Anaplastic (Undifferentiated) Thyroid Carcinoma

Laryngeal Squamous Cell Carcinoma Involving Thyroid Gland

Age

Typically elderly adults, peak in seventh decade. Rare in patients younger than 50. Female predominance

Adults, peak sixth to seventh decades, male predominance

Location

Thyroid gland, often with extension into surrounding soft tissues including the larynx

In the larynx, most common in the glottis followed by the supraglottis and subglottis. High-stage cancers may invade the thyroid gland

Symptoms

Rapidly enlarging neck mass, often with dyspnea, dysphagia, and hoarseness

Hoarseness, dysphonia, dysphagia, and pain

Signs

Large, firm, nodular thyroid mass, often with extension into soft tissues of the neck. Lymphadenopathy with or without distant metastases is common

Variably exophytic or endophytic mass, often ulcerated

Etiology

Most anaplastic carcinomas arise from welldifferentiated thyroid carcinomas (e.g., follicular and papillary carcinomas)

Associated with smoking

Histology

1. 
   

   Highly infiltrative often with vascular invasion and invasion of adjacent structures including the larynx (Fig. 9.1.1)

   
   
2. 
   

   Three histologic patterns, which can coexist in varying proportions in the same tumor: squamoid, spindle cell, and giant cell (Figs. 9.1.2 and 9.1.3). The squamoid variant is most likely to be confused with squamous cell carcinoma of the larynx

   
   
3. 
   

   The squamoid variant is usually nonkeratinizing. Keratin pearls are uncommon

   
   
4. 
   

   Dysplasia/squamous cell carcinoma in situ of the laryngeal surface is not present

   
   
5. 
   

   Anaplastic carcinoma often arises in association with a differentiated thyroid carcinoma, either papillary carcinoma or follicular carcinoma (Fig. 9.1.4)

   
   
6. 
   

   Frequently accompanied by an inflammatory infiltrate, especially neutrophils

1. 
   

   Highly infiltrative tumor that may invade nearby structures including thyroid gland (Fig. 9.1.6)

   
   
2. 
   

   Purely squamous histology, usually without spindle cell or giant cell patterns (except in sarcomatoid variant)

   
   
3. 
   

   Often keratinizing. Keratin pearls are common (Fig. 9.1.7)

   
   
4. 
   

   An in situ component of the laryngeal surface epithelium is often seen (Fig. 9.1.8)

   
   
5. 
   

   Does not show an association with a differentiated thyroid carcinoma

   
   
6. 
   

   Inflammatory infiltrate may or may not be present

Special studies

The squamoid form is positive for squamous markers p40, p63, and CK5/6. Often positive for PAX8 (75%) (Fig. 9.1.5). Almost always negative for TTF-1 and thyroglobulin

Positive for squamous markers p40, p63, and CK5/6. Negative for PAX8, TTF-1, and thyroglobulin

Treatment

Complete surgical resection is often not feasible due to advanced tumor stage. Radiotherapy and/or chemotherapy. Radioactive iodine is ineffective

Multimodality therapy for high-stage tumors

Prognosis

Dismal. Almost all cases are fatal. Median survival < 6 months. Death occurs by either airway obstruction or widespread metastases

Stage dependent. Five-year survival for T4 laryngeal carcinoma is approximately 25%-30%

Anaplastic (Undifferentiated) Thyroid Carcinoma

Poorly Differentiated Thyroid Carcinoma

Age

Typically elderly adults, peak in seventh decade. Rare in patients younger than 50. Female predominance (3-4:1)

Typically adults, peak in sixth decade. Slight female predominance

Location

Thyroid gland, often with extension into surrounding soft tissues

Thyroid gland, sometimes with extension into surrounding soft tissues

Symptoms

Rapidly enlarging neck mass, often with dyspnea, dysphagia, and hoarseness

Slowly enlarging neck mass, occasionally with dyspnea, dysphagia, and hoarseness

Signs

Large, firm, nodular thyroid mass, often with extension into neck. Lymphadenopathy with or without distant metastases is common

Nodular thyroid mass, sometimes with extension into neck and with lymphadenopathy

Etiology

Most anaplastic carcinomas arise from well-differentiated thyroid carcinomas (e.g., follicular and papillary carcinomas)

A subset arises from well-differentiated thyroid carcinomas

Histology

1. 
   

   Highly infiltrative often with vascular invasion and invasion of adjacent structures (Fig. 9.2.1)

   
   
2. 
   

   Three histologic patterns, which can coexist in varying proportions in the same tumor:

   
   
   
   
   • 
     

     Spindle cell, which mimics a sarcoma (Fig. 9.2.2)

     
     
   • 
     

     Giant cell, with wildly pleomorphic, bizarre tumor giant cells (Fig. 9.2.3)

     
     
   • 
     

     Squamoid, which resembles squamous cell carcinoma of other organs

   
   
3. 
   

   Marked nuclear pleomorphism (Figs. 9.2.2, 9.2.3 and 9.2.4)

   
   
4. 
   

   Elevated mitotic rates and extensive tumor necrosis are usually seen

   
   
5. 
   

   Frequently accompanied by an infiltrate of neutrophils (Fig. 9.2.4)

   
   
6. 
   

   Anaplastic carcinoma often arises in association with a differentiated thyroid carcinoma, either papillary carcinoma or follicular carcinoma (Fig. 9.2.5)

1. 
   

   May or may not be partially encapsulated, but invasion is present often including vascular invasion and extension beyond the thyroid (Fig. 9.2.8). Rare examples are noninvasive, which behave in a more indolent manner

   
   
2. 
   

   Highly cellular. Most often demonstrates solid, nested (insular), trabecular, and/or microfollicular growth (Fig. 9.2.9). No spindle cell, giant cell, or squamoid histologic patterns

   
   
3. 
   

   Nuclear pleomorphism may be minimal. Instead, the nuclei are often paradoxically uniform and monotonous (Fig. 9.2.10)

   
   
4. 
   

   The mitotic rate is elevated (≥3 mitotic figures/10 high-power fields), and necrosis is frequently present (Figs. 9.2.10 and 9.2.11)

   
   
5. 
   

   No neutrophilic infiltrate

   
   
6. 
   

   A well-differentiated (papillary or follicular) tumor component may be seen

Special studies

Usually diffusely positive for p53 (Fig. 9.2.6). Variably positive for cytokeratins (50%-90%) and PAX8 (75%) (Fig. 9.2.7). Almost always negative for TTF-1 and thyroglobulin

P53 staining is generally absent or patchy. Consistently positive for cytokeratins, TTF-1, thyroglobulin, and PAX8 (Fig. 9.2.12)

Treatment

Complete surgical resection is often not feasible due to advanced tumor stage. Radiotherapy and/or chemotherapy. Radioactive iodine is ineffective

Complete surgical resection with postoperative radioactive iodine. External beam radiation may be added in unresectable or locally advanced tumors

Prognosis

Dismal. Almost all cases are fatal. Median survival < 6 months. Death occurs by either airway obstruction or widespread metastases

Lies between that of well-differentiated and anaplastic carcinoma, with 5-year survival of 50%-70%

Benign Thyroid Follicles in Lymph Node

Metastatic Papillary Thyroid Carcinoma in Lymph Node

Age

Discovered incidentally in adults, fifth through seventh decades

Wide age range; peak in fourth to fifth decades; female predominance

Location

Usually central and occasionally lateral cervical lymph nodes

Most often central neck lymph nodes (level VI), less often lateral lymph nodes (levels II-IV)

Symptoms

Asymptomatic

May be asymptomatic and discovered incidentally, or present in association with painless neck mass

Signs

None

May be discovered incidentally, or in the setting of a neck mass and/or lymphadenopathy

Etiology

Somewhat controversial. May represent epithelial inclusions similar to nodal endosalpingiosis or melanocytic nevi. Some authors believe, however, that all thyroid tissue in lymph nodes represents metastatic disease

Metastasis from papillary carcinoma of the thyroid

Histology

1. 
   

   Strict criteria must be met:

   
   
   
   
   • 
     

     Only one lymph node affected

     
     
   • 
     

     Follicles involve less than one-third of the lymph node (Fig. 9.3.1)

     
     
   • 
     

     Confined to the capsular or subcapsular region of the lymph node (Fig. 9.3.1)

     
     
   • 
     

     Completely bland, without any architectural (e.g., papillary formations) and/or cytologic features (e.g., nuclear enlargement, crowding, chromatin clearing, nuclear contour irregularities including grooves and pseudoinclusions) of papillary carcinoma (Fig. 9.3.2)

     
     
   • 
     

     No psammoma bodies

1. 
   

   Metastases may be very small and discovered incidentally

   
   
2. 
   

   For incidental lesions not associated with a known papillary thyroid carcinoma, should meet at least one criterion:

   
   
   
   
   • 
     

     Involvement of multiple lymph nodes

     
     
   • 
     

     Involvement of more than one-third of any lymph node

     
     
   • 
     

     Involvement of the lymph node parenchyma (i.e., not merely the capsule or subcapsular sinus) (Fig. 9.3.3)

     
     
   • 
     

     Demonstrates architectural (e.g., papillary formations) and/or cytologic features (e.g., nuclear enlargement, crowding, chromatin clearing, nuclear contour irregularities including grooves and pseudoinclusions) of papillary carcinoma (Fig. 9.3.4)

     
     
   • 
     

     Psammoma bodies

Special studies

None useful in this differential diagnosis

None useful in this differential diagnosis

Treatment

Physical examination and ultrasound of thyroid gland and any remaining cervical lymph nodes may be considered

Thyroid lobectomy or thyroidectomy, possibly with lymph node dissection and radioactive iodine, depending on clinical and radiologic findings

Prognosis

Excellent

Excellent

Carcinoma with Thymic-Like Elements (CASTLE)

Anaplastic (Undifferentiated) Thyroid Carcinoma

Age

Adults (mean, 48.5 years); female predominance

Typically elderly adults, peak in seventh decade. Rare in patients younger than 50. Female predominance (3-4:1)

Location

Thyroid gland (usually lower lobes), often with extension into surrounding soft tissues

Thyroid gland, often with extension into surrounding soft tissues

Symptoms

Neck mass, rarely with symptoms of tracheal invasion (hoarseness, dyspnea)

Rapidly enlarging neck mass, often with dyspnea, dysphagia, and hoarseness

Signs

Firm thyroid mass, sometimes with extension into neck. Approximately one-third have lymph node metastases at presentation. Patients are euthyroid

Large, firm, nodular thyroid mass, often with extension into neck and with lymphadenopathy and/or distant metastases

Etiology

May arise from ectopic thymic remnants within the thyroid gland, or possibly from solid cell nests

Most anaplastic carcinomas arise from well-differentiated thyroid carcinomas (e.g., follicular and papillary carcinomas)

Histology

1. 
   

   Highly infiltrative, unencapsulated tumor with frequent extrathyroidal extension (Fig. 9.4.1)

   
   
2. 
   

   Lobulated growth pattern, with lobules separated by bands of dense fibrosis (Fig. 9.4.2)

   
   
3. 
   

   Squamoid histologic features, though usually no keratin pearls. Spindling or streaming can be seen, but no giant cell component (Fig. 9.4.3)

   
   
4. 
   

   May have a lymphoepithelial-like appearance, with syncytial cytoplasm, vesicular nuclei, prominent nucleoli, and tumor-infiltrating lymphocytes (Fig. 9.4.4)

   
   
5. 
   

   Mild to moderate nuclear pleomorphism (Figs. 9.4.3 and 9.4.4)

   
   
6. 
   

   Necrosis can be seen, but the mitotic rates are only mildly elevated

   
   
7. 
   

   Frequently accompanied by a lymphocytic infiltrate, but not neutrophils (Fig. 9.4.5)

   
   
8. 
   

   No component of well-differentiated thyroid carcinoma

1. 
   

   Highly infiltrative often with vascular invasion and invasion of adjacent structures

   
   
2. 
   

   No lobular growth pattern

   
   
3. 
   

   Three histologic patterns, which can coexist in varying proportions in the same tumor: squamoid, spindle cell, and giant cell

   
   
4. 
   

   No lymphoepithelial appearance

   
   
5. 
   

   Often marked nuclear pleomorphism (Fig. 9.4.7)

   
   
6. 
   

   Elevated mitotic rates and extensive tumor necrosis are usually seen

   
   
7. 
   

   Frequently accompanied by an infiltrate of inflammatory cells, especially neutrophils (Fig. 9.4.8)

   
   
8. 
   

   Anaplastic carcinoma often arises in association with a differentiated thyroid carcinoma, either papillary carcinoma or follicular carcinoma (Fig. 9.4.9)

Special studies

Identical to thymic carcinoma: positive for squamous markers p40, p63, and CK5/6. Variably positive for PAX8. Positive for CD5 and c-kit (Fig. 9.4.6). Negative for TTF-1 and thyroglobulin

Squamoid form is positive for squamous markers p40, p63, and CK5/6. Often positive for PAX8 (75%). Almost always negative for TTF-1 and thyroglobulin. Negative for c-kit and CD5

Treatment

Complete surgical resection, usually with postoperative radiotherapy. Radioactive iodine is ineffective

Complete surgical resection, usually with adjuvant radiotherapy and/or chemotherapy. Radioactive iodine is ineffective

Prognosis

Good. Five-year survival around 90%

Dismal. Almost all cases are fatal. Median survival < 6 months. Death occurs by either airway obstruction or widespread metastases

Columnar Variant of Papillary Thyroid Carcinoma

Cribriform Morular Variant of Papillary Thyroid Carcinoma

Age

Adults, wide age range

Typically young women

Location

Thyroid gland

Thyroid gland

Symptoms

Thyroid nodule

Thyroid nodule

Signs

Solitary or multiple thyroid nodules, often with evidence of regional or distant metastatic disease

Solitary or multiple thyroid nodules, usually without evidence of regional or distant metastatic disease

Etiology

Unknown

A subset arises in patients with familial adenomatous polyposis (germline APC mutation)

Histology

1. 
   

   Papillary, often with complex villous structures and cellular necrosis. Very reminiscent of colorectal carcinoma. Cribriforming growth is not typically seen (Fig. 9.5.1)

   
   
2. 
   

   Colloid usually present, at least focally

   
   
3. 
   

   No squamoid morules

   
   
4. 
   

   Characteristic nuclear atypia of conventional papillary carcinoma usually not well developed

   
   
5. 
   

   Psammoma bodies are rare

   
   
6. 
   

   Hyperchromatic nuclei with stratification, reminiscent of colonic adenomas/carcinomas (Fig. 9.5.2). Subnuclear vacuoles may be seen

   
   
7. 
   

   Usually aggressive histologic features including vascular invasion, elevated mitotic rate, and necrosis (often “dirty” necrosis, similar to colonic adenocarcinoma) (Fig. 9.5.1)

1. 
   

   Complex architectural patterns that often include papillary, cribriform, solid, and trabecular growth. The cribriform pattern is seen as anastomosing bars and arches of cells in the absence of intervening fibrovascular stroma (Fig. 9.5.4)

   
   
2. 
   

   Colloid is typically scant or absent (Fig. 9.5.4)

   
   
3. 
   

   May demonstrate nests of cells exhibiting squamoid metaplasia and intranulcear inclusions known as morules (Fig. 9.5.5)

   
   
4. 
   

   Tumor cells are often tall with nuclear stratification and abundant eosinophilic cytoplasm. Characteristic nuclear atypia of conventional papillary carcinoma usually not well developed (Fig. 9.5.5)

   
   
5. 
   

   Psammoma bodies are rare

   
   
6. 
   

   No subnuclear vacuoles

   
   
7. 
   

   Usually no aggressive features (e.g., vascular invasion, elevated mitotic rate, necrosis)

Special studies

Negative staining for nuclear beta-catenin. Staining for ER and PR is variable. A subset is positive for CDX2 (Fig. 9.5.3)

Positive for ER and PR (Fig. 9.5.6). Beta-catenin staining in a nuclear distribution (Fig. 9.5.7). CDX2 may be focally positive in the squamoid morules (Fig. 9.5.8)

Treatment

Thyroidectomy, radioactive iodine. External beam radiation may be indicated in locally aggressive cases

Thyroidectomy, with or without radioactive iodine

Prognosis

Appears to be more aggressive than conventional papillary carcinoma, with higher rates of extrathyroidal extension, metastatic disease, and death. Well-encapsulated examples may be more indolent

Similar to conventional papillary carcinoma

Columnar Variant of Papillary Thyroid Carcinoma

Tall Cell variant of Papillary Thyroid Carcinoma

Age

Adults, wide age range

Adults, peak in sixth decade

Location

Thyroid gland

Thyroid gland

Symptoms

Neck mass

Neck mass

Signs

Solitary or multiple thyroid nodules, often with evidence of regional or distant metastatic disease

Solitary or multiple thyroid nodules, often with evidence of regional or distant metastatic disease. Extrathyroidal extension into adjacent structures of the neck is often present

Etiology

Unknown

Unknown

Histology

1. 
   

   Papillary, often with complex villous structures and cellular necrosis. Very reminiscent of colorectal carcinoma (Fig. 9.6.1)

   
   
2. 
   

   Characteristic nuclear atypia of conventional papillary carcinoma usually not well developed. The nuclei are often hyperchromatic (lack chromatin clearing), and nuclear pseudoinclusions are not common

   
   
3. 
   

   Tumor cells are tall. Nuclei are hyperchromatic, elongated, and stratified, reminiscent of colonic adenomas/carcinomas (Fig. 9.6.2). Subnuclear vacuoles may be seen (Fig. 9.6.3)

   
   
4. 
   

   Usually aggressive histologic features including vascular invasion, elevated mitotic rate, and/or necrosis (often “dirty” necrosis, similar to colonic adenocarcinoma)

1. 
   

   Papillary, follicular, and solid growth patterns

   
   
2. 
   

   Papillae often arranged in long parallel arrays (Fig. 9.6.5)

   
   
3. 
   

   Nuclear atypia of papillary carcinoma is highly developed including numerous nuclear grooves and pseudoinclusions (Fig. 9.6.6)

   
   
4. 
   

   The nuclei tend to be uniformly aligned, lacking prominent overlapping and stratification (Figs. 9.6.5 and 9.6.6)

   
   
5. 
   

   The tumor cells are tall (height of the cells is at least two to three times greater than the width of the cells). The cytoplasm is abundant and eosinophilic (Figs. 9.6.5 and 9.6.6)

   
   
6. 
   

   Often associated with highly infiltrative growth and extrathyroidal extension. Tumor necrosis is not common

Special studies

A subset are positive for CDX2 (Fig. 9.6.4) Positive for TTF-1, PAX8, and thyroglobulin

Negative for CDX2 Positive for TTF-1, PAX8, and thyroglobulin

Treatment

Thyroidectomy, radioactive iodine. External beam radiation may be indicated in locally aggressive cases

Thyroidectomy, radioactive iodine. External beam radiation may be indicated in locally aggressive cases

Prognosis

Appears to be more aggressive than conventional papillary carcinoma, with higher rates of extrathyroidal extension, metastatic disease, and death. Well-encapsulated examples may be more indolent

More aggressive than conventional papillary carcinoma, with higher rates of extrathyroidal extension, metastatic disease, and death

Follicular Adenoma

Encapsulated Follicular Variant of Papillary Carcinoma

Age

Wide age range, most often middle-aged women

Wide age range, most often middle-aged women

Location

Thyroid gland

Thyroid gland

Symptoms

Painless neck mass or asymptomatic. Patients usually euthyroid (except in hyperfunctional adenomas, where patients become hyperthyroid)

Painless neck mass or asymptomatic. Patients usually euthyroid

Signs

Variably sized thyroid nodule, usually solitary

Variably sized thyroid nodule, often solitary

Etiology

Unknown. Not associated with iodine deficiency

Some are associated with prior radiation to neck. Not associated with iodine deficiency

Histology

1. 
   

   Well-circumscribed nodule usually surrounded by a fibrous capsule of variable thickness (Fig. 9.7.1)

   
   
2. 
   

   No invasive growth

   
   
3. 
   

   Architecturally variable, ranging from normofollicular to microfollicular to trabecular to solid (Fig. 9.7.2)

   
   
4. 
   

   The tumor cells are uniformly spaced around the follicular spaces

   
   
5. 
   

   The nuclei are small, normochromatic, and round to oval with smooth contours (Fig. 9.7.3)

   
   
6. 
   

   Colloid is amphophilic or eosinophilic

1. 
   

   Well-circumscribed nodule surrounded by a fibrous capsule of variable thickness (Fig. 9.7.4). For those tumors that lack a well formed capsule, the periphery of the nodule is highly circumscribed

   
   
2. 
   

   Invasion of the tumor capsule and intracapsular blood vessels may or may not be present. The noninvasive form is now classified as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP)

   
   
3. 
   

   Typically hypercellular with variable architecture ranging from normofollicular to microfollicular to trabecular to solid. A macrofollicular pattern can occur but is rare. Well-developed papillary structures are few in number or entirely absent (Fig. 9.7.5)

   
   
4. 
   

   Colloid is often brightly eosinophilic and scalloped at the periphery of the follicles (so-called bubblegum colloid) (Figs. 9.7.5 and 9.7.6)

   
   
5. 
   

   Nuclear atypia including nuclear elongation, chromatin clearing, crowding with overlap, nuclear membrane irregularities, and nuclear grooves. Nuclear pseudoinclusions are rare (Figs. 9.7.6 and 9.7.7)

Special studies

Although many immunohistochemical markers have been proposed for this differential diagnosis (e.g., galectin-3, HBME1, CK19), none are entirely sensitive or specific for this differential diagnosis. Interpretation of the immunohistochemical findings must be guided by the morphologic findings

Although many immunohistochemical markers have been proposed for this differential diagnosis (e.g., galectin-3, HBME1, CK19), none are entirely sensitive or specific for this differential diagnosis. Interpretation of the immunohistochemical findings must be guided by the morphologic findings

Treatment

Lobectomy

Lobectomy alone is adequate for noninvasive form (NIFTP). For invasive tumors, thyroidectomy with postoperative radioactive iodine is standard therapy for larger tumors

Prognosis

Excellent

Noninvasive type (NIFTP) behaves in an essentially benign fashion. For invasive types, prognosis is very good overall but likely depends on number of invasive foci, similar to follicular carcinoma. Do not typically metastasize to lymph nodes, but rather to distant sites like lung and bone, also similar to follicular carcinoma

Encapsulated Follicular Carcinoma

Follicular Adenoma with Worrisome Histologic Alterations Following Fine Needle Aspiration of the Thyroid (WHAFFT)

Age

Wide age range, peak in fifth to sixth decades

Wide age range, most often middle-aged women

Location

Thyroid gland

Thyroid gland

Symptoms

Painless neck mass, or asymptomatic. Patients usually euthyroid

Painless neck mass, or asymptomatic. Patients usually euthyroid (except in hyperfunctional adenomas, where patients become hyperthyroid)

Signs

Variably sized thyroid nodule, often solitary

Variably sized thyroid nodule, usually solitary

Etiology

Largely unknown. Some association with iodine deficiency. Some association with radiation to neck, though not as strong as papillary carcinoma

Injury and reparative changes as a result of a prior fine needle aspiration of the thyroid nodule

Histology

1. 
   

   Well-circumscribed nodule surrounded by a capsule that is often thick and irregular

   
   
2. 
   

   As the carcinoma invades the tumor capsule, it gains access to intracapsular blood vessels and grows horizontally within these intracapsular vessels. This pattern of spread often gives rise to a “mushrooming” or “fish-hooking” appearance (Figs. 9.8.1 and 9.8.2)

   
   
3. 
   

   Vascular invasion is characterized by adherence of tumor follicles to the vessel wall (not free floating) with protrusion of tumor follicles into the lumen. The tumor follicles are lined by endothelial cells (Fig. 9.8.3)

   
   
4. 
   

   In unequivocal capsular invasion, the tumor shows contiguous, full-thickness extension through the capsule (Fig. 9.8.4). The invasive foci are more expanded and rounded than the linear tracts related to fine needle aspiration

   
   
5. 
   

   Usually multiple foci of invasive growth are encountered

   
   
6. 
   

   No evidence of needle track changes in the area of invasion

1. 
   

   Well-circumscribed nodule surrounded by a capsule of varying thickness

   
   
2. 
   

   WHAFFT include ischemic necrosis, linear disruption of the tumor capsule, and mechanical displacement of tumor follicles (Fig. 9.8.5)

   
   
3. 
   

   The area of capsular disruption tends to be a straight linear tract. Displacement of tumor follicles into the area of capsular disruption mimics capsular invasion (Fig. 9.8.6)

   
   
4. 
   

   Tumor follicles may also be mechanically displaced into intracapsular blood vessels. Unlike true vascular invasion, these displaced follicles are free floating without adhesion to the vessel wall, and are associated with secondary reactive changes (Figs. 9.8.7 and 9.8.8)

   
   
5. 
   

   Secondary reactive changes including hemorrhage, hemosiderin, scarring, and granulation tissue

   
   
6. 
   

   No vascular invasion

   
   
7. 
   

   Usually only one or two foci of pseudoinvasion

Special studies

Not helpful in this differential diagnosis

Not helpful in this differential diagnosis

Treatment

For small tumors with only a few foci of invasion, lobectomy may be considered. For larger or more invasive tumors, thyroidectomy and postoperative radioactive iodine

Lobectomy

Prognosis

Depends on extent of invasion Tumors with capsular invasion only behave in an essentially benign manner.

Tumors with fewer than four foci of vascular invasion have a 5% risk of distant metastasis. Tumors with more than three foci of vascular invasion have a worse prognosis, especially the Hurthle cell variant, which has up to a 47% recurrence rate.

Tends to metastasize not to lymph nodes, but rather to distant sites like lung and bone

Excellent

Encapsulated Follicular Carcinoma

Encapsulated Follicular Variant of Papillary Carcinoma with Invasion

Age

Wide age range, peak in fifth to sixth decades

Wide age range, most often middle-aged women

Location

Thyroid gland

Thyroid gland

Symptoms

Painless neck mass, or asymptomatic. Patients usually euthyroid

Painless neck mass, or asymptomatic. Patients usually euthyroid

Signs

Variably sized thyroid nodule, often solitary

Variably sized thyroid nodule, often solitary

Etiology

Largely unknown. Some association with iodine deficiency. Some association with radiation to neck, though not as strongly as papillary carcinoma

Some are associated with prior radiation to neck. Not associated with iodine deficiency

Histology

1. 
   

   Well-circumscribed nodule surrounded by a capsule that is often very thick (Fig. 9.9.1)

   
   
2. 
   

   As the carcinoma invades the tumor capsule, it gains access to intracapsular blood vessels and grows horizontally within these intracapsular vessels. This pattern of spread often gives rise to a “mushrooming” or “fish-hooking” appearance (Fig. 9.9.1)

   
   
3. 
   

   Vascular invasion is characterized by adherence of tumor follicles to the vessel wall (not free floating) with protrusion of tumor follicles into the lumen. The tumor follicles are lined by endothelial cells (Fig. 9.9.2)

   
   
4. 
   

   Typically hypercellular with microfollicular, trabecular, or solid growth patterns

   
   
5. 
   

   The follicles cells show atypical features including nuclear enlargement and nuclear hyperchromasia and mitotic figures, but the nuclear atypia of papillary carcinoma are not developed (Fig. 9.9.3)

   
   
6. 
   

   A variant form, Hurthle cell (oncocytic) carcinoma, has abundant granular, eosinophilic cytoplasm, and prominent nucleoli

1. 
   

   Well-circumscribed nodule surrounded by a fibrous capsule of variable thickness (Fig. 9.9.4)

   
   
2. 
   

   Invasion of the tumor capsule and intracapsular blood vessels is present (Fig. 9.9.4)

   
   
3. 
   

   Typically hypercellular with variable architecture ranging from normofollicular to microfollicular to trabecular to solid. Well-developed papillary structures are few in number or entirely absent (Fig. 9.9.5)

   
   
4. 
   

   Nuclear atypia including nuclear elongation, chromatin clearing, crowding with overlap, nuclear membrane irregularities, and nuclear grooves. Nuclear pseudoinclusions are rare (Fig. 9.9.5)

   
   
5. 
   

   Colloid is often brightly eosinophilic and scalloped at the periphery of the follicles (so-called bubblegum colloid) (Fig. 9.9.5)

Special studies

None are useful in this differential diagnosis

None are useful in this differential diagnosis

Treatment

For small tumors with only a few foci of invasion, lobectomy may be considered For larger or more invasive tumors, thyroidectomy and postoperative radioactive iodine

For small tumors with only a few foci of invasion, lobectomy may be considered For larger or more invasive tumors, thyroidectomy and postoperative radioactive iodine

Prognosis

Depends of extent of invasion

Tumors with capsular invasion only behave in an essentially benign manner

Tumors with fewer than four foci of vascular invasion have a 5% risk of distant metastasis

Tumors with more than three foci of vascular invasion have a worse prognosis, especially the Hurthle cell variant, which has a recurrence rate of up to 47%

Tends to metastasize not to lymph nodes, but rather to distant sites like lung and bone

Prognosis is very good overall but likely depends on number of invasive foci, similar to follicular carcinoma. Do not typically metastasize to lymph nodes, but rather to distant sites like lung and bone, also similar to follicular carcinoma