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Pediatric Tumors : Surgical Pathology Dissection

Pediatric Tumors : Surgical Pathology Dissection
A number of tumors are unique to children. These tumors frequently require special processing to ensure that the diagnosis can be established and appropriate treatment given.

Pediatric Tumors

General Comments

A number of tumors are unique to children. These tumors frequently require special processing to ensure that the diagnosis can be established and appropriate treatment given. The Children’s On-cology Group (COG) creates, monitors, and eval-uates therapeutic protocols for pediatric tumors. In the United States, COG frequently requires that pathologic material be sent to review patholo-gists to verify the diagnosis and to further classify the tumor. Additional fresh and frozen tissue is often required for biologic studies, which are performed at specialized reference laborato-ries. If this tissue is not collected at the time of surgery, the patient may not be eligible for the appropriate treatment protocol. Furthermore, as knowledge is accumulated and protocols change, tissue requirements change. Therefore, patholo-gists who are processing pediatric tumors need to work closely with their pediatric oncologists to be aware of the current protocol requirements. Conversely, the entire specimen cannot be submitted for biologic studies. Sufficient tissue must be available to establish a histologic diag-nosis. It is vital that the pathologist be respon-sible for the appropriate triage of this tissue. In many cases, tissue also needs to be submitted for ancillary diagnostic studies (such as electron microscopy and cytogenetic analysis). Despite these demands, pediatric tumors can be pro-cessed easily if a series of steps is routinely performed at the time of initial processing. Establishing a routine is particularly important because many biopsies are performed during off-hours.

Overall Guidelines

1. Ensure that all pediatric tumors are promptly received in the fresh state. This may entail pro-cessing during off-hours by on-call personnel.

2. Decide how much of the specimen is needed for routine histology. This will depend on the tumor type suspected and the size of the biopsy.

3. Submit tissue for electron microscopy if appro-priate. It is good practice to put a small piece of every pediatric tumor in glutaraldehyde. This can then be embedded, and the decision of whether to section and process can be made at a later time.

4. Place 1/2 to 1 cc of minced tumor in Roswell Park Memorial Institute medium (RPMI) or equivalent tissue culture medium and refrig-erate. This material can be submitted for cyto-genetic analysis, flow cytometry, or mailed to a reference laboratory for special studies (such as ploidy, gene amplification studies, or fluo-rescence in situ hybridization).

5. Freeze a minimum of 1 cc of tumor tissue in liquid nitrogen. This can be submitted to refer-ence laboratories for protocol studies or held locally in a tumor bank if available. Normal tissue should also be frozen. If you have lim-ited tissue, remember that the frozen section control is often inadequate for permanent his-tology, yet if it is kept frozen it can be used for these studies.

Small Blue Cell Tumors of Childhood

Pediatric tumors are often embryonal neoplasms showing little or no differentiation by routinehistology. In particular, at the time of frozen sec-tion, these tumors appear to be primitive, small, round blue cell tumors. Their diagnosis often depends on ancillary studies such as immuno-histochemistry, electron microscopy, and cyto-genetics or molecular genetic analysis. If all pediatric specimens are processed as delineated in the first section, all necessary information should be available in a timely fashion. Table 39-1 lists the most common small blue tumors of child-hood and their pertinent diagnostic features.


Pediatric Renal Neoplasms

Pediatric renal tumors are often primarily re-sected and must be carefully processed to en-sure accurate staging.19Since these tumors are often bulky and friable and are therefore easily distorted, processing must be undertaken with care.

1. Photograph the nephrectomy specimen before bivalving. Carefully examine the contour of the kidney and the tumor, and identify poten-tial sites of capsular penetration.


2. Ink the surface (do not strip the capsule).


3. Submit shave sections of the vascular and ure-teral margins. The renal vein margin is particu-larly important.


4. Bivalve the specimen. The kidney should always be bivalved by the pathologist after steps 1–3 are performed, not by the surgeon and not in the operating room. Choose your plane of incision carefully, as the placement of the origi-nal incision determines your ability to docu-ment the relationship between the tumor and kidney, the tumor and the renal sinus, etc. The incision should be at or near the vertical mid-plane of the kidney. This cut should avoid sites of capsular penetration if possible.


5. Obtain fresh tissues needed for special studies (cytogenetics, frozen, etc.), as outlined pre-viously. Photograph the bivalved specimen.


6. Make cuts parallel to the initial bivalving inci-sion at 2- to 3-cm intervals. Submerge the spec-imen in a large container of formalin. If the formalin can be refrigerated, color preserva-tion will be enhanced and autolysis slowed.


7. After a few hours or overnight fixation, the remaining sections may be obtained. Two slides should be prepared from all tissue blocks to expedite the mailing of slides to the external review pathologist. The majority of the routine tumor sections should be taken from the periphery of the lesion, showing the following:

a. Nature of the tumor–kidney junction.

b. Relationship of the tumor to the renal capsule, particularly in areas of concern for capsular penetration.

c. Relationship of the tumor to the renal sinus.

d. Areas of the tumor that appear different (e.g., necrosis, hemorrhage). Always in-dicate the exact site from which each sec-tion is taken. This is most easily done by taking Polaroid or digital photographs. Drawings are often insuf-ficient.


8. Carefully section and inspect the normal kid-ney, particularly adjacent to the tumor. These areas may show microscopic foci of persis-tent embryonal tissue known as nephrogenic rests, the potential precursor lesion of nephro-blastomas.


9. Carefully dissect the hilar and perinephric tissues for lymph nodes. Failure to submit re-gional lymph nodes may render patients ineli-gible for some low-stage protocols.


Using the above guidelines for submission of blocks, histologic evaluation should then pro-vide the specific tumor diagnosis as well as the stage. The staging currently used for pediatric tumors is provided in Table 39-2.

 The diagnosis of stage II neoplasms depends on the identifica-tion of either renal capsular penetration or in-vasion of vessels of the ‘‘renal sinus.’’ The renal sinus is the principal portal of exit for tumor cells from the kidney and therefore deserves careful study. The renal sinus is the concave portion of the kidney that contains much of the pelvicalyceal system and the principal arteries, veins, lymphat-ics, and nerves that pass through this sinus. It is largely filled with vascularized adipose tissue. The renal sinus can be recognized histologically by the fact that the renal cortex lining the sinus lacks a capsule. A thick capsule surrounds the pelvicalyceal structures and continues to cover the medullary pyramids. The distinction between stage I and stage II tumors includes either pene-tration of the renal capsule or infiltration of ves-sels of the sinus. Some stage I tumors can distort the renal sinus and protrude with a smoothly encapsulated surface without invading the soft tissue of the renal sinus. Such tumors do not meet the criteria for upstaging, unless they show renal capsular penetration.

Important Issues to Address in Your Report on Pediatric Renal Neoplasms

What procedure was performed, and what structures/organs are present?



What type of neoplasm is present? The most common diagnoses in children are Wilms tumor, clear cell sarcoma of kidney, rhabdoid tumor, congenital mesoblastic nephroma, and renal cell carcinoma. If Wilms tumor, state whether the histology is favorable or unfavor-able. Unfavorable histology is based on the pres-ence of cells with nuclei four times the size of surrounding blastemal cells and the presence of aberrant, multipolar mitotic figures. If unfa-vorable histology (also called anaplasia) is pres-ent, comment on its extent (focal or diffuse).


What is the size of the tumor (weight and greatest dimension)?


Are any margins involved?


Is the renal vein involved by tumor?


Is renal capsular penetration present?


Is renal sinus invasion present?


Has the tumor metastasized to regional lymph nodes? Record the number of metastases and the total number of lymph nodes examined.

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