Last updated May 1998

Adrenal Gland

Protocol applies to malignant adrenal cortical tumors and pheochromocytomas.  Neuroblastoma and other adrenal medullary tumors of childhood are excluded.

Procedures

• Cytology

• Incisional Biopsy

• Excisional Biopsy

• Adrenalectomy

I. Cytologic material            back     Top     Main Page

A.  CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Identification number

c.   Age (birth date)

d.   Gender

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (Note A)

b.   Relevant findings (e.g., hormonal and imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g., FNA)

e.   Anatomic site(s) (e.g., right/left adrenal, related sites)

B. MACROSCOPIC EXAMINATION

1.   Specimen

a.   Unfixed/fixed (specify fixative)

b.   Number of slides received

c.   Quantity and appearance of fluid specimen

d.   Other (e.g., cytologic preparation from tissue)

e.   Results of rapid smear review

2.   Material submitted for microscopic evaluation (e.g., direct smear, cytocentrifuge preparation, touch or filter preparation, cell block)

3.   Special studies (Note C)

C. MICROSCOPIC EVALUATION

1.   Adequacy of specimen (if unsatisfactory for evaluation, specify reason)

2.   Tumor, if present

a.   Histologic type, if possible (Note D)

b.   Other descriptive features (e.g., nuclear atypia, necrosis)

3.   Additional pathologic finding, if present

4.   Results/status of special studies (specify) (Note C)

5.   Comments

a.   Correlation with intraprocedural consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c.   Correlation with clinical information, as appropriate

II. Incisional biopsy             back     Top     Main Page

(any surgical approach less than complete adrenal excision)

A. CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Identification number

c.   Age (birth date)

d.   Gender

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (Note A)

b.   Relevant findings (e.g., hormonal and imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g., fine needle biopsy, core biopsy, incisional biopsy)

e.   Operative findings

f.    Anatomic sites (e.g., right/left adrenal, related sites)

B. MACROSCOPIC EXAMINATION

1.   Specimen

a.   Organ(s)/tissue(s) (specify)

b.   Unfixed/fixed (specify fixative)

c.   Number of fragments

d.   Dimensions

e.   Weight, if appropriate

f.    Orientation (if indicated by surgeon)

g.   Descriptive features

h.   Results of intraoperative consultation

2.   Tumor(s), if identified

a.   Location

b.   Dimensions (three)

c.   Descriptive features (e.g., hemorrhage/necrosis)

d.   Relationship to margins, if appropriate

3.   Additional pathologic findings, if present (e.g., hyperplasia)

4.   Tissue submitted for microscopic evaluation

a.   Tumor

b.   Margin(s), if appropriate

c.   Nodules

d.   Other lesions

e.   Frozen section tissue fragment(s) (unless saved for special studies)

5.   Special studies (specify ) (Note C)

C. MICROSCOPIC EVALUATION

1.   Tumor, if present

a.   Histologic type (Note D)

b.   Descriptive features (e.g., nuclear atypia, necrosis)

c.   Blood/lymphatic vessel invasion

2.   Additional pathologic findings, if present  (e.g., hyperplasia)

3.   Results/status of special studies (specify) (Note C)

4.   Comments

a.   Correlation with intraoperative consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c.   Correlation with clinical information, as appropriate

III. Complete excision                  back     Top     Main Page

 (including laparoscopically removed glands)

A. CLINICAL INFORMATION

1.   Patient identification

a.   Name

b.   Identification number

c.   Age (birth date)

d.   Gender

2.   Responsible physician(s)

3.   Date of procedure

4.   Other clinical information

a.   Relevant history (Note A)

b.   Relevant findings (e.g., hormonal and imaging studies) (Note B)

c.   Clinical diagnosis

d.   Procedure (e.g., laparoscopically removed gland) (Note F)

e.   Operative findings

f.    Type of specimen (adrenal excision with or without surrounding soft tissues)

g.   Anatomic site(s) of specimen (e.g., right/left adrenal, related sites)

B. MACROSCOPIC EXAMINATION

1.   Specimen

a.   Organ(s)/tissue(s) included

b.   Unfixed/fixed (specify fixative)

c.   Dimensions (three)

d.   Weight

e.   Orientation (if indicated by surgeon)

f.    Descriptive features

g.   Results of intraoperative consultation (Note C)

2.   Tumor(s)

a.   Dimensions (three)

b.   Weight (Note G)

c.   Descriptive features (e.g., color/consistency/hemorrhage/necrosis)

d.   Extent of invasion (Note H)

3.   Margins, relationship to and distance from tumor (as appropriate)

4.   Regional lymph nodes (if submitted)

a.   Number

b.   Location (if designated by surgeon)

5.   Additional pathologic findings, if present

6.   Tissue(s) submitted for microscopic evaluation

a.   Tumor, adequate sampling of all areas

b.   Nodules

c.   Margins of resection

d.   All lymph nodes

e.   Other lesions

f.    Frozen section tissue fragment(s) (unless saved for special studies)

g.   Other organs/tissues (e.g., liver biopsy)

7.   Special studies (specify) (Note C)

C. MICROSCOPIC EVALUATION

1.   Tumor

a.   Histologic type (Note D)

b.   Descriptive features (e.g., nuclear atypia /mitotic rate/necrosis) (Note E)

c.   Extent of invasion (Note H)

d.   Blood/lymphatic vessel invasion

2.   Margins (as appropriate)

3.   Regional lymph nodes (Note H)

a.   Number (location, if possible)

b.   Number involved by tumor

4.   Additional pathologic findings, if present (e.g., hyperplasia)

5.   Result/status of special studies (specify) (Note C)

6.   Other organs/tissues

7.   Comments

a.   Correlation with intraoperative consultation, as appropriate

b.   Correlation with other specimens, as appropriate

c.   Correlation with clinical information, as appropriate

EXPLANATORY NOTES

A. Relevant History             back     Top     Main Page

Endocrine manifestations, such as hypertension, change in body habitus, feminization or virilism, are important. Also of importance are family history, previous surgery for adrenal tumors (both benign and malignant) or other endocrine organs, other tumors which may metastasize to the adrenal gland, and endocrine or other therapies. Incompletely removed hyperplastic adrenal tissue may re-grow if previously incompletely excised.

B.  Endocrine Status          back     Top     Main Page

Laboratory findings are important in the evaluation of an adrenal mass because the absence of evidence of hormonal excess in the presence of an enlarged adrenal that is not obviously a high grade carcinoma usually indicates that the tumor is an incidental finding (“incidentaloma”) and not a functioning adenoma.(1)

 

C. Special Procedures                back     Top     Main Page

Special procedures may include: frozen sections, cytologic imprints, immunohistochemical stains, histochemical stains, electron microscopy, flow cytometry, molecular studies and cytogenetic studies.  If such studies are performed in another laboratory, either extra-institutional or intra-institutional, the laboratory should be identified.

D. Histologic Type              back     Top     Main Page

The following histologic classification of adrenal tumors has been modified from Page et al.(2)

Histologic Classification of Adrenal Tumors

• Cortical Tumors

-Adenoma

-Carcinoma

-Myelolipoma

-Miscellaneous

• Medullary Tumors

-Pheochromocytoma

-Neuroblastoma

-Ganglioneuroblastoma

-Ganglioneuroma

E. Histologic Grade             back     Top     Main Page

Adrenal cortical tumors are not usually graded on histologic grounds. Severe nuclear atypia, high mitotic count, vascular invasion, tumor necrosis, and other microscopic features may, in combination, support a diagnosis of adrenal cortical carcinoma over adenoma and should be recorded, but no precise clustering of histologic features is considered diagnostic of malignancy. However, when several malignant features are present together (e.g., highly atypical nuclei, sheet-like growth, necrosis and many mitoses) the risk of distant metastases is increased.(3-6)  In some studies, specific combinations of features such as mitotic rates of 6 or more per 50 HPF along with atypical mitosis and venous invasion have been found to correlate with metastasis or recurrence of adrenal cortical carcinomas.(4) Other studies have shown that mitotic rates greater than 20 per 50 HPF are associated with decreased survival,(5) suggesting that a high mitotic index may be an important adverse prognostic factor.(5)

 

Pheochromocytoma is usually diagnosed preoperatively by pharmacologic means. No pathologic criteria for differentiation of benign from malignant pheos have been defined. Metastatic disease is considered the only irrefutable proof of malignancy.

F. Laparoscopic Surgery            back     Top     Main Page

An entire adrenal tumor may be removed laparoscopically, but with this technique, the gland may become fragmented. This anatomic information, including maximal diameter of the resected tumor, should be provided by the surgeon.

G. Weight           back     Top     Main Page

Accurate weights of adrenal cortical neoplasms are important.(6) Although tumor mass cannot be used as the sole criterion for malignancy, adrenal cortical neoplasms weighing less than 50 grams are almost always benign, whereas the weight of malignant tumors is usually greater than 100 grams.

H. Staging          back     Top     Main Page

The staging system proposed by MacFarlan(7) and modified by Sullivan et al and Henley et al(8,9) is most commonly used for adrenal cortical carcinomas. The American Joint Committee on Cancer/International Union Against Cancer has no published TNM staging system for malignancies of the adrenal gland.

STAGE        EXTENT                           SIZE

I                    Confined to gland             < 5 cm

II                    Confined to gland             > 5 cm

III                   Extends out of gland         Any without involving adjacent organs

IV                  Distant metastasis           Any or involvement of adjacent organs

The AFIP Fasicle of the Adrenal Gland and Extra-Adrenal Paraganglia(10) proposes the following staging system:

Primary Tumor (T)

T1        Tumor < 5 cm, no invasion

T2        Tumor > 5 cm, no invasion

T3        Tumor of any size, locally invasive but not involving adjacent organs

T4        Tumor of any size with invasion of adjacent organs

 

Regional Lymph Nodes (N)

N0       Negative regional nodes

N1       Positive regional nodes

Distant Metastasis (M)

M0       No distant metastasis

M1       Distant metastasis

Stage Definitions

Stage I         T1           N0             M0

Stage II        T2           N0             M0

Stage III       T1           N1             M0

                     T2           N1             M0

                     T3           N0             M0

Stage IV      Any T     Any N       M1

                     T3           N1             M0

                     T4           N1             M0

REFERENCES            back     Top     Main Page

1.         Kloos RT, Gross MD, Francis IR, Dorobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocrine Reviews. 1995; 16:460-484.

2.         Page DL, DeLellis RA, Hough AJ Jr. Tumors of the Adrenal; Atlas of Tumor Pathology, 2nd Series, Fascicle 23, Armed Forces Institute of Pathology, Washington, DC, 1986.

3.         Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenocortical tumors: A mathematical analysis of clinical and morphologic data. Am J Clin Pathol. 1979; 72:390-399.

4.         Weiss LM. Comparative histologic study of 43 metastasizing and non-metastasizing adrenocortical tumors. Am J Surg Pathol. 1984; 8:163-169.

5.         Weiss LM, Medeiros LJ, Vickery AL. Pathologic features of prognostic significance in adrenal cortical carcinoma. Am J Surg Pathol. 1989; 13:202-206.

6.         Medeiros LJ, Weiss LM. New developments in the pathologic diagnosis of adrenal cortical neoplasms. A review. Am J Clin Pathol. 1992; 97:73-83.

7.         MacFarlane DA. Cancer of the adrenal cortex: The natural history, prognosis, and treatment in a study of fifty-five cases. Ann R. Coll Surg Engl. 1958; 23:155-186.

8.         Sullivan M, Boileau M, Hodges CV. Adrenal cortical carcinoma. J Urol. 1978; 120:660-665.

9.         Henley DJ, van Heerden JA, Grant CS, Carney JA, Carpenter PC. Adrenal cortical carcinoma— A continuing challenge. Surgery. 1983; 94:926-931.

10.  Lack E. Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia.  AFIP Fasicle No. 19, Third Series.  American Registry of Pathology, Washington D.C. 1997.

BIBLIOGRAPHY

Dehner LP. Neoplasms of the adrenal cortex. Preoccupation bordering on obsession [editorial; comment]. Editorial. Am J Clin Pathol. 1994; 101:557-558.

Katz RL, Patel S. Mackay B, Zornoza J. Fine-needle aspiration cytology of the adrenal gland. Acta Cytol. 1984; 28:269-282.

Pathology of the Adrenal Glands, Lack EE, ed. Contemporary Issues in Surgical Pathology. Churchill Livingstone, NY. 1990.

Lloyd RV. Endocrine Pathology. Springer-Verlag, NY, 1990.

Authors

David L. Page, MD and Stephen G. Ruby, MD

Contributors:             back     Top     Main Page

CAP Cancer Committee; Edward Paloyan, MD; Geoffrey Smoron, MD; Ronald A. DeLellis, MD; Ernest E. Lack, MD