|Year : 2019 | Volume
| Issue : 4 | Page : 250-256
The role of FNAC in diagnostically challenging malignant lesions of breast
Rajyalakshmi Rallapalli1, Lakshmi V Chavali1, Bhaskar V Rani1, Ramana V Kada2, Beulah P Maddirala1
1 Department of Pathology, Rangaraya Medical College, Kakinada, Andhra Pradesh, India
2 Department of Radiology, Satya Scan and Diagnostics, Kakinada, Andhra Pradesh, India
|Date of Submission||09-Aug-2019|
|Date of Decision||17-Oct-2019|
|Date of Acceptance||29-Oct-2019|
|Date of Web Publication||16-Dec-2019|
Dr. Rajyalakshmi Rallapalli
Department of Pathology, Rangaraya Medical College, Kakinada, Andhra Pradesh - 533 001
Source of Support: None, Conflict of Interest: None
Background: Fine needle aspiration cytology is a simple investigation to evaluate the malignant tumors of the breast when compared to tru-cut biopsy. It is invaluable in the diagnosis of the common invasive carcinoma of the breast including its subtypes. The morphology of the uncommon subtypes and other rare tumors are the source of diagnostic confusion.
Aims: The objective of this study is to assess the role of FNAC in diagnostically challenging malignant lesions of the breast.
Methods and Material: The study included 526 female patients with palpable breast lumps subjected to FNAC for one year from November 2015 to October 2016 in the department of pathology. The cytology features of these patients were studied and correlated with histopathology.
Results: Diagnostic difficulty was encountered in certain tumors having either bland cytology or a predominant discrete pattern or a combination of extracellular mucin and papillary pattern. These were reanalyzed in correlation with histopathology, clinical findings, radiology and immunohistochemistry.
Conclusions: Awareness of the morphology of these rare lesions improves the diagnostic accuracy making cytology a more efficient tool for the preoperative assessment of malignant breast tumors.
Keywords: Breast, cribriform, Fine needle aspiration cytology, micropapillae, plasmacytoma
|How to cite this article:|
Rallapalli R, Chavali LV, Rani BV, Kada RV, Maddirala BP. The role of FNAC in diagnostically challenging malignant lesions of breast. J NTR Univ Health Sci 2019;8:250-6
|How to cite this URL:|
Rallapalli R, Chavali LV, Rani BV, Kada RV, Maddirala BP. The role of FNAC in diagnostically challenging malignant lesions of breast. J NTR Univ Health Sci [serial online] 2019 [cited 2020 Aug 15];8:250-6. Available from: http://www.jdrntruhs.org/text.asp?2019/8/4/250/273136
| Introduction|| |
Fine needle aspiration cytology (FNAC) is a simple yet valuable preoperative investigation for the diagnosis of breast lesions including malignancy. Knowledge about the cytology of the different malignant lesions of the breast is essential for their diagnostic and prognostic relevance. Carcinoma of breast is classified based on morphology and molecular profile into several types. Invasive carcinoma of no special type, the most common malignancy of the breast, with its characteristic cytology provides an accurate interpretation in the majority. However, in some malignant lesions, unusual morphology and unfamiliarity pose a diagnostic challenge. Carcinomas with bland nuclear features and cohesive morphology may be erroneously interpreted as benign neoplasms. Similarly, accurate diagnosis of rare tumor types is not always possible. Careful observation of cytology patterns and subtle cellular details help to minimize the errors. FNAC, one of the most simple and cost-effective investigations, is still a valuable tool in the hands of an experienced pathologist in Indian scenario.
Herein, we describe the cytology features of seven such malignant tumors of the breast which posed diagnostic difficulties on FNAC. The present study is an attempt to correlate these unusual cytology features with corresponding histopathology and to assess the utility of FNAC in providing an accurate preoperative cytology diagnosis of malignant breast lesions.
| Methods|| |
A total of 526 female patients with palpable breast lumps were subjected to FNAC over a period of one year, from November 2015 to October 2016 at the Department of Pathology. The smears were stained with Hematoxylin and Eosin and May-Grunwald-Giemsa stains. The cytomorphology of all lesions interpreted as malignant and suspicious of malignancy were correlated with clinical and histopathology findings. The cases with discrepancy of cytological and histopathological diagnosis were reanalyzed with clinical and radiology findings. Immunohistochemistry was done for the available cases.
| Results|| |
The patient age group ranged from 35-70 years. Cytology features of all 526 breast lumps were analyzed, of which, a definitive diagnosis was possible in 519 cases. There were 21 inflammatory lesions, 413 benign and 85 malignant tumors. Unusual cytology with cyto-histopathology discrepancies was noted in seven out of 85 malignant lesions. The clinical and radiology details of the seven cases are tabulated in [Table 1]. The cytology features are tabulated in [Table 2].
|Table 1: Clinical and Radiology Features Along with Cyto-Histopathology Diagnosis|
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| Discussion|| |
The use of core needle biopsy for evaluating carcinoma breast is increasing as it provides not only an accurate diagnosis but also material for immunohistochemistry. However, the disadvantages are that it is expensive, time consuming, painful and demands technical expertise. On the other hand, FNAC is a simple, rapid and cost-effective investigation of choice for the preoperative assessment of malignant lesions of the breast, especially in developing countries like India., When correlated with clinical and radiology findings, cytology gives accurate results. However, difficulties in interpreting ductal carcinoma in situ (DCIS) and carcinomas with bland nuclear features are some limitations to FNAC. These can be overcome, when FNAC is done and interpreted by a skilled pathologist, with the results comparable to that of core biopsy., The role of cytology thus can be extended from mere diagnosing carcinoma to subtyping and even identifying subtle lesions like DCIS.
Most of the lesions in the present study were uncommon, making the cytology features unfamiliar. Lack of dis-cohesiveness, pleomorphism, high nuclear-cytoplasmic ratio or nucleoli led to confusion with benign tumors in a few. Unusual patterns contributed to diagnostic difficulties in some.
We addressed the diagnostic discrepancies by categorizing the seven cases into three groups based on the morphology. They are:
- Tumors with bland morphology (3)
- Tumors with predominant discrete pattern (3)
- Tumors with a combination of papillae and mucin (1).
Tumors with bland morphology
DCIS and papillary neoplasms (PN) are the two challenging lesions to interpret on cytology of breast masses due to their relatively benign appearance. We encountered two such tumors.
Case 1: Cytology (Cyt): DCIS/Histopathology (HP): DCIS with microinvasion [Figure 1]a, [Figure 1]b.
|Figure 1: Case 1: (a) Cytology smear exhibiting cribriform pattern. (H and E, x200). (b) HP showing cribriform DCIS. (H and E, ×200). Case 2: (c) Abortive branching papilla on cytology. (H and E, ×400). (d) Micropapillary DCIS on HP (H and E ×200). Case 3: (e1) Cytology smear showing discrete bland cells. (H and E, ×200). (e2) Nuclear grooves (×1000). (f) Angulated tubules on HP (H and E, ×400)|
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With mammography, the detection rate of DCIS has increased., The diagnosis of DCIS on cytology, though difficult, is significant as it influences the management. With accurate interpretation, radical surgery can be avoided. Large sheets of overlapping and cohesive epithelial cells exhibiting mild to moderate atypia, without bare oval nuclei or discrete cells and presence of foci of necrosis led to the conclusion of DCIS in the present case. Malignant cells invading fat and stromal fragments, the signs of invasion were not observed. Histopathology revealed micro invasive DCIS with predominant cribriform type. Review of the smears showed punched out holes within the sheets, which is the hallmark of cribriform DCIS. Though we could diagnose this case as DCIS on FNAC, subtyping was not offered for this rare case of palpable DCIS.
Case 2: Cyt: PN favoring malignancy/HP: Micropapillary DCIS with cystic change [Figure 1]c,[Figure 1] d.
FNAC yielded 5 ml of blood stained fluid on initial aspiration. Smears from the residual swelling were cellular and showed plenty of abortive branching micropapillae, few single cells and hemosiderin-laden macrophages. Bare oval nuclei were not seen. Histopathology showed many dilated ducts and cysts lined by branching micropapillae reflecting the cytology picture. Papillary neoplasms are difficult to diagnose and classify both on cytology and core needle biopsy. Micropapillary DCIS in its pure form is extremely uncommon. It is a low grade DCIS with a propensity for cystic change, multicentricity, microinvasion and recurrences. Whilst papillary DCIS is known for its heterogeneous morphology like monolayered sheets, micropapillae, solid and cribriform aggregates, little is known about the cytology of micropapillary DCIS. Presence of true papilla with fibrovascular cores and columnar nature of dispersed cells are characteristic of usual type papillary neoplasms. Highly cellular smears with complex papillary fragments, discrete cells and absence of macrophages and bare nuclei are features favoring malignancy. The present case suggests that we need to consider the possibility of micropapillary DCIS when many micropapillae are present in an aspirate from a cystic lesion. This case also highlights the importance of aspiration from residual swelling in cystic lesions.
Case 3: Cyt: Suspicious of malignancy/HP: Tubulolobular carcinoma (TLC) [Figure 1]e, [Figure 1]f.
TLC is a rare malignant tumor of the breast with histology features of both tubular and lobular carcinoma. TLC with bland nuclear morphology is another difficult case to diagnose on cytology. The cytology described by various authors is the occurrence of monomorphic population of small cells with intracytoplasmic vacuoles, nuclear grooves and cerebriform nuclei, single files and tubules., In view of the presence of monolayered sheets of cohesive epithelial cells with bland nuclei along with few discrete cells and absence of bare oval nuclei in the background, we labeled our case as suspicious for malignancy. Histopathology showed the picture of tubulo-lobular carcinoma. Review of the cytology smears showed that the tumor cells were having nuclear grooves and cerebriform nuclei, useful diagnostic clues, which were missed on the initial interpretation.
The relative bland cytology of the above three cases simulates the morphology of benign neoplasms. The lack of bare oval nuclei and the presence of few discrete cells are important indicators for malignancy, along with the subtle signs like cerebriform nuclei and nuclear grooves.
Tumors with predominant discrete pattern
Loss of cell cohesion, an important aspect of malignancy, can sometimes be the predominant component on FNAC and suggest a specific diagnosis in certain subtypes like lobular, solid papillary and medullary carcinoma. The three malignant tumors with predominant discrete pattern, in the present study, were solid papillary carcinoma (SPC), medullary carcinoma (MC) and plasmacytoma.
Case 4: Cyt: Invasive lobular carcinoma (ILC)/HP: SPC [Figure 2]a and b].
|Figure 2: Case 4: (a) Bland plasmacytoid cells on cytology. (H and E, ×400). (b) HP showing SPC. (H and E, ×200). Case 5: (c) Polygonal epithelial cells and lymphocytes on cytology. (H and E, ×400). (d) MC on HP (H and E ×200). Case 6: (e) Discrete plasma cells on cytology. (H and E, ×400). (f) Plasmacytoma on HP (H and E, ×400)|
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Solid papillary carcinoma, a variant of breast carcinoma with a favorable prognosis can be determined on cytology by its typical features. The smears are hypercellular with a discretely distributed small bland plasmacytoid cells having low nuclear cytoplasmic ratio. Intra and extracellular mucin as observed in our case is another significant clue. Similar plasmacytoid morphology, discrete pattern and intracytoplasmic vacuoles are seen in ILC, which however can be distinguished by moderate cellularity, linear arrangement, high nuclear cytoplasmic ratio and hyperchomatic nuclei., Dis-cohesiveness and plasmacytoid appearance of SPC are attributed to the neuroendocrine differentiation of these tumors.
Case 5: Cyt: Histiocytic variant of ILC/HP: MC [Figure 2]c, [Figure 1]d.
Medullary carcinoma of breast, which needs stringent criteria to categorize on histology, has unique cytology. It shows syncytial aggregates as well as discretely arranged large pleomorphic cells with nucleoli in a lympho-plasmacytic background., Unlike the above description, our case showed a predominant discrete pattern of large polygonal squamoid or histiocyte-like cells with low nuclear cytoplasmic ratio and occasional loose aggregate formation. Unfamiliarity with these findings and ignoring background lymphocytes led us to the wrong diagnosis of histiocytic variant of ILC, a rare carcinoma composed of polygonal cells with abundant eosinophilic cytoplasm.
Histopathology and immunohistochemistry revealed typical triple negative medullary carcinoma. The background lymphocytes, though sparse need to be taken into account while interpreting the smear. Also, clinically the tumor was well-defined and mobile mimicking a fibroadenoma, highlighting the importance of clinical correlation with cytology features.
Case 6: Cyt: Invasive carcinoma of no special type (ICN) or ILC/HP: Plasmacytoma [Figure 2]e, [Figure 1]f.
Primary plasmacytoma of breast is an extremely uncommon neoplasm. The cytology can be mistaken for different types of primary breast carcinomas like lobular carcinoma, solid papillary carcinoma or ICN by even an experienced cytopathologist. Perinuclear hof, cart-wheel chromatin and bluish cytoplasm are the typical features of plasma cells which are better appreciated on MGG stain., These findings were observed only focally in our case. The presence of discretely arranged plasmacytoid cells along with binucleate and multinucleate cells on cytology and a diffuse lump involving the entire breast clinically are the two important clues in diagnosing the present case, which we appreciated retrospectively. Pleomorphic ILC, a mimic of plasmacytoma, shows overlapping features like dis-cohesiveness, relatively small sized cells and plasmacytoid appearance. But the presence of cells with intracytoplasmic lumina containing mucin, clinches the diagnosis., Similarly, few cases of ICN with predominant discrete pattern resemble ILC and hence mimic a plasmacytoma. Histopathology followed by immunohistochemistry confirmed the diagnosis of Plasmacytoma. (CD 138 was positive and CK negative) This case highlights the importance of high index of suspicion in cases with unusual clinical and cytology presentation.
In the above three lesions, cytology features were undoubtedly malignant. However, a more precise diagnosis can be rendered by the recognition of distinctive features unique to these tumors.
Tumors with a combination of papillae and mucin
Case 7: Cyt: Mucinous carcinoma or Papillary carcinoma/HP: Micropapillary variant of mucinous carcinoma (MPMC) [Figure 3].
|Figure 3: Case 7: (a) Branching micropapillae on cytology (Please note spelling of micropapillae is wrong) (b) Papillae surrounded by cytoplasm on cytology. (c) MPMC on HP (d) Algorithm for the diagnosis of MPMC and MC|
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MPMC, an aggressive variant of mucinous carcinoma can be distinguished from conventional mucinous carcinoma by its distinct cytology. Presence of high cellularity with many papillae and micropapillae, as in a papillary neoplasm and mucinous background with capillaries similar to mucinous carcinoma prompted us to give differential diagnoses of papillary and mucinous carcinoma. The cytology features in favor of MPMC are micropapillae, cells balls and cohesive clusters of cells with low nuclear grade in an abundant mucinous background., Few papillae in the present case were surrounded by an apical portion of cytoplasm, a feature not described on cytology before. The differential diagnoses to be considered are mucinous carcinoma, invasive micropapillary carcinoma and micropapillary DCIS. Less cellular smears with abundant mucin, cohesive sheets and absence of micropapillae favor conventional mucinous carcinoma. Invasive micropapillary carcinoma, a high-grade carcinoma with a propensity for angioinvasion also shows micropapillae similar to MPMC., The clinching features are angulated clusters and branching papillae of pleomorphic cells and absence of mucin.,,
[Figure 4] shows the algorithms for tumors with bland morphology and those with discrete pattern.
|Figure 4: Picture depicting algorithms for tumors with bland morphology and those with predominant discrete pattern|
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| Conclusion|| |
In this era of core biopsies, cytology still holds good in the preoperative evaluation of palpable tumors of the breast. It is an accurate and cost-effective alternative to core biopsies when the cytopathologist has the acumen and knowledge about the morphology of these rare types. The triad of clinical assessment, radiology findings and cytology features, in combination with cell-block is the best alternative to core biopsy, which is still in novice state in many places in India. Our study shows that FNAC is a useful diagnostic tool not only for identifying ICN, but also for recognizing diagnostically challenging carcinoma variants and rare hematopoietic lesions like plasmacytoma. Awareness and knowledge of the cytology features of these tumors contribute to a definitive diagnosis, thereby improving the specificity.
To the patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Saha A, Mukhopadhyay M, Das C, Sarkar K, Saha AK, Sarkar DK. FNAC versus core needle biopsy: A comparative study in evaluation of palpable breast lump. J Clin Dign Res 2016;10:EC05-8.
Mitra S, Dey P. Fine-needle aspiration and core biopsy in the diagnosis of breast lesions: A comparison and review of the literature. Cytojournal 2016;13:18.
] [Full text]
McKee GT, Tildsley G, Hammond S. Cytologic diagnosis and grading of ductal carcinoma in situ
. Cancer Cytopathol 1999;87:203-9.
Sauer T, Lemo J, Garred O, Naess O. Cytologic features of ductal carcinoma in situ
of the breast mirror the histopathologic growth pattern heterogeneity and grading. Cancer Cytopathol 2005;105:21-7.
Castellano I, Marchio C, Tomatis M, Ponti A, Casella D, Bianchi S, et al.
Micropapillary ductal carcinoma in situ
of the breast: An inter-institutional study. Mod Pathol 2010;23:260-9.
Mitra S, Dey P. Grey zone lesions of breast: Potential areas of error in cytology. J Cytol 2015;32:145-52.
] [Full text]
Das DK, Haji BI, Abdeen SM, John B, Sheikh M, Al-Bader I, et al.
Tubulolobular carcinoma of the breast with grooved and cerebriform nuclei: Failure to identify this specific subtype in a case during routine fine needle aspiration cytology and histopathological diagnosis. Diagn Pathol 2011;39:54-9.
Boppana S, Erroll M, Reiches E, Hoda SA. Cytologic characteristics of tubulolobular carcinoma of the breast. Acta Cytol 1996;40:465-71.
Wakasa T, Nakamura M, Kagiya T, Taniguchi E, Sakurai T, Kakudo K. Loss of cellular cohesion in cytology composes a special subgroup of breast tumors-analysis of 37 cases. Acta Cytol 2014;58:89-95.
Yamada M, Otsuki Y, Shimizu SI, Tanioka F, Ogawa H, Kobayashi H. Cytological study of 20 cases of solid-papillary carcinoma of the breast. Diagn Cytopathol 2007;35:417-22.
Rajesh L, Dey P, Joshi K. Fine needle aspiration cytology of lobular breast carcinoma. Comparision with other breast lesions. Acta Cytol 2003;47:177-8.
Racz MM, Pommier RF, Troxel ML. Fine needle aspiration cytology of medullary breast carcinoma: Report of two cases and review of the literature with emphasis on differential diagnosis. Diagn Cytopathol 2007;35:313-8.
Netra SM, Vani BR, Murthy VS. Cytomorphological study of medullary carcinoma of breast in comparison to infiltrating ductal carcinoma. J Cytol 2018;35:195-8.
] [Full text]
De Chiara A, Losito S, Terracciano L, Di Giacomo R, Iaccarino G, Rubolotta MR. Primary plasmacytoma of the breast. Arch Pathol Lab Med 2001;125:1078-80.
Pai R, Kini H, Ghartimagar D. Secondary extramedullary plasmacytoma of the breast: Diagnosed by fine needle aspiration cytology. Kathmandu Uni Med J 2007;5:538-40.
Mutreja D, Kinra P, Patil SD, Tewari V. Plasmacytoid appearance of tumor cells in breast aspirates on fine needle aspiration cytology: Diagnostic predicament for the cytopathologist. J Cytol 2015;32:75-6.
] [Full text]
Ng WK. Fine-needle aspiration cytology findings of an uncommon micropapillary variant of pure mucinous carcinoma of the breast. Cancer Cytopathol 2002;96:280-8.
Madur B, Shet T, Chinoy R. Cytologic findings in infiltrating micropapillary carcinoma and mucinous carcinomas with micropapillary pattern. Acta Cytol 2007;51:25-32.
Shet T, Chinoy R. Presence of a micropapillary pattern in mucinous carcinomas of the breast and its impact on the clinical behavior. Breast J 2008;14:412-20.
Khurana KK, Wilbur D, Dawson AE. Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast. Acta Cytol 1997;41:1394-8.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]