Classification of Thyroid Tumors

The conventional classification based on morphology and clinical features is largely supported by molecular data currently available. Genetic profiles of four main categories appear distinctly different from each other with a few areas of overlap.

The classification of thyroid tumors modified from WHO classification (2004) is as follows:

Tumors of Follicular Epithelium:
■„Follicular adenoma (including Hurthle cell adenoma)
■„Hyalinizing trabecular adenoma ■„Follicular carcinoma (including Hurthle cell carcinoma)
– Minimally invasive – – Widely invasive
■„Papillary carcinomas
■„Poorly differentiated carcinoma ■„Anaplastic carcinoma
■„Squamous cell carcinoma ■„Mucoepidermoid carcinoma ■„Sclerosing mucoepidermoid carcinoma with eosinophilia ■„Mucinous carcinoma

Tumors with C Cell Differentiation
Medullary carcinoma

Tumors with Mixed Differentiation
■„Collision tumor—follicular/papillary or follicular/medullary
■„Mixed differentiated carcinoma intermediate type

Tumors Showing Thymic or Related Branchial Pouch Differentiation
■„Ectopic thymoma
■„Spindle epithelial tumor with thymus-like
element (SETTLE)
■„Carcinoma showing thymus-like element (CASTLE).

Tumors of Lymphoid Cells
■„Malignant lymphoma ■„Plasmacytoma

Mesenchymal Tumors
■„Smooth muscle tumors ■„Peripheral nerve sheath tumors ■„Paragangliomas
■„Solitary fibrous tumors ■„Follicular dendritic cell tumors ■„LCH



Thyroid Tumors

Thyroid tumors account to 1% of all malignancies in developed countries and 0.2% of cancer deaths. They are the most common malignancies of the endocrine system and pose a significant challenge to pathologists, surgeons, and oncologists. Most of the carcinomas affect young and middle-aged adults and are indolent malignancies with a 10-year survival that exceeds 90%. There has been an increase in the incidence rate of these tumors worldwide which can be largely attributed to more sophisticated diagnostic methods and a change in diagnostic practices with an increasing number of smaller tumors being detected of late. Thyroid tumor pathology is an area replete with diagnostic challenges. Though there are typical morphological patterns described, overlaps with non-neoplastic entities pose diagnostic difficulties. Updates in this field include ancillary and research aiming at techniques that can further narrow down our diagnosis from the different “indeterminate/gray zone” lesions detected on screening.

Axillary Management in Patients with Isolated Tumor Cells (ITCs) and Micrometastatic Disease

  • It is clear that patients with pathologically negative sentinel lymph nodes:
    • Do not require completion ALND:
      • But the management of patients with ITCs and micrometastatic disease in sentinel lymph nodes:
        • Has extensively been debated
  • Micrometastatic disease is defined as:
    • Tumor deposits spanning:
      • 0.2 mm to 2.0 mm:
        • Within lymph nodes
  • ITCs are:
    • Groupings of cells not greater than 0.2 mm or 200 cells:
      • In a single lymph node cross section
  • According to the American Joint Committee on Cancer (AJCC) staging guidelines:
    • Patients with ITCs are N0(i+)
    • Patients with micrometastases in one to three axillary lymph nodes are N1mi
  • ACOSOG Z0010:
    • Is one of the largest trials to prospectively evaluate the significance of small metastases in sentinel nodes
    • Hematoxylin and eosin (H&E) tumor-free sentinel nodes:
      • From patients with early breast cancer were evaluated in a central laboratory with:
        • Immunohistochemistry (IHC)
    • Micrometastatic or ITC disease:
      • Was found in 11% of 3,326 sentinel lymph nodes
    • With a median follow-up of 6.3 years:
      • Occult sentinel lymph node metastases:
        • Were not associated with differences in overall survival, disease-free survival, or recurrence:
          • When compared with patients with IHC-negative lymph nodes
  • A subset analysis of NSABP-32:
    • Looked retrospectively at patients with occult metastatic disease:
      • Including patients with micrometastatic or isolated tumor cells
    • In patients who were sentinel node negative:
      • 16% had occult metastases detected on further evaluation:
        • 11% of occult metastases were isolated tumor-cell clusters, 4% were micrometastases, and less than 1% of patients had macrometastatic deposits seen on additional sectioning of the lymph node
    • Log-rank tests indicated that patients with occult metastasis:
      • Had worse overall survival (95% versus 96%), disease-free survival (87% versus 89%), and distant disease-free interval (90% versus 93%):
        • When compared with patients without occult metastases
      • Although statistically significant:
        • These differences were not felt to be clinically relevant
    • There was no improvement in overall or disease-free survival:
      • When patients with occult metastasis underwent completion ALND

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Management of Patients with Tumor-Free Sentinel Lymph Nodes in Breast Cancer

  • Randomized clinical trials support the use of SLNB without ALND:
    • For node-negative patients
  • These studies demonstrated very low axillary recurrence rates:
    • In patients with negative sentinel lymph nodes:
      • Regardless of receptor status
      • Type of breast operation
      • Patient age
  • The ASCO guidelines state:
    • That women with early-stage breast cancer without sentinel nodal metastases:
      • Should not undergo ALND
  • The first use of SLNB without ALND was a prospective observational study in 1994:
    • Which evaluated 125 patients with SLNB alone
  • NSABP B-32:
    • A phase III trial involving 80 centers in Canada and the United States
    • Prospectively randomized 3,989 sentinel lymph node–negative patients to SLNB plus ALND or SLNB alone
    • Patients were stratified based on age, tumor size, and surgical approach
    • Regional recurrence was rare in both patients who underwent SLNB alone and those who had a completion ALND and was not statistically significantly different
    • Of the 22 regional events in both groups:
      • 10 breast cancer recurrences were in the axilla:
        • For a rate of less than 1%
      • Two of these recurrences occurred in patients who were treated with ALND and eight in patients who underwent SLNB alone
      • There was no difference in overall or disease-free survival between groups:
        • And there were fewer complications in the SLNB-alone group
    • The results of NSABP B-32:
      • Have also been seen in other studies
  • Guided by this strong evidence:
    • SLNB alone has replaced ALND for sentinel node–negative patients

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Normocalcemic Primary Hyperparathyroidism: Further Characterization of a New Clinical Phenotype


Context: Patients with elevated parathyroid hormone (PTH) and consistently normal serum calcium levels, in whom secondary causes of hyperparathyroidism have been excluded, may represent the earliest presentation of primary hyperparathyroidism (PHPT).

Objective: The objective of the study was to characterize patients with normocalcemic PHPT referred to a bone disease unit.

Design: This was a longitudinal cohort study.

Setting: Ambulatory patients were referred to the metabolic bone disease unit.

Patients: The study population included 37 patients [aged 58 yr, range 32–78; 95% female; serum calcium, 9.4 ± 0.1 (SEM) mg/dl (2.3 ± 0.02 mmol/liter), reference range, 8.5–10.4 (2.1–2.6 mmol/liter); PTH, 93 ± 5 pg/ml].

Interventions: Interventions included yearly (median 3 yr; range 1–8 yr) physical examination, biochemical indices, and bone mineral density (BMD).

Main Outcome Measures: We measured the development of features of PHPT.

Results: Evaluation for classical features of PHPT revealed a history of kidney stones in five (14%), fragility fractures in four (11%), and osteoporosis in 57% [spine (34%), hip (38%), and/or distal one third radius (28%)]. BMD did not show preferential bone loss at the distal one third radius (T scores: spine, −2.00 ± 0.25; hip, −1.84 ± 0.18; one third radius, −1.74 ± 0.22). Further signs of PHPT developed in 40% (seven hypercalcemia; one kidney stone; one fracture; two marked hypercalciuria; six had >10% BMD loss at one or more site(s) including four patients developing World Health Organization criteria for osteoporosis). Seven patients (three hypercalcemic, four persistently normocalcemic) underwent successful parathyroidectomy.

Conclusions: Patients seen in a referral center with normocalcemic hyperparathyroidism have more substantial skeletal involvement than is typical in PHPT and develop more features and complications over time. These patients may represent the earliest form of symptomatic, rather than asymptomatic, PHPT.

Lowe, Hyesoo et al. “Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype.” The Journal of clinical endocrinology and metabolism 92 8 (2007): 3001-5 .

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Kidney Stones- July Parathyroid Awareness Month

  • In patients with PHPT and calcium oxalate kidney stones:
    • Surgery for primary hyperparathyroidism (PHPT):
      • Can reduce stone formation by up to 90%

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Predictors of Multigland Disease in Hyperparathyroidism

  • No study has yet identified a reliable predictor:
    • For determining which patients with sporadic hyperparathyroidism:
      • Will have multigland disease:
        • The exception is in familial, secondary, and tertiary hyperparathyroidism:
          • Because of the nearly uniform incidence of four-gland hyperplasia:
            • All these patients are managed with bilateral neck exploration:
              • And either total parathyroidectomy with autotransplantation or three-and-a-half gland parathyroidectomy
  • Although some surgeons believe that patients with higher preoperative PTH or calcium levels (or both):
    • Are more likely to have multi-gland disease:
      • This has not been proved to be true in clinical studies

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  • What are the three types of wound healing?
    • Primary closure / intention
    • Secondary intention
    • Tertiary intention:
      • Delayed Primary Closure: DPC
  • What is primary intention?
    • When the edges of a clean wound are closed in some manner immediately:
      • For example:
        • Suture
        • Steri-Strips®
        • Staples
  • What is secondary intention?
    • When a wound is allowed to remain open:
      • And heal by granulation, epithelization, and contraction:
        • Used for dirty wounds:
          • Otherwise an abscess can form
  • What is tertiary intention?
    • When a wound is allowed to remain open for a time and then closed:
      • Allowing for débridement and other wound care to reduce bacterial counts prior to closure:
        • Delayed primary closure (DPC)

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Suture Techniques

  • What is a taper-point needle?
    • Round body:
      • Leaves a round hole in tissue:
        • Spreads without cutting tissue
    • What is it used for?
      • Suturing of soft tissues other than skin:
        • For example:
          • GI tract, muscle, nerve, peritoneum, fascia
  • What is a conventional cutting needle?
    • Triangular body with the sharp edge toward the inner circumference:
      • Leaves a triangular hole in tissue
    • What are its uses?
      • Suturing of skin
  • What is a simple interrupted stitch?
  • What is a vertical mattress stitch?
    • Simple stitch is made;
      • The needle is reversed, and a small bite is taken from each wound edge:
        • The knot ends up on one side of the wound
  • What is the vertical mattress stitch also known as?
    • Far–far, near–near stitch:
      • Oriented perpendicular to wound
  • What is it used for?
    • Difficult-to-approximate skin edges:
      • Everts tissue well
  • What is a simple running (continuous) stitch?
    • Stitches made in succession without knotting each stitch
  • What is a subcuticular stitch?
    • Stitch (usually running) placed just underneath the epidermis:
      • Can be either absorbable or non-absorbable:
        • Pull-out stitch if non-absorbable
  • What is a purse-string suture?
    • Stitch that encircles a tube perforating a hollow viscus:
      • For example:
        • Jejunostomy tube
        • Gastrostomy tube:
          • Allowing the hole to be drawn tight and thus preventing leakage
  • What are metallic skin staples?
  • What is a staple removal device?
  • What is a gastrointestinal anastomosis (GIA) device?
    • Stapling device that lays two rows of small staples in a hemostatic row:
      • And automatically cuts in between them
  • What is a Lembert stitch?
    • It is a second layer in bowel anastomoses
    • Technique:
      • The needle is inserted perpendicular to the epidermis, approximately 8 mm distant to the wound edge.
      • With a fluid motion of the wrist, the needle is rotated superficially through the dermis, and the needle tip exits the skin 2 mm distant from the wound edge on the ipsilateral side.
      • The needle body is grasped with surgical forceps in the left hand and reloaded onto the needle driver.
      • The needle is then inserted perpendicular to the skin on the contralateral side of the wound edge, 2 mm distant from the wound edge.
      • The needle is again rotated superficially through its arc, exiting 8 mm from the incised wound edge.
      • The suture material is then tied off gently, with care being taken to minimize tension across the epidermis and avoid overly constricting the wound edges
  • What is a Connell’s stitch?
    • The first mucosa-to-mucosa layer in an anastomosis:
      • Basically, a running U stitch
    • The Cushing and Connell suture technique:
      • Is often used to close the incisions in hollow organs such as the stomach, urinary bladder, and uterus
    • In the Cushing suture technique:
      • The suture penetrates into the submucosa without penetrating the organ lumen
      • The suture runs from both sides of the incision:
        • Parallel to each other
    • The Connell suture technique is almost identical to the Cushing suture technique:
      • These two suture techniques are separated according to the tissue they penetrate during suture passage
      • While the Cushing suture technique is also passed through the submucosa, Connell suture technique is used to pass through the lumen
    • While applying these techniques, the following steps are followed:
      • A directionally opposed suture passage is made parallel to the incision.
      • Suture passage is made from the other side of the incision in the same direction as the incision, parallel to the first passage
      • The beginning of the suture line is fixed with a knot.
      • Starting from the back of the knot, a suture passage is made in the direction of the incision
      • A passage is made from the other side of the incision parallel to the first pass and in the same direction
      • When the suture is pulled, the tissue becomes inverted and the knot is buried under the skin
      • A suture passage is made in the direction of the incision
      • A passage is made from the other side of the incision parallel to the first pass and in the same direction
      • The last two steps are repeated throughout the incision
      • After the incision line is crossed, End of suture line is fixed by repeating first three steps
  • What is a suture ligature (a.k.a. “stick tie”)?
    • Suture is anchored by passing it through the vessel on a needle before wrapping it around and occluding the vessel:
      • Prevents slippage of knot-use on larger vessels

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Sutures and Stitches

  • General Information:
    • What is a suture?
      • Any strand of material used to ligate blood vessels or to approximate tissues
    • How are sutures sized?
      • By diameter;:
        • Stated as a number of 0’s:
          • The higher the number of 0’s, the smaller the diameter:
            • For example a 2-0 suture has larger diameter than 5-0 suture
    • Which is thicker, 1-0 suture or 3-0 suture?
      • 1-0 suture
  • Classification:
    • What are the two most basic suture types?
      • Absorbable and non-absorbable
    • What is an absorbable suture?
      • Suture that is completely broken down by the body:
        • Dissolving suture
    • What is a nonabsorbable suture?
      • Suture is not broken down:
        • Permanent suture
  • Sutures:
    • Catgut:
      • What are “catgut” sutures made of?
        • Purified collagen fibers from the intestines of healthy cows or sheep
      • What are the two types of gut sutures?
        • Plain and chromic
      • What is the difference between plain and chromic gut?
        • Chromic gut is treated with chromium salts (chromium trioxide):
          • Which results in more collagen cross-links:
            • Making the suture more resistant to breakdown by the body
  • Vicryl® Suture
    • What is it?
      • Absorbable, braided, and multi-filamentous copolymer of lactide and glycoside
    • How long does it retain its strength?
      • 60% at 2 weeks
      • 8% at 4 weeks
    • Should you ever use PURPLE-colored Vicryl® for skin closure?
      • No:
        • It may cause purple tattooing
  • PDS®
    • What is it?
      • Absorbable, monofilament polymer of polydioxanone:
        • Absorbable fishing line
    • How long does it maintain its tensile strength?
      • 70% to 74% at 2 weeks
      • 50% to 58% at 4 weeks
      • 25% to 41% at 6 weeks
    • How long does it take to complete absorption?
      • 180 days (6 months)
  • What is silk?
    • Braided protein filaments:
      • Spun by the silkworm larva:
        • Known as a nonabsorbable suture
  • What is Prolene®?
    • Non-absorbable suture:
      • Used for vascular anastomoses, hernias, abdominal fascial closure
  • What is nylon?
    • Non-absorbable “fishing line”
  • What is monocryl?
    • Absorbable monofilament
  • What kind of suture should be used for the biliary tract or the urinary tract
      • Otherwise the suture will end up as a nidus for stone formation

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