Issues with tissues: Interpreting biopsy reports (Proceedings)

Because the language of pathology originated in numerous countries and has been handed down for many generations, pathology reports are often confusing and full of misnomers. Reporting suffers from lack of standardization, canned sentences, and buried information gives rise to misunderstandings and lack of communication over pathology reports. This paper will alert you to several misnomers and misunderstandings commonly encountered by clinicians when interpreting pathology reports to anxious pet owners.

To make things worse, evidence based medicine is confounding for older and geriatric pets, especially in the field of oncology, because most published data excludes them.

Therefore the clinical trials that most generalists are expected to or are led to base their treatment decisions upon are not applicable to elderly patients! This course will assist you in the decision making process with clients regarding option

The first part of my oncology consultations is a careful review and clarification of the patient's pathology report so that the pet owner understands the actual situation and the stated prognosis. Most of the initial reports describe the tissues submitted to the pathologist by the referring doctor. Some of the samples are excisional biopsies and others are actually incisional biopsies despite the original intention of the surgeon. Over the years, I have repeatedly tangled with the threads of certain complaints in the fabric of histology reporting. I frequently wanted to formalize these "tissue issues" and commit them to print. It is my wish to help clarify, instruct and suggest improvements. It is paramount that we understand and communicate with rather than provoke an adversarial relationship with our pathologists who truly are our good friends and allies in the battle against cancer.

The "mini-histo" Often Falls Short of What is Actually Needed

Due to the high total costs involved with patients undergoing surgical oncology procedures, many veterinarians offer the less costly option for a short cut or the "mini-histo" for tissue diagnosis. Unfortunately, this short cut is too often assigned when more information is needed. Abbreviated reports generated from the "mini-histo" are not sufficient for cancer patients with owners who intend to go through the referral process. It is best for the referring doctor to call the lab and upgrade the report to a full histology report and ask the lab to send the full report directly to the consulting oncologist for the initial consultation. In my opinion, the "mini-histo" is appropriate for true cut biopsies and wedge biopsies and any other sampling biopsies needed to gain information as to tumor type and histologic grade. It is not appropriate for patients that have owners that love them enough to request "removal" of the tumor. The practitioner is theoretically engaged by the pet owner to perform an excisional biopsy (complete removal as understood by the pet owner). After the fact, the surgery may in reality only have been an incisional biopsy whereby the pet is left with an incompletely removed tumor. Unfortunately many samples are submitted that are inappropriate for determining the full status of the postoperative situation for the patient. In addition to tumor type and grade, there is a "need to know" about and report on the margins around the tumor especially if the clinician proposes to his/her client that he/she is "removing" a specific mass from their pet's body. Informed consent and informed refusal regarding the option of paying for full pathology reports are good points to recruit and openly discuss with the client. They need to know that the full pathology report plays a key role in our ability to understand the outcome of surgery.

Margins Are Essential Issues with Tissues

When evaluating the post surgical cancer patient, the oncologist needs an accurate description of the surgery along with a measurement of all margins around and below the tumor. At the time of the procedure, the gross cut margins may have been two cm but they may be reported as only one third to half of the actual operative margin. This reported disparity is due to the fact that tissues undergo shrinkage in formalin.

Practical Suggestions to Avoid Issues with Tissues

1. Always FNA a mass (to rule out MCT) prior to removing it.

2. Definitely create surgical margins around the mass that are, at the very least, the same size as the tumor itself.

3. Be certain to document the extent of the operative margins in the medical chart as part of the surgery report.

4. Send the pathologist a copy of this report with cartoon illustrations of the mass as it appears on the patient's body.

5. Mark the tissue's cranial, caudal, dorsal, ventral or deep margins with sutures or India ink. In this way you can provide orientation and a marking code for the pathologist, especially if you are working on a large tumor.

6. Do not send a large section in a small bottle! Avoid placing samples that are over one cm in thickness into the small formalin containers.

7. Make cuts into larger samples that are one cm thick; like cutting a loaf of bread into one cm slices. Leave the lowest level of tissue intact so the "loaf' stays together.

8. Use this technique for large tissue margin studies. Cut a rim of tissue from the periphery, and role it flat on a gauze pad like an onion or cinnamon role starting with the cranial end or the "noon" end on the inside of the role. Put it in formalin and send it along with samples of the mass. Send strips of tissue from the deep margin with orientation markers as well. This provides an excellent method for your pathologist to survey the peripheral cutaneous and deep margins.

9. If you don't want to prepare samples in this way, most pathologists will accept larger chilled samples if same day arrival can be arranged. Be sure to mark the sample for orientation and keep it cool or refrigerated properly during transport.

Prognosis: What Does it Really Mean?

It is not unusual to find clients in confusion and misunderstanding regarding the true meaning of their prognosis. Many clients receive the bad news over the phone or in a hasty manner at suture removal. With the ambiguity of the lingo and the variable criteria used in grading tumors by pathologists, the veterinarian may not be given a firm handle to evaluate the report for an actual or realistic prognosis. Therefore, it is not surprising that the information handed to the pet owner is blurred with ambiguity. Many pet caregivers are surprised to find out what the prognosis actually means. It is shocking to clients to learn that their pet's cancer is expected to recur, metastasize or cause death within three to six months or so if the patient remains untreated. Many pet owners suffer from acute anticipatory grief with the very mention of cancer. So it is best to present the data with a sensitive speaking manner and to acknowledge the special human-animal bond that the family shares with the patient.

Prognosis: "Fair, Guarded, Poor," veterinarians need to explain to the pet owner exactly what these words mean when it comes to their pet and the particular cancer. A phone call is generally not going to provide the client with enough information. They will go on line to find out more information about the pet's condition these days. I highly recommend that the client be scheduled a consultation appointment for delivery of biopsy report information along with downloaded handouts on the tumor type when ever available.

If the pet owner is highly emotional and not able to comprehend all the information that you must convey, ask them to bring a tape recorder or a video camera for the consultation.

In this way they can play it back to themselves for clarification and for other family members who need to know. This saves clarification phone calls and confusion.

Early in my career, I had an issue with pathologists who reported "high grade lymphoma, prognosis poor" without mentioning that it was responsive to treatment with chemotherapy. Veterinarians were justifiably confused with this type of report. We were taught to expect that a "high grade" of any type of tumor would be the worst form and therefore poorly responsive to chemotherapy. In fact, the "high grade" situation is reversed and is exactly the opposite in the case of lymphoma. It is actually the high-grade lymphomas that have the best response to chemotherapy. It is true that the pet will die in 3 weeks to 3 months in high-grade lymphoma if there is no treatment given. It is now the norm in the United States to see educational and other optimistic comments regarding responsiveness to chemotherapy woven into the fabric of most lymphoma reports.

It is appropriate to tell clients that we can't change the prognosis because a prognosis is based upon a historical group; however, the patient can "out live" the prognosis with early diagnosis and definitive treatment. This approach is appropriate for patients that are good candidates for aggressive therapy. Good decision making involves evaluation of the entire patient with their specific comorbidities and body condition score and performance score before recommending aggressive definitive cancer therapy. Please refer to the previous hour's notes on over-treatment at a veterinary cancer referral clinic for more information on decision making.

Consider it a true a practice builder to schedule a special appointment with the client to discuss the pathology report and recommendations for follow up or referral directly with the client. In this way, you will do a good job helping your client understand what the specific prognosis means and what the options are all about. Clients have commented that they got the bad news on a phone call and they did not have help in digesting the emotional impact of the situation or a chance to ask questions. Make it a policy to suggest that the client make an appointment with you on the post operative phase to discuss the biopsy report and the post surgical follow up including suture removal. If you reach out to the client and directly deliver the difficult diagnosis of malignancy during an office visit, you are performing an excellent job with communication.

When is it Right to Tell a Client that there is No Need for a Biopsy?

Cancer patients may endure one to several surgical procedures which may not yield a diagnostic biopsy. Some malignancies, by virtue of tumor necrosis and heterogeneity are notorious for not yielding diagnostic samples. We also have the scenario where the client feels that they can't afford the "extra" cost of the histopathology. In these situations, it is good to encourage the client to consider financing the biopsy at a later date. It is also a good idea to take margins which are at least the size of the mass. Save samples of the excised tumor tissue and its peripheral and deep margins in formalin. At suture removal and on rechecks, remind the client that you are holding the tissue for them. Let them know that you would still like to send their pet's tumor tissue to the pathologist for a final report whenever they are ready.

There are certain types of clinical presentations that do not need biopsy before definitive therapy is recommended. Bone cancer, splenic hemangiosarcomas, pulmonary masses, canine and feline mammary tumors and ulcerative squamous cell carcinoma of the nose, ear tips and eye lids of white sun exposed cats.

Presumptive Osteosarcoma

The diagnosis of these specific tumors is readily and reliably made based upon their specific clinical presentation. To spend patient time and client resources in order to biopsy a radiographically diagnosed bone cancer is not mandatory when we know that 98% of the bone lesions are actually osteosarcoma. A bone scan may be more beneficial to the patient especially if the lesion is long standing. Positive findings have been reported ranging from 2-7% by various groups performing bone scans. Bone scans may identify bony lesions or "hot spots" that are metastatic from the primary lesion in dogs. Cats rarely have metastatic disease in the first year from bone cancer so they do not need bone scans or biopsy prior to amputation of limbs with presumptive osteosarcoma.

Presumptive Hemangiosarcoma

For cases with presumptive ruptured splenic hemangiosarcoma, the pet owner should be advised of the overall prognosis before authorizing surgery. It is fair to explain to the pet owner that 20% of the lesions found in the bleeding spleen are not malignant on biopsy. It is important for them to know that 80% of the lesions on the bleeding spleen are highly malignant and that the average survival for the malignant cases is less than 4 months. It is good to assure the client that the of quality life following successful splenectomy is often excellent if the pet survives the surgery.

It is also fair to point out that occasionally a benign biopsy report may be erroneous because the sample may have contained only condensed hematoma and fibrinous tissue which was not representative of the actual hemangiosarcoma. One client, Gary Lloyd of Palos Verdes reversed my heavy hearted statistics about his 19 year old 90 pound collie with hemoabdomen. He rephrased my words saying, "Are you telling me that surgery will most likely give old Marty four more months to live and that he has a 20% chance to be cured and live longer than four months? Why would I not do it?"

Presumptive Cutaneous SCC or HSA

White faced cats dogs that are exposed to the sun often develop crusty, ulcerated lesions that do not heal on the face. Poorly pigmented dogs with white, glabrous skin may develop ulcerated and crusting lesions on the underbelly. It is appropriate to recommend biopsy and presume that these non healing ulcerated lesions are SCC, especially in cats. It is also appropriate to presume that multifocal red macules and blood blister-like lesions in the glabrous skin of the underbelly of white boxers and pit bull type dogs are solar induced cutaneous hemangiosarcoma. If the client declines the biopsy procedure, it is appropriate to stay focused on the potential diagnosis and offer options to treat the lesions such as cryotherapy or prescribe imiquimod (Aldara™) cream for the presumed SCC lesions. Impression smears may confirm the diagnosis with cytology, a less costly technique than surgical or punch biopsy.

Mammary Tumors

It is not necessary to do FNA or pre surgical biopsy for mammary tumors in cats because 98% are malignant adenocarcinomas. These tumors are uniformly highly aggressive. They are fatal within two years or less especially if over 3 cm in size. The entire chain should be excised with local lymph nodes and submitted for pathology. Ask the pathologist to evaluate the margins and specifically report on the axillary and inguinal lymph nodes.

It is generally not necessary to do FNA or pre surgical biopsy in canine mammary tumors because they need to be excised regardless of their tissue type. 50% of canine mammary tumors are malignant and half of those will cause the demise of the patient within 2 years. Wide removal of the mammary gland(s) involved with the local lymphatic drainage is generally adequate to yield complete margins. This author recalls one case of bilateral multiple mammary nodules in a 10 year-old West Highland Terrier where simple FNA resolved some serious issues. The clients had a consultation by a board certified surgeon who felt that the cancer was too advanced for surgery to be of help for their dog. I was consulted for a second opinion. I suggested that we perform an FNA to verify the prognosis. We found that all the nodules were fluid filled cystic lesions and on microscopic examination of the fluid we were unable to identify malignant cells.

Heart Base, CNS, Spinal Cord Tumors

For heart base tumors and CNS tumors (brain and spinal cord) a biopsy is often waived since the morbidity of obtaining a biopsy is considered too risky. Currently, UCD and others use MRI and CT as guides to biopsy brain tumors. Koblik reported 91% diagnosis with an acceptably low morbidity (epistaxis and seizures) of 12% and with low mortality of 7% in a series of 50 dogs. The biopsies found that four of the dogs in this series did not have neoplasia.

Points to Incorporate Into Daily Practice

• The "mini-histo" identifies tissue type only.

• Request margin studies for all excisional biopsies.

• Prepare samples properly for accurate determination of margins.

• Dye tissue margins with ink to orient the pathologist.

• Tag medial, lateral, proximal, distal and deep tissue samples.

• Place deep margin tissue samples in separate specimen bottles.

• Know the misnomers given to tissues and their issues.

Case presentations and actual biopsy reports will be discussed at the end of this session if time permits. These cases should help illustrate the "issues of the tissues" submitted for biopsy reports. Dr. Villalobos will make interpretations of the information provided from the reports and then make recommendations in management of special patients. Feel free to ask about your own histology reports during our discussion!

Resources

Bergman, P., Chemoprevention, Proceedings of the 1999 ACVIM Forum in Chicago.

Butler, C. and Lagoni, L., Eds., American Association of Human Animal Bond Veterinarians Newsletter, Winter 2002, p 1-12.

Choen, S. P. and C. E. Fudin, Eds. Animal Illness and Human Emotion, Problems in Veterinary Medicine, Vol. 3, No. 1 (March 1991).

Downing, R., Pets Living With Cancer: a Pet Owner's Resource, AAHA Press, April 2000.

Hoskins, J., Feline 'Triad Disease" Poses Triple Threat, D.V.M. Newsmagazine, 2-2000, p.4S-7S.

Hoskins, J., Feline 'Triad Disease' not Breed or Sex Specific, D.V.M. Practice Builder, 10-2000, p. 31-35.

Hunt, L.E., Angel Paw Prints: An Anthology of Pet Memorials, Darrowby Press, 1998.

Lagoni, L., Morehead, D., Butler, C., The Bond-Centered Practice: The Future of Veterinary Care, Proceedings of the 1999 ACVIM Forum in Chicago.

MacEwen, E. G., Withrow, S. T., Small Animal Clinical Oncology, Third Edition, W.B. Saunders Company, 2001.

Martin, E. C., Dr. Johnson's Apple Orchard, The Story of America's First Pet Cemetery, 1997, Image Graphics Inc., Paducah, KY.

Ogilvie, G.K., Hospice and Bond Centered Practice: The Future of Veterinary Care, Proceedings of the 1999 ACVIM Forum in Chicago.

Ogilvie, G.K., Moore, A.S., Managing the Veterinary Cancer Patient: A Practice Manual, Veterinary Learning Systems, 1995.

Rawlings, JAAHA, 1993, 29: 562-530, Percutaneous Placement of a Midcervical Esophagostomy Tube: New Technique and Representative Cases.

Villalobos, A., Oncology Outlook, Those Stubborn Cats That Won't Eat, 8-1999.

Villalobos, A., Oncology Outlook, Pet Hospice Nurses the Bond, VPN, 9-1999.

Villalobos, A., Oncology Outlook, On Bladder and Prostate Cancer, VPN, 1-2000.

Villalobos, A., Oncology Outlook, Chemoprevention: Can Food Fight Cancer? VPN, 3-2000, p. 48.

Villalobos, A., Cancer: Early Diagnosis Offers Hope, D.V.M. News Magazine, Practice Builder Supplement, 10-2001, p. 10-14.

Book Resources

Canine and Feline Geriatric Oncology: Honoring the Human-Animal Bond, by Alice Villalobos, DVM, with Laurie Kaplan, MSC, Wiley-Blackwell Publishing, Hoboken, NY, 2007.

Small Animal Clinical Oncology, 3rd & 4th Edition, Dr. Stephen Withrow, David Vail and the late Dr.Gregory MacEwen, eds., Saunders/Elsevier, 2001 & 2007.

Managing the Veterinary Cancer Patient, A Practice Manual, Feline Oncology

By Gregory Ogilvie and Anthony Moore, Veterinary Learning Systems

Professional Websites

www.VIN.com, VINGRAM@VIN.com , Veterinary Information Network hosted by Dr. Paul Pion

www.vetmed.lsu.edu/oncology, contributed by Drs. Neal and Glenna Mauldin

www.vetcancersociety.org, Veterinary Cancer Society

www.oncurapartners.com, Oncura Partners™ provides online consultants to veterinarians and will sell unit dose pharmaceuticals for enrolled patients as part of their professional services.

www.blackwell-science.com/vco, Veterinary and Comparative Oncology, journal of the VCS.