Fine Needle Aspiration Cytology of a Myoepithelioma Presenting as a Thyroid Nodule Christina Narick, M.D.,1 Claudia Velosa, M.D.,1 Philip Pollice, M.D.,2 and Jan Silverman, M.D.1*
Myoepitheliomas are rare neoplasms that are typically found in the major and minor salivary glands and represent approximately 1.5% of all salivary gland neoplasms. We present a patient with an exophytic anterior midline neck mass, which was initially believed to be a thyroid isthmus nodule that underwent fine needle aspiration (FNA) biopsy. FNA cytologic evaluation reveals numerous plump spindle cells and a myxoid background, thus raising the possibility of rare benign mixed tumor of the thyroid. However, the resected specimen consists of predominately spindle cells with a minor component of chondromyxoid matrix, and no ductal epithelial cells, favoring a diagnosis of myoepithelioma. Although this lesion clinically and radiologically appeared to arise from the thyroid gland, at the time of resection, it was found to be adjacent to the thyroid isthmus and was ultimately diagnosed as a soft tissue myoepithelioma of the midneck. Diagn. Cytopathol. 2015;43:153–157. VC 2014 Wiley
and mixed tumors are on the spectrum of tumor showing myoepithelial differentiation. Histologically, myoepitheliomas are composed of myoepithelial cells showing epithelioid, plasmacytoid, clear cell, and/or spindle cell morphology in a myxoid or fibrous stroma.2 Distinction from pleomorphic adenoma is based on the relative lack of ducts and absence of myxochondroid or chondroid areas.1 We report a case of a soft tissue myoepithelioma that are presented as an enlarging anterior neck mass, which clinically and radiologically appeared to arise from the thyroid gland.
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This patient is a 41-year-old female who presented with a palpable slowly enlarging anterior neck mass that had been initially identified approximately 4 years earlier. A computerized tomography scan demonstrated a 2.8 3 2.4 3 1.2 cm mass embedded within the strap muscles, and contiguous with the superior surface of the thyroid isthmus (Fig. 1). This imaging study, further, described the mass as heterogeneous in appearance with the superior margin inferior to the hyoid and the posterior surface abutting the thyroid cartilage. The radiographic differential diagnosis includes a thyroid neoplasm, an exophytic thyroid nodule extending from the isthmus, or a neoplasm arising from the strap muscles, such as sarcoma. A subsequent ultrasound examination demonstrated a 2.8 3 2.4 3 1.2 cm lobulated complex heterogeneous hypoechoic midline lesion. The mass underwent fine needle aspiration (FNA) biopsy using both 23 and 25 gauge needles yielding direct smears for both Diff–Quik (Fig. 2) and Papanicolaou staining (Fig. 3). The smears were highly cellular with plump spindle-shaped cells, evident as both single cells and aggregates, some of which were embedded in magenta matrix material seen best on Diff–Quik stain. A panel of immunohistochemical (IHC) studies performed on the cell block revealed positive staining for cytokeratins (CAM 5.2, AE 1/3, CK5/6), p63 and HHF35
Key Words: tumor
myoepithelioma; thyroid nodule; benign mixed
Introduction Myoepithelioma is a well-defined entity in the salivary gland, accounting for 1.5% of neoplasms in the major and minor salivary glands.1 Soft tissue myoepithelioma is a rare recently described neoplasm, occurs equally in adult males and females, with a wide age range peaking in the third to fifth decades,2 is most commonly found in the limbs and limb girdles3 with less than 15% occurring in the head and neck region.1 Soft tissue myoepitheliomas 1 Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania 2 Metropolitan Ear, Nose & Throat Associates, UPMC, Wexford, Pennsylvania *Correspondence to: J. Silverman, M.D., Department of Pathology and Laboratory Medicine, Allegheny General Hospital, 320 E. North Avenue, Pittsburgh PA 15212. E-mail: [email protected] Received 11 December 2013; Accepted 18 March 2014 DOI: 10.1002/dc.23161 Published online 3 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
Case Report
Diagnostic Cytopathology, Vol. 43, No 2
153
Diagnostic Cytopathology DOI 10.1002/dc
NARICK ET AL.
Fig. 1. Computerized tomography scan demonstrating midline anterior neck lesion.
Fig. 3. FNA cytology smears of nodule, Papanicolaou stain; (a) spindle cells and matrix material (2003), (b) uniform plump spindle cells (4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 2. FNA cytology smears of nodule, Diff–Quik stain; (a) uniform plump spindle cells (2003), (b) highly cellular specimen with magenta matrix material (arrows) (2003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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supportive for diagnosis of a rare benign mixed tumor of the thyroid (Fig. 4). The IHC markers for medullary carcinoma including synaptophysin, chromogranin, TTF-1, PAX-8, and calcitonin were negative. The patient then underwent an excisional biopsy of this mass with thyroid isthmusectomy. At the time of surgery, the mass was found embedded within the strap muscles and appeared to be attached to the thyroid isthmus. Thyroid isthmusectomy was performed. The gross specimen consisted of a firm encapsulated mass with a smooth glistening surface, and attached muscle and fibrous tissue. The sectioned surface was white and nodular, with adjacent dark red thyroid parenchyma. Histologic examination of the hematoxylin and eosin (H&E) slides correlated well with cytology showing an encapsulated lesion abutting, but not infiltrating the adjacent thyroid parenchyma (Fig. 5). The lesion consisted of predominantly uniform bland spindle cells with fine even chromatin and inconspicuous nucleoli arranged in a somewhat nodular pattern with transversing fibrous bands. A
Diagnostic Cytopathology DOI 10.1002/dc
MYOEPITHELIOMA, THYROID, HEAD, AND NECK
Fig. 5. Resected mass (right) abuts but does not invade adjacent thyroid parenchyma (left), (H&E, 1003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
The differential diagnosis of this spindle cell lesion included myoepithelioma, myoepithelial rich mixed tumor (pleomorphic adenoma), myoepithelial carcinoma, nerve sheath tumor, and tumors of smooth muscle origin. An extensive panel of IHC stains was applied to further characterize this lesion. The neoplastic cells were strongly positive for cytokeratins (CAM 5.2, AE 1/3, and CK 5/6), and demonstrated strong nuclear staining for p63. Additional positive markers included epithelial membrane antigen, glial fibrillary acidic protein, MAP-2, CD56, vimentin, smooth muscle myosin heavy chain, calponin, smooth muscle actin, BCL-2, and CD99. Tumor cells demonstrated only focal positivity for HHF-35. The cell morphology, architectural pattern, and IHC profile support diagnosis of a myoepithelial neoplasm favoring myoepithelioma. Although thyroid tissue was found adjacent to this lesion, there was no microscopic evidence that this neoplasm arose from the thyroid tissue. The final diagnosis was soft tissue myoepithelioma adjacent to the thyroid isthmus. All margins were free of tumor. Fig. 4. (a) cell block demonstrating spindle cells and chondromyxoid matrix (Diff–Quik, 2003), (b) CAM 5.2 strong diffuse positivity (2003), (c) P63 strong nuclear staining pattern (2003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
slight amount of chondromyxoid matrix material was evident in the background, and there were foci of rounded epitheliod cells, some with cytoplasmic vacuolization (Fig. 6), however, no definite ductal cells were identified. Areas of epitheliod cells forming microcystic spaces with eosinophilic material were identified as well as squamous metaplasia. The mitotic activity was noted to be very low overall, although few fields showed mitotic activity of 3–4 mitoses/high power field.
Discussion Benign mixed tumors comprise approximately 60% of all salivary gland neoplasms with a reported incidence of 2.4– 3.0 per 100,000 population.1 In contrast, myoepitheliomas consisting of predominately myoepithelial cells are quite rare, representing only 1.5% of all salivary gland tumors.1,4 Myoepitheliomas have been previously described in the larynx,5 the vallecula,6 the auditory canal, skin,7 and multiple soft tissue locations.3,7 However, this entity has not yet been reported in the midline anterior neck. Some authors contend that the presence or absence of both the chondromyxoid background matrix and epithelial cells can be used to separate benign mixed tumor from myoepithelioma,1,8 while others maintain that these two entities are separated by the minimum (
Myoepitheliomas are rare neoplasms that are typically found in the major and minor salivary glands and represent approximately 1.5% of all salivary gland neoplasms. We present a patient with an exophytic anterior midline neck mass, which was initially believed to be a thyroid isthmus nodule that underwent fine needle aspiration (FNA) biopsy. FNA cytologic evaluation reveals numerous plump spindle cells and a myxoid background, thus raising the possibility of rare benign mixed tumor of the thyroid. However, the resected specimen consists of predominately spindle cells with a minor component of chondromyxoid matrix, and no ductal epithelial cells, favoring a diagnosis of myoepithelioma. Although this lesion clinically and radiologically appeared to arise from the thyroid gland, at the time of resection, it was found to be adjacent to the thyroid isthmus and was ultimately diagnosed as a soft tissue myoepithelioma of the midneck. Diagn. Cytopathol. 2015;43:153–157. VC 2014 Wiley
and mixed tumors are on the spectrum of tumor showing myoepithelial differentiation. Histologically, myoepitheliomas are composed of myoepithelial cells showing epithelioid, plasmacytoid, clear cell, and/or spindle cell morphology in a myxoid or fibrous stroma.2 Distinction from pleomorphic adenoma is based on the relative lack of ducts and absence of myxochondroid or chondroid areas.1 We report a case of a soft tissue myoepithelioma that are presented as an enlarging anterior neck mass, which clinically and radiologically appeared to arise from the thyroid gland.
Periodicals, Inc.
This patient is a 41-year-old female who presented with a palpable slowly enlarging anterior neck mass that had been initially identified approximately 4 years earlier. A computerized tomography scan demonstrated a 2.8 3 2.4 3 1.2 cm mass embedded within the strap muscles, and contiguous with the superior surface of the thyroid isthmus (Fig. 1). This imaging study, further, described the mass as heterogeneous in appearance with the superior margin inferior to the hyoid and the posterior surface abutting the thyroid cartilage. The radiographic differential diagnosis includes a thyroid neoplasm, an exophytic thyroid nodule extending from the isthmus, or a neoplasm arising from the strap muscles, such as sarcoma. A subsequent ultrasound examination demonstrated a 2.8 3 2.4 3 1.2 cm lobulated complex heterogeneous hypoechoic midline lesion. The mass underwent fine needle aspiration (FNA) biopsy using both 23 and 25 gauge needles yielding direct smears for both Diff–Quik (Fig. 2) and Papanicolaou staining (Fig. 3). The smears were highly cellular with plump spindle-shaped cells, evident as both single cells and aggregates, some of which were embedded in magenta matrix material seen best on Diff–Quik stain. A panel of immunohistochemical (IHC) studies performed on the cell block revealed positive staining for cytokeratins (CAM 5.2, AE 1/3, CK5/6), p63 and HHF35
Key Words: tumor
myoepithelioma; thyroid nodule; benign mixed
Introduction Myoepithelioma is a well-defined entity in the salivary gland, accounting for 1.5% of neoplasms in the major and minor salivary glands.1 Soft tissue myoepithelioma is a rare recently described neoplasm, occurs equally in adult males and females, with a wide age range peaking in the third to fifth decades,2 is most commonly found in the limbs and limb girdles3 with less than 15% occurring in the head and neck region.1 Soft tissue myoepitheliomas 1 Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania 2 Metropolitan Ear, Nose & Throat Associates, UPMC, Wexford, Pennsylvania *Correspondence to: J. Silverman, M.D., Department of Pathology and Laboratory Medicine, Allegheny General Hospital, 320 E. North Avenue, Pittsburgh PA 15212. E-mail: [email protected] Received 11 December 2013; Accepted 18 March 2014 DOI: 10.1002/dc.23161 Published online 3 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
C 2014 WILEY PERIODICALS, INC. V
Case Report
Diagnostic Cytopathology, Vol. 43, No 2
153
Diagnostic Cytopathology DOI 10.1002/dc
NARICK ET AL.
Fig. 1. Computerized tomography scan demonstrating midline anterior neck lesion.
Fig. 3. FNA cytology smears of nodule, Papanicolaou stain; (a) spindle cells and matrix material (2003), (b) uniform plump spindle cells (4003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 2. FNA cytology smears of nodule, Diff–Quik stain; (a) uniform plump spindle cells (2003), (b) highly cellular specimen with magenta matrix material (arrows) (2003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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supportive for diagnosis of a rare benign mixed tumor of the thyroid (Fig. 4). The IHC markers for medullary carcinoma including synaptophysin, chromogranin, TTF-1, PAX-8, and calcitonin were negative. The patient then underwent an excisional biopsy of this mass with thyroid isthmusectomy. At the time of surgery, the mass was found embedded within the strap muscles and appeared to be attached to the thyroid isthmus. Thyroid isthmusectomy was performed. The gross specimen consisted of a firm encapsulated mass with a smooth glistening surface, and attached muscle and fibrous tissue. The sectioned surface was white and nodular, with adjacent dark red thyroid parenchyma. Histologic examination of the hematoxylin and eosin (H&E) slides correlated well with cytology showing an encapsulated lesion abutting, but not infiltrating the adjacent thyroid parenchyma (Fig. 5). The lesion consisted of predominantly uniform bland spindle cells with fine even chromatin and inconspicuous nucleoli arranged in a somewhat nodular pattern with transversing fibrous bands. A
Diagnostic Cytopathology DOI 10.1002/dc
MYOEPITHELIOMA, THYROID, HEAD, AND NECK
Fig. 5. Resected mass (right) abuts but does not invade adjacent thyroid parenchyma (left), (H&E, 1003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
The differential diagnosis of this spindle cell lesion included myoepithelioma, myoepithelial rich mixed tumor (pleomorphic adenoma), myoepithelial carcinoma, nerve sheath tumor, and tumors of smooth muscle origin. An extensive panel of IHC stains was applied to further characterize this lesion. The neoplastic cells were strongly positive for cytokeratins (CAM 5.2, AE 1/3, and CK 5/6), and demonstrated strong nuclear staining for p63. Additional positive markers included epithelial membrane antigen, glial fibrillary acidic protein, MAP-2, CD56, vimentin, smooth muscle myosin heavy chain, calponin, smooth muscle actin, BCL-2, and CD99. Tumor cells demonstrated only focal positivity for HHF-35. The cell morphology, architectural pattern, and IHC profile support diagnosis of a myoepithelial neoplasm favoring myoepithelioma. Although thyroid tissue was found adjacent to this lesion, there was no microscopic evidence that this neoplasm arose from the thyroid tissue. The final diagnosis was soft tissue myoepithelioma adjacent to the thyroid isthmus. All margins were free of tumor. Fig. 4. (a) cell block demonstrating spindle cells and chondromyxoid matrix (Diff–Quik, 2003), (b) CAM 5.2 strong diffuse positivity (2003), (c) P63 strong nuclear staining pattern (2003). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
slight amount of chondromyxoid matrix material was evident in the background, and there were foci of rounded epitheliod cells, some with cytoplasmic vacuolization (Fig. 6), however, no definite ductal cells were identified. Areas of epitheliod cells forming microcystic spaces with eosinophilic material were identified as well as squamous metaplasia. The mitotic activity was noted to be very low overall, although few fields showed mitotic activity of 3–4 mitoses/high power field.
Discussion Benign mixed tumors comprise approximately 60% of all salivary gland neoplasms with a reported incidence of 2.4– 3.0 per 100,000 population.1 In contrast, myoepitheliomas consisting of predominately myoepithelial cells are quite rare, representing only 1.5% of all salivary gland tumors.1,4 Myoepitheliomas have been previously described in the larynx,5 the vallecula,6 the auditory canal, skin,7 and multiple soft tissue locations.3,7 However, this entity has not yet been reported in the midline anterior neck. Some authors contend that the presence or absence of both the chondromyxoid background matrix and epithelial cells can be used to separate benign mixed tumor from myoepithelioma,1,8 while others maintain that these two entities are separated by the minimum (
