. The IAC Yokohama System has five categories that can be stratified by their risk of malignancy (ROM): Insufficient/inadequate Benign Atypical Suspicious of malignancy Malignant

15. Category - Insufficient/inadequate Definition : The smears are too sparsely cellular or too poorly smeared or fixed to allow a cytomorphological diagnosis. FNAC smears are regarded as adequate or inadequate based on the assessment of the material on the slides. Risk of malignancy-2.6–4.8 %

16. Adequacy criteria At least seven clusters each consisting of 20 or more epithelial cells along with presence of myoepithelial cells. If material is sufficient- categorize FNAC on the basis of that material. However this is not the only criteria if the cytological findings correlate with the clinical and imaging findings in the triple test and are sufficient to make a precise diagnosis.

17. Exceptions to the adequacy criteria Pus consistent with an abscess A proteinaceous background with or without histiocytes consistent with cyst contents when the cyst has been drained under imaging or has no residual mass to palpation fat tissue fragments consistent with a lipoma or fatty nodule, spindle cell lesions and fat necrosis Reactive lymphoid material consistent with an intramammary lymph node, or in case of a hyalinized fibroadenoma which correlates with imaging.

18. If no clinical or imaging information is provided such as “completely drained cyst” and the review of the case is not possible, dispatch the report with the advice “ correlation with clinical and imaging findings is required because the FNAC findings may not represent the lesion .”

19. If the triple assessment is discrepant and the FNAC material does not explain the imaging or clinical findings , then the FNAC report should contain a statement that “ the material may not represent the lesion ,” and further FNAC or usually CNB is required.

20. Management Insufficient smears due to technical issues , repeat FNAC to a maximum of three times . Insufficient smears due to a lack of sufficient cellularity to explain the clinical or imaging expected diagnosis, repeat FNAC. Lesion is benign on imaging - follow up after 3-6 months. Indeterminate or suspicious imaging - repeat FNAC/CNB is mandatory. If no imaging available- correlate the clinical and FNAC findings and repeat FNAC .

21. Category: Benign Definition : A benign breast FNAC diagnosis is made in cases that have definite benign cytological features, which may or may not be diagnostic of a specific benign lesion. Risk of malignancy- 1–3%

22. Cytological features of benign lesions Predominantly large cohesive 3-D tissue fragments and flat mono-layered sheets consisting of evenly spaced, ductal epithelial cells with myoepithelial cells creating a “ bimodal ” pattern, as well as, “ bare bipolar nuclei ” representing stripped myoepithelial nuclei, in the background.

23. Common benign lesions Acute Mastitis Breast Abscess Granulomatous Mastitis due to TB and other nonspecific inflammatory processes Foreign Body Reactions such as with silicone fat necrosis Cysts with apocrine sheets in a proteinaceous background Fibrocystic Change with apocrine sheets and small cohesive ductal epithelial tissue fragments in a proteinaceous background

24. Material “ Consistent With Cyst Contents ” when there is a granular proteinaceous background with no epithelium and there is correlation with imaging and clinical findings and the cyst completely drained Usual Epithelial Hyperplasia with cohesive large ductal epithelial tissue fragments with myoepithelial cells and with bare bipolar nuclei in a clean background

25. Fibroadenoma with large ductal epithelial tissue fragments and plentiful bare bipolar nuclei and fibrillary or rounded stromal fragments. Intraductal Papilloma with large ductal epithelial tissue fragments, along with papillary stellate and more complex meshwork fragments, apocrine sheets and siderophages in a proteinaceous background

26. Gynaecomastia resembles epithelial hyperplasia with or without scanty stroma Intramammary lymph nodes show a heterogeneous lymphoid population with predominantly small lymphocytes. Lactational change with small acinar sheets of vacuolated cells and stripped acinar nuclei in a milky proteinaceous background including fine fat globules

27. Normal breast tissue showing larger ductal nuclei with bland chromatin and smaller oval darker myoepithelial nuclei; bare bipolar oval nuclei in the background ( Giemsa , ×400).

28. BENIGN –SUBAREOLAR ABSCESS A high yield of inflammatory cells and multinucleated giant cells. Keratin and squamous metaplastic cells. The identification of giant cells with keratin in cytoplasm is an important clue for the diagnosis. Reactive epithelial cells.

29. Staghorn clusters of epithelial cells which are cuboidal to columnar with round nuclei and fine granular chromatin bordered by bipolar nuclei- papilloma (400x)

30. Cyst: sheet of metaplastic apocrine cells and histiocytes and multinucleated histiocytes in a proteinaceous background (Giemsa,x200).

31. Fibrocystic change Sheets of apocrine cells slightly enlarged cohesive tissue fragments of ductal epithelial cells with small, oval and dark myoepithelial nuclei, oval bare bipolar nuclei and some histiocytes and multinucleated histiocytes in a thin proteinaceous background ( Giemsa , ×100).

32. Fibroadenoma:Ductal epithelial tissue fragments, an irregular fragment of myxoid stroma and bare bipolar nuclei with some dispersed cells in the background; a small aggregate of histiocytes is also present ( Giemsa , ×100)

33. MANAGEMENT Review clinical and imaging findings: if “triple test” benign, no further biopsy required, and review depends on the nature of the lesion. If clinical and/or imaging indeterminate or suspicious, repeat FNAC or proceed to CNB

34. Category: Atypical Definition : The term atypical in breast FNAC is defined as the presence of cytological features seen predominantly in benign processes or lesions, but with the addition of some features that are uncommon in benign lesions and which may be seen in malignant lesions. Risk of malignancy- 22-39%

35. Cytological features High cellularity Increased dispersal of single intact cells Enlargement and pleomorphism of nuclei Presence of necrosis or mucin Complex micropapillary or cribriform architecture of epithelial tissue fragments

36. Lesions associated Usual epithelial hyperplasia- by itself or associated with fibrocystic change Fibroadenomas with Atypia Radial scars Intraductal papillomas Adenomyoepithelioma Spindle cell lesions

37. Epithelial sheet showing nuclear variation in size, chromatin and shape, multinucleation and infiltrating histiocytes , could be regarded as atypical; but a low N:C ratio, apocrine cytoplasmic differentiation, histiocytes and a proteinaceous background are present ( Giemsa , ×400).

38. Dispersed cells with mildly variable nuclei could be regarded as atypical, but they are apocrine cells with a low N:C ratio with evidence of crush artefact in the chromatinic smearing ( Giemsa , ×100)

39. Atypical stromal fragment showing mild hypercellularity and mild nuclear enlargement and atypia with two ductal epithelial tissue fragments and occasional spindle stromal cells in the background, raising the possibility of a low-grade phyllodes tumor (Pap, ×200).

40. Large clusters of spindle cells embedded in fibromyxoid stroma . Individual cells are oval to spindle shaped with plump fusiform nuclei

41. Otherwise typical fibroadenoma with a (central) cohesive tissue fragment of ductal epithelial cells with myoepithelial cells, and two tissue fragments (right and bottom left) showing atypical crowding, nuclear overlapping and mild nuclear enlargement. Bare bipolar nuclei in the background ( Giemsa , ×200)

42. Epithelial hyperplasia: large cohesive irregular ductal epithelial tissue fragment with slit-like secondary lumina and dark oval myoepithelial nuclei in a clean background with oval bare bipolar nuclei ( Giemsa , ×100).

43. MANAGEMENT Atypical diagnosis due to a technical problem - Repeat FNAC. If either or both the clinical and imaging findings are indeterminate or suspicious a repeat FNAC/CNB is mandatory. If neither clinical nor imaging findings are of concern-depending on the lesion, the management options include to repeat the FNAC/CNB, or to review the patient with imaging at 3–6 months, with subsequent repeat FNAC/CNB if the lesion has changed.

44. Category: Suspicious of Malignancy Definition : The term “suspicious of malignancy” in breast FNAC is defined as the presence of some cytomorphological features, which are usually found in malignant lesions, but with insufficient malignant features, either in number or quality, to make a definitive diagnosis of malignancy. The type of malignancy suspected should be stated whenever possible. Risk of malignancy- 84.6–97.1%

45. Low grade ductal carcinoma in situ(LGDCIS) Highly cellular smears including a range of solid, cribriform , micropapillary , papillary and solid papillary subtypes May be associated with microcalcifications . Marked increase in dispersed single cells showing mild to moderate nuclear atypia , a greatly reduced number or total lack of myoepithelial cells associated with the epithelial tissue fragments, and scant or absent bare bipolar nuclei in the background. FNAC cannot specifically diagnose LGDCIS and at the same time exclude invasive carcinoma

46. High-grade ductal carcinoma in situ (HGDCIS) The diagnosis by FNAC is controversial as it cannot exclude invasive carcinoma. HGDCIS is often associated with casting pleomorphic calcifications on mammography, and occasionally may produce a palpable or imaging mass lesion in the absence of invasive carcinoma. May be associated with extensive necrosis, calcifications and high-grade nuclear atypia in dispersed single epithelial cells and both small and larger crowded epithelial tissue fragments..

47. The smears are often low in cellularity reflecting the small volume of cancer cells in ducts relative to breast tissue. These findings cannot exclude high grade invasive carcinomas, particularly those of no special type and metaplastic carcinomas, which can also show necrosis

48. Papillary tissue fragment consisting of thin fibrovascular branching stroma , covered in crowded epithelium, suggesting a papillary intraductal carcinoma in situ; the suggested categorization is “suspicious of malignancy” (Pap, ×100)

49. Large epithelial tissue fragment showing a cribriform architecture, with crowded cells, mild nuclear pleomorphism and a tendency for the nuclei to orientate to the luminal spaces rather than stream, suggesting cribriform intraductal carcinoma; the suggested categorization is “suspicious of malignancy” ( Giemsa , ×100).

50. Dispersed single intact cells with large hyperchromatic pleomorphic nuclei and occasional prominent nucleoli, juxtaposed to a ductal epithelial tissue fragment (upper) with regular ductal nuclei and plentiful oval dark myoepithelial nuclei: the decision to call this lesion “carcinoma” or to categorize it “suspicious of malignancy,” because of the presence of a benign component, will depend on the amount of malignant material ( Giemsa , ×400)

51. MANAGEMENT A “suspicious of malignancy” FNAB cytology diagnosis should lead to review of the imaging findings, but further biopsy(CNB) is an absolute requirement. If CNB is not available, then surgical excision biopsy is required before specific treatment in almost all cases.

52. Category: Malignant Definition : A malignant cytological diagnosis is an unequivocal statement that the material is malignant, and the type of malignancy identified should be stated whenever possible. The malignant diagnosis should only be used when there is a full constellation of cytological findings and no discrepant features. Risk of malignancy- 99.0–100%

53. Cytological features High cellularity Prominent dispersal of single cells Crowded tissue fragments with overlapping nuclei Nuclear enlargement Anisonucleosis Pleomorphism of the nuclear margin, size and chromatin Hyperchromasia

54. Prominent nucleoli Tubular architecture of epithelial fragments Intracytoplasmic lumina in atypical epithelial cells and elastoid fragments The presence of stromal fragments infiltrated by carcinoma in breast smears resembling smaller fragment seen in CNB is as being categorical evidence of invasive carcinoma.

55. Carcinomas diagnosed most commonly by FNAC include No special type( ductal ) Lobular Mucinous Tubular Metaplastic carcinoma with medullary features Adenoid cystic carcinoma Carcinoma with apocrine differentiation Carcinoma with neuroendocrine features Carcinoma with osteoclastic giant cells

56. MANAGEMENT A malignant FNAC diagnosis should be correlated with the clinical and imaging findings, and if the triple test is concordant and material is available in the cell block for prognostic and treatment markers, definitive therapy including neoadjuvant chemotherapy and surgery can be commenced.

57. If the axillary lymph nodes are palpable or enlarged or suspicious on ultrasound of the axilla , FNAC is recommended to stage the patient who has presented with a breast lesion.

58. Dispersed single cells and discohesive small tissue fragments of intermediate-sized cells with a high N:C ratio and moderately enlarged and mildly pleomorphic nuclei with small nucleoli, in a fibrillary mucinous background. Mucinous carcinoma on histopathology (Pap, ×400).

59. Carcinoma in fraying, discohesive tissue fragments with high-grade, enlarged pleomorphic nuclei showing irregular granular chromatin and nucleoli, a variable but often high N:C ratio and a suggestion of gland formation (upper right). Carcinoma of no specific type on histopathology (Pap, ×200).

60. Carcinoma with intermediate-sized cells, mildly enlarged, mildly pleomorphic nuclei (note the comparison in size to the macrophage nucleus, top center) and eccentric cytoplasm containing an occasional vacuole in some cells. Lobular carcinoma on histopathology ( Giemsa , ×400).

61. Ancillary Techniques Immunocytochemistry - diagnostic difficulties utilizing myoepithelial cell markers on cell block material in atypical and suspicious lesions Immunohistochemistry - on cell blocks for the prognostic and predictive markers for estrogen, progesterone and HER2 receptors. for the determination of a primary site in metastatic lesions; and the study of prognostic and predictive markers in the metastatic breast cancer setting Molecular techniques - in situ hybridization for HER2 on cell blocks

62. Thank You