Clinical Review & Education
Clinical Problem Solving | PATHOLOGY
Thyroid Nodule Jennifer Prather, MD; Swati Mehrotra, MD
A
B
C
D
Figure. Histologic images of the left thyroid nodule. A and B, Hematoxylin-eosin, original magnification ×400; C, CD31 immunostain, original magnification ×200; D, pancytokeratin immunostain, original magnification ×200.
A man in his 60s with a history of hypertension, multinodular goiter, and colon cancer presented with a 5-month history of cough. After trials of antibiotics and inhaled steroids, the large goiter was suspected to be the cause of the cough. A 9-cm, left thyroid nodule was found, and the patient underwent left hemithyroidectomy. Because the patient presented from an outside hospital, it is not known if the nodule was previously sampled by fine-needle aspiration (FNA). Gross examination of the pathologic specimen revealed a 275-g, 9.5 × 8.0 × 5.0-cm hemithyroidectomy specimen. The cut surfaces were yellowish tan and hemorrhagic, with a small amount of
jamaotolaryngology.com
beefy red thyroid parenchyma. Approximately 50% of the mass consisted of soft, tan material in a cystic cavity. Histologically,thelesionhadareasoffibrosisandhemorrhagewith islands of hypercellularity. The hypercellular areas demonstrated 2 patterns: vascular (Figure, A) and solid sheets (Figure, B). The cells were large, with irregular nuclear membranes and prominent nucleoli. The cytoplasm was fluffy with frequent intracellular vacuoles, some of which contained red blood cells (Figure, B). Immunostains performed showed the tumor cells to be diffusely positive for CD31 (Figure, C) and focally positive for pancytokeratin (Figure, D). What is your diagnosis?
JAMA Otolaryngology–Head & Neck Surgery May 2014 Volume 140, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 05/29/2015
469
Clinical Review & Education Clinical Problem Solving
Diagnosis Primary thyroid angiosarcoma
Discussion Angiosarcoma is a rare soft-tissue tumor that can arise in nearly any site in the body.1 Men are affected more than women, with the seventh decade of life being the most common age of presentation. The most common site is the deep soft tissues.2 This malignant lesion is very aggressive, with a 5-year survival rate of 36%.3 Poor prognostic factors include advanced age, increased tumor size, retroperitoneal primary tumor, and increased proliferation index (>10%).2 Primary angiosarcoma of the thyroid can develop in a goiterous or a previously normal thyroid. The original case reports came from a region in the Swiss Alps where iodine deficiency and goiter were common.1,4 Thyroid angiosarcoma tends to spread rapidly, and patients have a median survival of 3.5 months.4,5 Patients with angiosarcoma present with a rapidly enlarging mass.4 Grossly, the mass is often large, with extensive hemorrhage. Histologically, the tumor forms sheets of spindled or epithelioid cells in a vasoformative or solid pattern. Cells have large, hyperchromatic nuclei, prominent nucleoli, and occasional intracytoplasmic lumen that may contain red blood cells. Numerous mitotic figures may be present.1,4,5 The tumor cells stain positively for CD31, CD34, and factor VIII—markers of vascular differentiation. Keratin staining is variable.1,4-6 Markers of thyroid follicular cell origin, such as TTF-1, thyroglobulin, and PAX-8, would be negative in angiosarcoma.7 The histologic differential diagnosis for vascular lesions in the thyroid includes a number of entities ranging from benign to malignant. 6 “Worrisome histologic alterations following fineneedle aspiration of the thyroid,” or WHAFFT, can be seen in thyroid resections. One study8 looked at 265 surgically excised thyroids that had been biopsied by FNA; 38.49% of cases showed ARTICLE INFORMATION Author Affiliations: Loyola University Medical Center, Maywood, Illinois. Corresponding Author: Swati Mehrotra, MD, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: March 20, 2014. doi:10.1001/jamaoto.2014.95.
2. Hart J, Mandavilli S. Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med. 2011;135(2):268-272. 3. National Cancer Institute. Cancer survival among adults. In: Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, eds. Sarcomas in SEER Survival Monograph: US SEER Program, 1988-2001, Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program; 2007. NIH Pub. No. 07-6215.
Conflict of Interest Disclosures: None reported.
4. Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd ed. Philadelphia, PA: Elsevier; 2007.
REFERENCES
5. Petronella P, Scorzelli M, Luise R, et al. Primary thyroid angiosarcoma: an unusual localization. World J Surg Oncol. 2012;10:73.
1. Isa NM, James DT, Saw TH, Pennisi R, Gough I. Primary angiosarcoma of the thyroid gland with recurrence diagnosed by fine needle aspiration: a case report. Diagn Cytopathol. 2009;37(6): 427-432.
470
FNA-associated changes, including hemorrhage, fibrosis, nuclear atypia, reactive vascular changes (including reactive endothelial hyperplasia), capsular pseudoinvasion, and metaplasia. Also included in the differential are the pseudoangiosarcomatous variant of medullary carcinoma and anaplastic or undifferentiated carcinoma. Medullary carcinoma of the thyroid can present with a number of different patterns. The pseudoangiomatous pattern results when cleftlike spaces form owing to cellular discohesion and hemorrhage filling the spaces can make the focus look vasoformative. Medullary carcinoma can be identified by positive results from immunohistochemical staining with calcitonin and chromogranin, which indicate origin from the neuroendocrine C cells of the thyroid.4,9 Anaplastic carcinoma should be included in the differential of any high-grade tumor of the thyroid. The bizarre cells and heterogeneous pattern of anaplastic carcinoma were not seen in our case.4 Also, staining for PAX-8, the only thyroid marker usually retained in anaplastic carcinoma, would be negative in angiosarcoma.7 Treatment for angiosarcoma is similar across all sites. Resection, followed by chemotherapy and radiation, is used but is often unsuccessful.5 Unfortunately, even with treatment, the prognosis is poor. The patient described herein developed massive hemoptysis a few weeks after his thyroid resection. Multiple lung lesions and pleural fluid involvement by angiosarcoma were found. He died shortly thereafter. In summary, angiosarcoma is an aggressive soft-tissue tumor that can develop in nearly any site of the body, but rarely in the thyroid. Tumor histologic findings demonstrate atypical spindled or epithelioid cells with vasoformative or solid architecture. In the thyroid, the differential diagnosis of vascular lesions includes benign entities, such as WHAFFT, an entity that can cause diagnostic confusion in the setting of previously biopsied lesions. A variety of diagnoses of malignant disease can also be considered, including angiosarcoma, as described in this case. 7. Bishop JA, Sharma R, Westra WH. PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol. 2011;42(12):1873-1877. 8. Pandit AA, Phulpagar MD. Worrisome histologic alterations following fine needle aspiration of the thyroid. Acta Cytol. 2001;45(2):173-179. 9. Laforga JB, Aranda FI. Pseudoangiosarcomatous features in medullary thyroid carcinoma spindle-cell variant: report of a case studied by FNA and immunohistochemistry. Diagn Cytopathol. 2007;35(7):424-428.
6. Papotti M, Arrondini M, Tavaglione V, Veltri A, Volante M. Diagnostic controversies in vascular proliferations of the thyroid gland. Endocr Pathol. 2008;19(3):175-183.
JAMA Otolaryngology–Head & Neck Surgery May 2014 Volume 140, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 05/29/2015
jamaotolaryngology.com
Clinical Problem Solving | PATHOLOGY
Thyroid Nodule Jennifer Prather, MD; Swati Mehrotra, MD
A
B
C
D
Figure. Histologic images of the left thyroid nodule. A and B, Hematoxylin-eosin, original magnification ×400; C, CD31 immunostain, original magnification ×200; D, pancytokeratin immunostain, original magnification ×200.
A man in his 60s with a history of hypertension, multinodular goiter, and colon cancer presented with a 5-month history of cough. After trials of antibiotics and inhaled steroids, the large goiter was suspected to be the cause of the cough. A 9-cm, left thyroid nodule was found, and the patient underwent left hemithyroidectomy. Because the patient presented from an outside hospital, it is not known if the nodule was previously sampled by fine-needle aspiration (FNA). Gross examination of the pathologic specimen revealed a 275-g, 9.5 × 8.0 × 5.0-cm hemithyroidectomy specimen. The cut surfaces were yellowish tan and hemorrhagic, with a small amount of
jamaotolaryngology.com
beefy red thyroid parenchyma. Approximately 50% of the mass consisted of soft, tan material in a cystic cavity. Histologically,thelesionhadareasoffibrosisandhemorrhagewith islands of hypercellularity. The hypercellular areas demonstrated 2 patterns: vascular (Figure, A) and solid sheets (Figure, B). The cells were large, with irregular nuclear membranes and prominent nucleoli. The cytoplasm was fluffy with frequent intracellular vacuoles, some of which contained red blood cells (Figure, B). Immunostains performed showed the tumor cells to be diffusely positive for CD31 (Figure, C) and focally positive for pancytokeratin (Figure, D). What is your diagnosis?
JAMA Otolaryngology–Head & Neck Surgery May 2014 Volume 140, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 05/29/2015
469
Clinical Review & Education Clinical Problem Solving
Diagnosis Primary thyroid angiosarcoma
Discussion Angiosarcoma is a rare soft-tissue tumor that can arise in nearly any site in the body.1 Men are affected more than women, with the seventh decade of life being the most common age of presentation. The most common site is the deep soft tissues.2 This malignant lesion is very aggressive, with a 5-year survival rate of 36%.3 Poor prognostic factors include advanced age, increased tumor size, retroperitoneal primary tumor, and increased proliferation index (>10%).2 Primary angiosarcoma of the thyroid can develop in a goiterous or a previously normal thyroid. The original case reports came from a region in the Swiss Alps where iodine deficiency and goiter were common.1,4 Thyroid angiosarcoma tends to spread rapidly, and patients have a median survival of 3.5 months.4,5 Patients with angiosarcoma present with a rapidly enlarging mass.4 Grossly, the mass is often large, with extensive hemorrhage. Histologically, the tumor forms sheets of spindled or epithelioid cells in a vasoformative or solid pattern. Cells have large, hyperchromatic nuclei, prominent nucleoli, and occasional intracytoplasmic lumen that may contain red blood cells. Numerous mitotic figures may be present.1,4,5 The tumor cells stain positively for CD31, CD34, and factor VIII—markers of vascular differentiation. Keratin staining is variable.1,4-6 Markers of thyroid follicular cell origin, such as TTF-1, thyroglobulin, and PAX-8, would be negative in angiosarcoma.7 The histologic differential diagnosis for vascular lesions in the thyroid includes a number of entities ranging from benign to malignant. 6 “Worrisome histologic alterations following fineneedle aspiration of the thyroid,” or WHAFFT, can be seen in thyroid resections. One study8 looked at 265 surgically excised thyroids that had been biopsied by FNA; 38.49% of cases showed ARTICLE INFORMATION Author Affiliations: Loyola University Medical Center, Maywood, Illinois. Corresponding Author: Swati Mehrotra, MD, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153 ([email protected]). Section Editor: Edward B. Stelow, MD. Published Online: March 20, 2014. doi:10.1001/jamaoto.2014.95.
2. Hart J, Mandavilli S. Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med. 2011;135(2):268-272. 3. National Cancer Institute. Cancer survival among adults. In: Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J, eds. Sarcomas in SEER Survival Monograph: US SEER Program, 1988-2001, Patient and Tumor Characteristics. Bethesda, MD: National Cancer Institute, SEER Program; 2007. NIH Pub. No. 07-6215.
Conflict of Interest Disclosures: None reported.
4. Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 3rd ed. Philadelphia, PA: Elsevier; 2007.
REFERENCES
5. Petronella P, Scorzelli M, Luise R, et al. Primary thyroid angiosarcoma: an unusual localization. World J Surg Oncol. 2012;10:73.
1. Isa NM, James DT, Saw TH, Pennisi R, Gough I. Primary angiosarcoma of the thyroid gland with recurrence diagnosed by fine needle aspiration: a case report. Diagn Cytopathol. 2009;37(6): 427-432.
470
FNA-associated changes, including hemorrhage, fibrosis, nuclear atypia, reactive vascular changes (including reactive endothelial hyperplasia), capsular pseudoinvasion, and metaplasia. Also included in the differential are the pseudoangiosarcomatous variant of medullary carcinoma and anaplastic or undifferentiated carcinoma. Medullary carcinoma of the thyroid can present with a number of different patterns. The pseudoangiomatous pattern results when cleftlike spaces form owing to cellular discohesion and hemorrhage filling the spaces can make the focus look vasoformative. Medullary carcinoma can be identified by positive results from immunohistochemical staining with calcitonin and chromogranin, which indicate origin from the neuroendocrine C cells of the thyroid.4,9 Anaplastic carcinoma should be included in the differential of any high-grade tumor of the thyroid. The bizarre cells and heterogeneous pattern of anaplastic carcinoma were not seen in our case.4 Also, staining for PAX-8, the only thyroid marker usually retained in anaplastic carcinoma, would be negative in angiosarcoma.7 Treatment for angiosarcoma is similar across all sites. Resection, followed by chemotherapy and radiation, is used but is often unsuccessful.5 Unfortunately, even with treatment, the prognosis is poor. The patient described herein developed massive hemoptysis a few weeks after his thyroid resection. Multiple lung lesions and pleural fluid involvement by angiosarcoma were found. He died shortly thereafter. In summary, angiosarcoma is an aggressive soft-tissue tumor that can develop in nearly any site of the body, but rarely in the thyroid. Tumor histologic findings demonstrate atypical spindled or epithelioid cells with vasoformative or solid architecture. In the thyroid, the differential diagnosis of vascular lesions includes benign entities, such as WHAFFT, an entity that can cause diagnostic confusion in the setting of previously biopsied lesions. A variety of diagnoses of malignant disease can also be considered, including angiosarcoma, as described in this case. 7. Bishop JA, Sharma R, Westra WH. PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol. 2011;42(12):1873-1877. 8. Pandit AA, Phulpagar MD. Worrisome histologic alterations following fine needle aspiration of the thyroid. Acta Cytol. 2001;45(2):173-179. 9. Laforga JB, Aranda FI. Pseudoangiosarcomatous features in medullary thyroid carcinoma spindle-cell variant: report of a case studied by FNA and immunohistochemistry. Diagn Cytopathol. 2007;35(7):424-428.
6. Papotti M, Arrondini M, Tavaglione V, Veltri A, Volante M. Diagnostic controversies in vascular proliferations of the thyroid gland. Endocr Pathol. 2008;19(3):175-183.
JAMA Otolaryngology–Head & Neck Surgery May 2014 Volume 140, Number 5
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archotol.jamanetwork.com/ by a J H Quillen College User on 05/29/2015
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