Presented in part in a platform format at the Canadian Association of Pathologists/Royal College of Physicians and Surgeons of Canada Annual Meeting, Halifax, Nova Scotia, Canada, September 25-29, 1996.
The pleomorphic variant of invasive lobular carcinoma shares the typical infiltrating histologic pattern of classic invasive lobular carcinoma, but differs from it in its nuclear pleomorphism and aggressive behavior. The purpose of this study was to describe the fine-needle aspiration (FNA) cytologic findings of the pleomorphic variant of lobular carcinoma and to compare them with those of classic lobular carcinoma.
Among 405 breast FNA performed in 1995, 7 examples of classic infiltrating lobular carcinoma and 4 cases of this neoplasm's pleomorphic variant were identified; all were histologically confirmed. The FNA from three of the four pleomorphic variant cases and from two of the seven classic lobular carcinoma cases were diagnostic of malignancy; these were evaluated for a variety of cytologic criteria, which were graded from 0 to 3.
Although exhibiting many cytologic features in common with the classic type, such as indian files and cytoplasmic vacuoles, the FNA of the pleomorphic variant differed in their tendency to yield greater cellularity, larger cell size, and, particularly, more pleomorphic nuclei.
Fine-needle aspiration (FNA) is a valuable investigative tool for the workup of breast masses.1-3 Although the cytologic features of invasive lobular carcinoma of the classic type (CL) from FNA specimens have been well described,1-9 there are few data on those of the pleomorphic variant of lobular carcinoma (PV).10 The PV, a diagnostic entity recognized relatively recently, is thought to behave more aggressively than CL.11, 12 In this article, the authors review their experience with the FNA cytology of PV and compare its FNA features with those of CL.
MATERIALS AND METHODS
The surgical pathology files of the Royal Victoria Hospital for the year 1995 were searched for diagnoses of invasive lobular carcinoma. Of the 28 cases identified, 11 had corresponding breast FNA material obtained prior to the surgical excision. These 11 FNAs corresponded to 2.7% of the total 405 breast FNAs seen in the department in 1995. These 11 FNAs had all been obtained using either 22- or 23-gauge needles. The breakdown of the diagnoses on the surgical material of these 11 cases was CL in 7 cases and PV in 4 cases. The diagnosis of PV on the surgical material was restricted to invasive carcinomas that showed the infiltrating pattern of CL but in which the nuclei were more pleomorphic than those of CL, as described previously.11-13 The surgical material was comprised of segmental mastectomies in all cases, with axillary dissections in all but one case. The patients' ages ranged from 48 to 69 years (median, 63 years) for the CL group and from 51 to 67 years (median, 56 years) for the PV group. Of the patients who underwent axillary dissection, four of six patients in the CL group and two of the four patients in the PV group had lymph node metastases.
Of the seven cases that proved to be CL on surgical material, the original FNA diagnoses were “malignant cells present most consistent with lobular carcinoma” in two cases whereas the remaining five were diagnosed as “unsatisfactory due to hypocellularity.” Of the four cases that proved to be PV on surgical material, the original FNA diagnoses were “carcinoma, type unclear, i.e., ductal versus lobular” in three cases whereas the fourth was diagnosed as “suspicious of malignancy, interpretation limited by air-drying artefact.” Upon review, all the original diagnoses given on the FNAs were confirmed.
Of these FNAs, only the cases in which a definitive diagnosis of carcinoma (i.e., two cases of CL and three cases of PV) was made were kept for the assessment of the cytologic criteria. These five FNAs were evaluated without knowledge of the subsequent surgical diagnosis for the following features: cellularity, single cells, indian files, cell groups, nuclear pleomorphism, cell size, nucleoli, cytoplasmic vacuoles, and signet ring cells. Each cytologic feature was graded according to the following numeric scheme: 0 (absent), 1 (mild), 2 (moderate), and 3 (prominent).
The results of the grading of the cytologic features on FNAs are compiled in Table 1. The FNAs of PV had many features in common with those of CL; the indian file arrangement (Fig. 1A) and the cytoplasmic vacuoles (Figs. 1A and B) characteristically associated with CL were also encountered in PV. However, differences were also noted. The PV had a tendency to yield more cellular specimens (Fig. 1C). In addition, the tumor cells in the PV group were larger and, especially, exhibited more pleomorphic nuclei (Fig. 1C) than in the CL group.
Table 1. Grading of Various Cytologic Features of Five Cases of Classic Type Lobular Carcinoma and the Pleomorphic Variant
Several variants of invasive lobular carcinoma have been recognized, including the solid, alveolar, and signet ring types and mixed variants. The PV of invasive lobular carcinoma was recognized less than 10 years ago.11-13 Based on histologic material, PV is defined as an invasive carcinoma with the infiltrating pattern of CL, but with more pleomorphic nuclei than CL, varying degrees of greater contour irregularity, increased mitotic activity, and/or greater nuclear size.12 The recognition of this variant of lobular carcinoma is very significant because it may behave in a more aggressive manner and may have a worse prognosis than the classic type.11, 12
For an experienced pathologist with regular exposure to breast FNAs, it is usually not difficult to distinguish CL from ductal carcinoma. The FNA cytologic features of CL have been well described in the literature.1-9 The cytologic characteristics typically associated with CL include indian files, cells of small size, cytoplasmic vacuoles, a signet ring appearance, and a lack of significant nuclear and cellular pleomorphism. In contrast, FNAs from ductal carcinoma usually display larger cells with more prominent pleomorphism.1, 3
The current study underscores the potential of PV as a cause of difficulties in typing of carcinoma in FNA material. Indeed, a diagnosis of “carcinoma, type unclear, i.e., ductal versus lobular” was offered in all three FNAs of PV that were encountered. The dilemma of typing arose from the fact that although these three FNAs were recognized as exhibiting some features of lobular carcinoma, the prominent nuclear pleomorphism and the large size of the cells were more characteristic of the ductal type. This difficulty in typing carcinomas in FNAs from PV has also been discussed in the only other report of PV in the literature.10 In fact, in the authors' experience, the presence of characteristics that are hybrid between lobular and ductal carcinoma in FNA material from the breast is an indication of the possibility that one is dealing with PV.
Lobular carcinoma of the classic type is known to be an important cause of false-negative diagnoses, often related to hypocellularity of the FNA specimens.1, 2 In the authors' experience, the FNAs of PV tend to be more cellular and are much less likely to be categorized as “unsatisfactory due to hypocellularity” than CL. This observation contrasts with the report of Dabbs et al.,10 who reported that all their FNAs from PV were sparsely cellular, as is usually observed in CL.
Although it would be difficult to make a definitive diagnosis of PV prospectively in FNA material, this diagnosis should be at least suggested in a differential diagnosis when the cytologic features mentioned earlier are encountered. It is important to accurately subtype this type of carcinoma because it carries certain clinical implications. Indeed, it is important to distinguish PV from ductal carcinoma because, compared with invasive ductal carcinoma, the incidence of cancer bilateralism is higher in all types of invasive lobular carcinoma,14 and is probably highest for PV.13 In addition, it is important to distinguish PV from CL because it is thought to behave more aggressively than CL, with an especially higher risk of recurrence.11, 12
In conclusion, the FNA features of PV are characteristically hybrid between those of ductal carcinoma and CL. It is precisely this constellation of hybrid features in breast FNA material that should suggest a diagnosis of PV.