Under one cover: grossing, staging, and reporting

Parathyroidectomy is performed to treat hyperparathyroidism.¹ The surgery may involve resection of a single gland when preoperative investigations have identified a culprit lesion. If the surgeon encounters an unusually large, adjacent gland, there may be a biopsy of a second gland, and, rarely, patients may have double adenomas, resulting in removal of two parathyroids.^2,3 Patients who have multiglandular parathyroid disease, either in the setting of secondary or tertiary hyperparathyroidism or those with genetic predisposition to parathyroid proliferative disorders, usually undergo resections of three glands, with biopsy of the fourth most-normal gland, which is implanted in a surgically accessible location (often the forearm) in the event of recurrent disease.

Central compartment neck dissection and thymectomy may be performed during parathyroidectomy because parathyroid tissue can be found within these tissues.

II. What do we expect to see in a parathyroid resection specimen macroscopically and microscopically?

The findings may include normal, diffusely abnormal, and/or nodular parathyroid tissue. Comprehensive evaluation of the specimen is critical for the assessment of the lesion(s) to establish future possible management plans. The only way to accurately report the actual disease is to have appropriate measurements, weights, and sampling for microscopic assessment.

The size of each component of the specimen is an important feature that must be documented; this includes three dimensions and the weight of the specimen. The orientation of the gland is an important aspect of handling a parathyroid (Figure 6-1); identification of the hilum by the localization of vessels allows proper sectioning, because this is the usual location of nontumorous tissue in glands with neoplasia.

Occasionally, these procedures may also resect portions of adjacent tissues, usually central compartment of the neck, thymus, and thyroid. The reader is referred to the chapter on the thyroid for thyroid specimens.

III. Typical gross photos of parathyroid resection specimens

Gross diagnosis based on macroscopic observation is critical, particularly in noting areas with different appearances and submitting them for microscopic examination. The size, delineation and encapsulation, texture, and color of nodules must be appreciated. Correlation with the microscopic findings will dramatically enhance diagnostic accuracy.

Gross photographs of parathyroid glands are provided in Figures 6-2 through 6-4.

IV. Dissection techniques: step-by-step description

1. How to orient parathyroid resection specimens
   Parathyroid biopsies consist of small fragments that do not require orientation.Parathyroidectomy specimens should be examined to identify the hilum of the gland. This is important to determine the plane of section to ensure identification of nontumorous parathyroid tissue in a gland with a neoplasm. Central compartment and thymectomy specimens should be examined to identify all nodular tissues within the fat of these structures.
2. Resection margin documentation
   Glands removed for infiltrative neoplasms require resection margin evaluation. Ink the outer surface of the specimen; apply acetone/acetic acid to fix the ink, then pat and air dry.
3. Measurements
   Specimens should be measured to provide the size in three dimensions. Although the weight of a biopsy is not required, all parathyroidectomy specimens should be weighed.
4. External examination
   The external surface of the gland may have adhesions.
5. Sectioning
   The parathyroid gland should be sectioned to include the hilum with sections every 2 to 3 mm. This allows identification of the normal gland, which is usually in the hilum, as well as the lesion. Careful examination of the entire lesion is warranted. Any adherent tissue should be documented.
6. Tissue banking
   If tumor is grossly present and a research protocol is available, tissue banking should be considered according to the institutional guidelines. Tissue banking for future studies—such as molecular, flow cytometry, next-generation sequencing (NGS), and other potential research projects—should be considered. Document the “cold ischemia time,” if appropriate (varies by institution) and the type of medium used, if any. Collect fresh tissue or snap-frozen tissue for special studies according to protocol. Formalin-fixed paraffin-embedded tissue that is representative of biobanked tissue assists in confirmation of the material studied and, when required, can be repatriated to diagnostic tissue, as occasionally may be necessary for small lesions.
7. Fixation
   Fix the specimen for several hours; overnight fixation is not usually required for these small specimens. However, if the specimen includes adjacent or adherent thyroid, this may be required (see chapter on thyroid).
8. Submitting sections
   In most cases, the entire specimen should be submitted in serial sections, which allows accurate examination of grossly identified nodules and also permits documentation of nontumorous parenchyma. In the case of a thymectomy and/or central compartment dissection, submission in toto is required to identify any parathyroid tissue.
9. Documentation of sections
   Document the gross description and sections as illustrated in section V, below.

V. Gross descriptions using paragraph system

The paragraph system can be used to describe thyroid resection specimens.

Parathyroid biopsy
The specimen identified with the patient’s name and as “right inferior parathyroid” consists of a small piece of soft tan tissue that measures 0.1 × 0.1 × 0.1 cm. It is frozen for intraoperative consultation.

1A: Frozen tissue resubmitted
Frozen section diagnosis should be documented in the appropriate field, along with documentation of to whom and what time it was reported.

Parathyroidectomy specimen
The specimen identified with the patient’s name and as “right inferior parathyroid” consists of a piece of soft tan tissue that weighs 1.09 g and measures 1.7 × 1.1 × 0.9 cm. It is sectioned and half is frozen for intraoperative consultation.

2A: Frozen tissue resubmitted
2B: Remainder in toto

Central compartment and/or thymectomy specimen
The specimen identified with the patient’s name and as “central compartment” consists of a piece of fibroadipose tissue that weighs 2.5 g and measures 1.5 × 1.2 × 0.6 cm.

On section, four nodules are identified; they measure from 0.2 × 0.2 × 0.1 to 0.5 × 0.4 × 0.4 cm.

Section code
3A-D: Nodules in toto

VI. Common pathologic findings

Parathyroid biopsy
Based on the indications for parathyroid biopsy listed above, the following findings are often identified:

• Normal tissue
• Cellular parenchyma

Parathyroidectomy
Based on the indications for parathyroidectomy listed above, the following common pathologic findings are often identified:

• Adenoma
• Hyperplasia
• Carcinoma

VII. Common potential pitfalls and solutions

Parathyroid tissue is difficult to cut on frozen section, and sections often fragment or chatter. The gland normally has abundant fat, and fatty tissue is difficult to cut. Calcified lesions may require decalcification. These problems result in cracked, folded, or torn sections; sections that are missing parts of nodules; and incomplete sections that may be missing the painted resection margin. It is important for the histotechnologists to be aware of these problems to ensure the highest quality sections. It may be necessary to cut deeper levels to obtain full sections.

Occasionally, tissue is displaced during sectioning. Parathyroid tissue requires fresh and sharp blades for sectioning.

As with any other tissue, cross-contamination can be a problem. The bench must be cleaned before a new case is examined, and all instruments must be clean.

Orientation of the lesion can be problematic in complex specimens. If in doubt, the surgeon should be consulted to help with specimen orientation.

VIII. What to include in the pathology report

The final pathology report should include critical information listed by priority, although the reporting style may vary among practicing pathologists.

The details of the report should include the following:

• The main pathology identified, usually the nature of the nodule or cyst or the type of inflammatory lesion; include all relevant classifications of morphologic variant, architecture, and cytology, etc
• The location of the lesion
• The size and stage of the lesion
• The growth pattern of the lesion: infiltrative versus encapsulated, widely invasive versus minimally invasive
• Information about lymphatic invasion, angioinvasion, perineural invasion, and extrathyroidal extension
• If multiple lesions are present, identify the secondary and other pathologies
• Number of lymph nodes involved with carcinoma; how many lymph nodes were examined, and how many harbor a metastasis; the size of the largest metastatic focus
• Information about other tissues included in the specimen (eg, thyroid, thymus)
• The procedure that was performed and structures/ organs present

References

1. Wilhelm SM, Wang TS, Ruan DT, et al. The American Association of Endocrine Surgeons guidelines for definitive management of primary hyperparathyroidism. JAMA Surg. 2016;151(10):959–968.
2. DeLellis RA. Atlas of Tumor Pathology: Tumors of the Parathyroid Gland. 3rd ed. Washington, DC: Armed Forces Institute of Pathology; 1993.
3. DeLellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and Genetics of Tumours of Endocrine Organs. Lyons, France: IARC Press; 2004.

Acknowledgments, Endocrine section
The author acknowledges the contribution of photos taken by the pathologist assistants of the Department of Pathology at the University Health Network, Toronto, Ontario. Specific thanks to Mr. Martin Grealish for his assistance with the preparation of this chapter and to Dr. Ozgur Mete for his contributions to the development of the protocols and his critical review of the manuscript.