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First published online October 16, 2007
British Journal of Radiology (2007) 80, 970-974
© 2007 British Institute of Radiology
doi: 10.1259/bjr/95130566
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Review article

Granular cell tumour of the breast: MRI findings and review of the literature

A M Scaranelo 1 K Bukhanov 1 P Crystal 1 A M Mulligan 2 and F P O'Malley 2

Departments of 1 Medical Imaging and 2 Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, ON M5G 1X5, Canada

Correspondence: Anabel M Scaranelo, Marvelle Koffler Breast Centre, 12th floor, Mount Sinai Hospital, 600 University Avenue, Toronto, ON M5G1X5, Canada. E-mail: anabel.scaranelo{at}uhn.on.ca


   Abstract
Top
 Abstract
Introduction
 Case description
 Discussion
 References
 
Granular cell tumours (GCTs) are uncommon, usually benign neoplasms that can mimic malignancy on breast imaging. GCTs can originate anywhere in the body but are most frequently found in the head and neck area, particularly in the oral cavity. When occurring in the breast, as occurs in 5–8% of all cases of GCT, the clinical presentation is similar to that of a primary breast carcinoma. We report a case of granular cell tumour of the breast presenting as a suspicious lesion on breast imaging, and review the MRI features of GCTs.


   Introduction
Top
 Abstract
 Introduction
Case description
 Discussion
 References
 
Granular cell tumour (GCT) of the breast is a relatively uncommon lesion that must be differentiated from primary breast carcinoma. Clinically, GCTs can mimic carcinoma because of their fibrous consistency and hence their hardness, thus presenting as a palpable mass. On mammography, these tumours can present as ill-defined or spiculated lesions, similar to primary carcinoma. Abrikossoff [1] first described this tumour in 1926 as "granular cell myoblastoma", assuming it was of myogenic origin; some even refer to the lesion as "Abrikossoffoma". Subsequently, immunohistochemical and ultrastructural features have proposed a perineural or Schwann cell origin. The neoplastic cells of the tumour typically express S100 and CD68 (KP-1), the latter as a result of cytoplasmic lysosome content. However, the exact histogenesis of this tumor is still unknown [2]. Distinction between benign and malignant GCTs is difficult to make because of their histological similarity and lack of reliable criteria that can predict tumour behaviour. Breast MRI, therefore, assumes an important role in delineating the extent of the disease, looking for the presence or absence of aggressive features and/or coexistence of other breast tumours, and screening the contralateral breast.


   Case description
Top
 Abstract
 Introduction
 Case description
Discussion
 References
 
A 59-year-old woman, who had an outside screening mammogram revealing a mass in her left breast, was referred to our institution for further evaluation. Physical examination revealed a palpable painless lesion in her left breast at the 1 o'clock position 12 cm from the nipple. Standard mammography, including a mediolateral oblique (MLO) and craniocaudal (CC) view, showed a 2.0 cm round dense mass (Figure 1Go) with spiculated margins in the upper outer quadrant of the left breast, best seen in MLO view close to the tail of Spencer, 13 cm from the nipple. There were no previous mammograms available for comparison. Real-time sonography using a model HDI 5000 scanner (Philips/Advanced Technology Laboratories Ultrasound, Bothell, Wash), with a frequency range of 5–12 MHz, and colour-Doppler demonstrated a round, hypoechoic (with some areas almost anechoic), complex pattern, solid mass with angular margins and a strong echogenic halo (Figure 2aGo) measuring 1.8x1.9x1.8 cm at the 1 o'clock position of the left breast, near the axilla and 12 cm from the nipple. Mild posterior acoustic shadowing and peripheral vascularization (Figure 2bGo) was noted.


Figure 1
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  		Figure 1. Spot-view mammogram of the upper quadrant of the left breast shows a round dense mass with spiculated margins.

 

Figure 2
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  		Figure 2. (a,b) Granular cell tumour of the breast. (a) Sonogram reveals the complex pattern of the solid round mass, which has angular margins and a strong echogenic halo with the adjacent parenchyma. (b) Colour Doppler shows peripheral vascularization. Mild posterior acoustic shadowing can be observed.

 
Diagnostic bilateral breast MRI examination was performed with the patient prone in a 1.5 T commercially available system (Signa Excite; General Electric Medical Systems, Milwaukee, WI) using a dedicated surface breast coil. The imaging protocol includes a localizing sequence followed by an axial bilateral T1 weighted fast spin echo sequence (repetition time/echo time (TR/TE) = 800/8.9). A sagittal T1 weighted three-dimensional fat-suppressed fast spoiled gradient-echo sequence (TR/TE = 7.7/3.8) was then performed before, and three times after, a rapid bolus injection of 0.1 mmol L–1 of the gadolinium chelate gadodiamide (Omniscan; Amersham Health, UK) per kilogram of body weight delivered through an indwelling catheter, followed by a sagittal unilateral fat-suppressed T2 weighted sequence (TR/TE = 3700/125). The field of view and matrices were 22 cm and 320x192, respectively. Slice thickness was 3.8 mm with a 0 mm intersection gap. MR mammography revealed a 1.9 cm round-shaped mass (Figure 3aGo) with an irregular margin that was of low/intermediate signal on T1 weighted images. The lesion was not seen on a T2 weighted fat-suppressed sequence. Dynamic imaging revealed the lesion to be of low signal to breast parenchyma on pre-contrast sequence. Post-gadolinium (Gd-DTPA-BMA) enhancement imaging revealed a non-homogeneous lesion that showed mildly progressive rim enhancement (Figure 3bGo). The breast MRI was performed because mammographic and sonographic imaging features suggested malignancy to rule out multicentricity or multifocality.


Figure 3
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  		Figure 3. (a,b) MRI findings of granular cell tumour (GCT) of the breast. (a) Sagittal non-contrast T1weighted MR image shows a round mass with irregular margins presenting with low to intermediate signal intensity. (b) Sagittal subtracted contrast-enhanced T1weighted MR image shows the heterogeneously rim-enhancing mass.

 
Ultrasound-guided core biopsy using a 14-gauge automated needle was performed for histological diagnosis. Four cores were obtained, and histological assessment revealed a GCT (Figure 4Go). Nests of cells with abundant pink granular cytoplasm and small uniform nuclei extensively involved the cores of sampled tissue. Mitoses and nuclear pleomorphism were not present. A moderate lymphocytic infiltrate was seen. Immunohistochemistry showed the tumour cells to stain positively with S100, vimentin and CD68; the cells were negative for high and low molecular weight cytokeratins and carcino-embryonic antigen.


Figure 4
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  		Figure 4. Photomicrograph of core biopsy(haematoxylin and eosin) reveals nests of cells with abundant pink granular cytoplasm and small uniform nuclei extensively involved in the cores of sampled tissue (magnification x200).

 

   Discussion
Top
 Abstract
 Introduction
 Case description
 Discussion
References
 
GCT of the breast occurs in a wide range of ages, from teenagers to the elderly. An extensive review of the literature showed a slight preponderance in pre-menopausal black women [3–5]. The most common anatomical organ site of origin of GCTs is the tongue, followed by soft tissues. GCT of the breast accounts for only 5–8% of all GCTs reported [5]. These tumours occur more commonly in women; however, GCTs of the breast have been described in men [6, 7].

Clinically, these tumours present as a hard painless lump, which can mimic malignancy. Skin tethering can also be seen. Multiple (multifocal) lesions have been reported in 5.4% to 17.6% of cases [4, 5]. In contrast to most other breast tumours, which occur predominantly in the upper outer quadrant, GCTs are most frequently found in the upper inner quadrant [5], corresponding to the cutaneous sensory territory of the supraclavicular nerve. In our patient, the tumour was situated in the upper outer quadrant near the tail of Spencer. The largest imaging series of GCT of the breast published to date reported two cases located in the axillary tail but none in the upper inner quadrant [8].

Diagnostic imaging presentation of GCT of the breast is variable [3, 5–14]. These lesions have been described as ranging from a round well-circumscribed mass, to an indistinct or spiculated lesion on mammography. Microcalcifications are not usually a feature of GCTs. On ultrasound, GCTs can present as solid, poorly marginated lesions with marked posterior shadowing or as more benign-appearing well-circumscribed solid masses. Yang et al [8], who published sonographical and mammographical appearances of seven GCTs of the breast, reported an interesting observation: five out of seven (71%) lesions had either an echogenic halo or were partially hyperechoic. They attributed this to the infiltrative growth pattern of the GCTs. In our case, there was a mild acoustic shadowing, and an echogenic halo (a description concordant with many other authors) was present [7, 8, 13, 14].

There are few anecdotal reports on the MRI findings of GCT of the breast [10–12]. Kohashi et al [11] described the features as homogeneously enhancing masses on T1 weighted imaging that show a high signal intensity rim on T2 weighted sequence. Kuhl et al [15] reported that high T2 signal is a sign of benign disease; however, Bartella et al [16] showed a substantial percentage (24%) of invasive breast cancers as having high signal on T2 weighted imaging. Our case demonstrated GCT of the breast as a round mass with irregular margins that was slightly hypointense compared with the breast parenchyma on T1 weighted imaging, and which was not seen on T2 weighted imaging. After gadolinium injection, the enhancement was more pronounced in the periphery of the lesion. The visual analysis of the time-course of enhancement was categorized as persistent or showing increasing signal intensity throughout the dynamic period. However, on T2 weighted imaging, the lesion and the adjacent muscles had no associated signal. Most of the invasive cancers reported by Bartella et al [16] (61% of the invasive ductal carcinomas and 73% of the invasive lobular carcinomas) had no T2 signal.

We reviewed the MR findings of GCTs occurring at sites other than the breast (Table 1Go) [17–25]. The tumours' signal intensity present on T2 weighted images ranges from low to intermediate to high when compared with the adjacent muscles whereas, on T1 weighted images, it is low or intermediate in signal. In our case, the lesion was isointense to adjacent skeletal muscle on both T1 and T2 weighted imaging, and showed rim enhancement after gadolinium injection. Liberman et al [26] reported that the features with the highest likelihood for malignancy include spiculated margins, rim enhancement and irregular shape of breast masses. Rim enhancement had been described in GCTs occurring in sites other than the breast. Another interesting finding was the absence of any associated calcification component in all cases of GCTs reviewed. We assume that GCTs can be characteristically without calcification, but that the presence of calcifications in a mass should also make the possibility of GCT much less likely.


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  		Table 1. MR findings of granular cell tumour

 
Malignant GCTs are uncommon, but must be suspected when (i) pathologically enlarged lymph nodes are encountered in association with a tumour; (ii) the lesion is greater than 4 cm in diameter; (iii) there is heterogeneous signal intensity or rim enhancement; or (iv) there is infiltration of adjacent tissues [18, 20–21]. However, even benign GCTs can also have an infiltrating growth pattern, as was the case in our patient. There are no MRI-reported cases of malignant GCTs of the breast, and only a few reports of malignant breast cases have been published [27].

Clinically and radiographically, it is impossible to establish a definitive diagnosis of GCT of the breast without a biopsy. Sonographically guided percutaneous biopsy of the lesion is well established as the diagnostic procedure of choice for histopathology sampling [5, 8, 9, 13, 14]. Typically, GCT presents abundant granular eosinophilic cytoplasm on microscopy from which this tumour derives its name. Nests of polygonal cells with small, round, uniform and hyperchromatic nuclei are usually found. The antibodies used to confirm the diagnosis of GCT by immunohistochemistry are S100 and CD68. The detection of S100 protein expression may be needed to support the diagnosis, especially on small biopsies, when there is marked pseudoepitheliomatous hyperplasia mimicking squamous cell carcinoma, or to distinguish GCTs from other neoplasms with abundant eosinophilic granular cytoplasm [2]. The distinction between benign and malignant GCTs was proposed by Le et al and Adeniran et al [2, 5], and included the criteria of necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses per 10 HPF at x200 magnification), high nuclear/cytoplasmic ratio, and nuclear pleomorphism. These criteria classify GCT histologically into atypical (when two of these six criteria are present) and malignant (when three or more of these six criteria are met). However, malignant GCTs of the breast are rare in the literature [5, 27]. In our presented case, the description of the pathological features was supported by immunohistochemistry: S100 and CD68 were strongly expressed by the GCT and the negativity for carcino-embrionic antigen and cytokeratins ruled out an adenocarcinoma.

This case illustrates that, although GCT of the breast is a relatively rare breast neoplasm, it should be considered in the differential diagnosis of both radiologically benign and malignant lesions. Diagnostic work-up or follow-up should be made in accordance with the level of radiographical suspicion. Management of benign breast GCTs is largely dependent on the clinical presentation, and includes conservative follow-up or local excision. Local recurrence after adequate excision, although rare, has been reported in the male breast [7]. Malignant GCTs should be treated similarly to other breast malignant neoplasms. Breast MRI should be performed if the pathology results show malignancy. Pre-operative histological assessment of a breast lesion is therefore mandatory if conservative surgery and follow-up therapy is to be offered to patients.

Received for publication February 12, 2007. Revision received May 6, 2007. Accepted for publication May 27, 2007.


   References
Top
 Abstract
 Introduction
 Case description
 Discussion
 References
 

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