Case 4 -
Oxyphilic Nodule, with Cystic Changes
Mary K. Sidawy
The George Washington University
Click on each slide thumbnail image for an enlarged view
A 65-year-old woman referred for FNA of bilateral thyroid nodules
which were discovered during a routine physical examination. A thyroid scan showed bilateral cold
nodules. The patient had a history of systemic lupus erythematosus, and ductal carcinoma in situ of the right breast that was treated with a mastectomy. Physical
examination revealed a firm 1.5 cm left lower pole nodule, and a softer 2.5 cm nodule in right lobe of
the thyroid. Both nodules moved up and down with swallowing. Aspirate of the right lobe revealed
oxyphilic follicular cells and colloid. The FNA of the left nodule is illustrated (Figures A,B,C).
Case 4 - Figure A - Aspiration of the left lower lobe nodule yielded cohesive large sheet of crowded neoplastic cells. The cells smeared poorly and crush artifact is prominent. Colloid is absent from the background. A polymorphous lymphoid infiltrate is focally appreciated, elsewhere in the smear (Diff-Quik stain, low power).
Case 4 - Figure B - Higher power image shows neoplastic cells with small, elongated nuclei. Poor preservation due to crush artifact is a prominent finding in this case (Diff-Quik stain, medium power).
Case 4 - Figure C - High power image shows focal "nested" appearance reminiscent of a microfollicular or acinar arrangement. No mitotic figures or necrosis present (Diff-Quik stain, high power).
Aspiration of the left lobe yielded cohesive sheets
and clusters of crowded epithelial cells. The cells were small, had bland ovoid nuclei, scant cytoplasm
with indistinct cell borders, and were focally arranged in a nesting pattern. Lymphoid tangles (crushed
lymphocytes) small lymphocytes , and few activated lymphocytes were seen in the background. Colloid was
absent. Immunoperoxidase stains, performed on the Thin-Prep preparations, showed the neoplastic cells to
be positive for epithelial markers (CAM-2) and negative for neurone-specific enolase, calcitonin and
thyroglobulin. The lymphoid cells were positive for leucocyte common antigen. The left lobe nodule was
interpreted as "Thyroid neoplasm not further classified and Hashimoto's thyroiditis." Surgical excision
for a definite classification was recommended.
The FNA of the right lobe nodule was cellular and composed of oxyphilic follicular cells arranged
singly, in groups and sheets. Foamy and hemosiderin-laden histiocytes, and colloid were also noted. A
cytologic diagnosis of "Oxyphilic nodule, with cystic changes" was rendered.
History and Surgical Follow-up
A preoperative chest x-ray showed a 4 cm soft tissue mass in the thoracic inlet with right-sided
tracheal deviation, probably representing thyroid enlargement. A total thyroidectomy and excision of the
left inferior pole mass were performed. What clinically appeared to be 1.5 cm firm nodule in the left
lower pole was found to actually represent the superior tip of a larger substernal mass that extended
under the clavicle into the mediastinum.
Grossly, the left lobe of thyroid showed multiple colloid cysts, and attached to its inferior pole was
a 5 X 3.5 cm encapsulated mass with a tan homogeneous-cut surface. The right lobe showed a 2 X 1.8 cm
partially cystic lesion occupying most of the lobe.
Microscopic sections of the mass attached to the left inferior pole revealed a neoplasm surrounded by
a thick fibrous capsule. Thick fibrous bands dividing the tumor into lobules were also noted. The
neoplasm was composed of sheets and whorls of cytologically bland appearing, focally spindled, epithelial
cells. Mature lymphocytes were scattered throughout the neoplasm. Fibrosis and few nests of tumor cells
were noted in perithyroidal soft tissue and fat. However, no involvement of the thyroid parenchyma was
noted. The diagnosis of thymoma with penetration of perithyroidal tissue
Microscopic sections of the right lobe of thyroid nodule showed an encapsulated neoplasm composed of
large oxyphilic cells with mild nuclear pleomorphism. No vascular invasion or capsular penetration was
noted. The diagnosis of a benign Hurthle cell nodule consistent with adenoma was rendered.
Thymoma is the most common primary neoplasm in the anterosuperior mediastinum. The cytopathologic
characteristics of thymoma consist of a 'biphasic pattern' or 'dual population' of epithelial cells and
lymphocytes. The degree of cellular cohesion of the epithelial cells varies. The epithelial component
may consist of spindle cells with elongated regular nuclei and inconspicuous nuclei. The cytoplasm of
the epithelial cells is scant to moderate, with indistinct borders. The nuclei are bland with smooth
nuclear outline, pale, finely granular chromatin. The proportion of epithelial and lymphoid cells
varies and may lead to the erroneous diagnosis of metastatic carcinoma when the lymphoid component is
sparse, while the predominance of lymphoid cells may simulate a lymphoma.
Preoperative FNA of thymoma mimicking a thyroid lesion has been reported. Most reported cases were
misdiagnosed. Lymphocytic thyroiditis, malignant lymphoma, and a neoplasm, not further classified, are
the most common rendered diagnoses.
The FNA of the left lobe nodule clearly demonstrated a dual population of neoplastic epithelial cells
and a polymorphous lymphoid population. The presence of the latter in conjunction with the presence of
an oxyphilic nodule in the right lobe led us to conclude that the lymphoid component was part of
Immunostains were performed in an attempt to classify this unusual epithelial neoplasm characterized
by nests of bland, small spindled cells. We excluded follicular neoplasm and papillary carcinoma based
on the above cytologic features, the absence of follicular or papillary pattern, the lack of colloid and
the negative thyroglobulin immunostain. Medullary carcinoma was considered because of the spindled
nature of the neoplastic cells, but was not supported by the negative calcitonin and neurone-specific
enolase stains, and lack of amyloid. The small size of the cells and the nesting pattern suggested an
insular carcinoma, but evidence of malignancy, such as necrotic background and mitoses, as well as
microfollicles, trabeculae and positive staining for thyroglobulin, were not seen. The following
summarizes the cytologic criteria and clues of the entities considered in the differential diagnosis of
small spindle cell lesion of the thyroid:
Hyalinizing trabecular adenoma
| Smears are cellular, cells occur in aggregates or as single cells.|
| Nuclei are slightly enlarged, oval to spindle with pale chromatin.|
| Intranuclear inclusions.|
| Longitudinal grooving of nuclear membrane.|
| Air-dried smears reveal a distinctive purple stromal deposits.|
| Central core of amorphous hyaline material surrounded by follicular cells.|
| The clue to recognizing hyalinizing trabecular adenoma cytologically, is the combination of features of both papillary and medullary carcinoma.|
| Negative Congo red and calcitonin immunostain should assist in excluding the diagnosis of medullary carcinoma.|
| Smears reveal abundant cellularity.|
| Cells are isolated or in loose fragments.|
| Plasmacytoid, spindle-shaped, or small round cells.|
| Cytoplasm finely granular - Pink cytoplasmic granules is a characteristic feature in air-dried Diff-Quik-stained preparations.|
| Variable degree of nuclear pleomorphism.|
| Bi- or multinucleation very common.|
| Intranuclear cytoplasmic inclusions.|
| Chromatin displays neuroendocrine features.|
| Presence of amyloid (amorphous, acellular material).|
| Positive for calcitonin and chromogranin.|
| Neurosecretory granules by electron microscopy.|
Anaplastic (undifferentiated) carcinoma
| The cytologic features reveal a wide variation.|
| Bizarre cells with unequivocal features of malignancy.|
| Cells are isolated or in loose groups.|
| Spindle and polygonal cells.|
| Nuclei hyperchromatic with clumped chromatin.|
| Osteoclast-like giant cells.|
| Mitotic figures.|
| Obtaining diagnostic material is occasionally difficult because of extensive fibrosis or necrosis.|
Poorly differentiated "insular" carcinoma
| High cellularity.|
| Scant colloid.|
| Relatively uniform tumor cells in clusters, trabeculae, microfollicular or a single cell pattern.|
| Poorly outlined cytoplasm.|
| Nuclei hyperchromatic with occasional nucleoli.|
| Mitoses and a necrotic background.|
Non-thyroid malignant tumors may also present as thyroid nodules. The most common neoplasms
metastasizing to the thyroid, are carcinomas of the lung, the gastrointestinal tract, breast and
melanomas. In these instances, awareness of the history, immunocytochemistry, and comparing the aspirate
with the intraoperative smears and/or histological sections of the pervious surgical specimen should aid
in reaching the correct diagnosis. In our case, given the history of breast carcinoma, albeit in situ, a metastatic breast carcinoma was considered, but the lack of single
cells and significant cytologic atypia milited against this diagnosis.
In conclusion, thymoma may present as a palpable neck mass that clinically mimics a thyroid nodule.
The possibility of thymoma should be considered when the FNA of a neck mass reveals a dual population of
lymphoid and epithelial cells. Awareness of this entity and the constellation of the characteristic
cytologic features can prevent a misdiagnosis of this well-recognized pitfall.
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