Sr-90 Radiation Therapy for Uropygial Neoplasia by Dr. Nemetz

Strontium-90 Therapy for Uropygial Neoplasia

Presenting Author: Larry P. Nemetz, DVM

Co-Author: Michael Broome, DVM , MS , Dipl ABVP (Companion animal)

This procedure is available for any histologically confirmed clinical case of primary uropygial neoplasia from any referral veterinarian in the United States. Please call the clinic for pricing.

Dr. Nemetz is also interested in any case of testicular or renal neoplasia, especially diagnosed in Budgerigars where this radiation therapy might be applicable.

Please have your veterinarian call The BIRD clinic for more details and requirements:

(714) 633 - 2910 or FAX histopathology and history to (714) 633 - 2905.

This is the exact manuscript submitted to AAV by Dr. Nemetz. References are left out to conserve space.

Affiliation: From The BIRD Clinic Veterinary Corporation, 2525 North Grand Ave, Suite R, Santa Ana, CA 92705, USA (Nemetz) and Advanced Veterinary Medical Imaging, CA 92780, USA (Broome)            

Abstract: A carcinoma and squamous cell carcinoma of the uropygial gland was diagnosed in 2 budgerigars ( Melopsittacus undulatus). A papillary adenoma of the uropygial gland was diagnosed in a cockatiel ( Nymphicus hollandicus). Surgical excision had been the main therapy for uropygial neoplasia but with variable success. A single irradiation fraction of 100 Gy/8.3 mm from a Strontium-90 ophthalmic applicator with or without surgical debulking was presented as a simple, viable, non-invasive method at moderate cost for the successful treatment of uropygial neoplasia.

Key words: neoplasia, uropygial gland, carcinoma, adenoma, radiation

Introduction

The uropygial gland is a bilobed gland located at the base of the tail dorsal to the pygostyle. It is absent in many Columbiformes, Amazon parrots, and some other Psittaciformes.1 Adenomas, adenocarcinomas, and squamous cell carcinomas (SCC) are recognized neoplastic abnormalities of the uropygial gland.1,2 Differential diagnosis of an abnormal swelling of the uropygial gland must include adenitis, hypovitaminosis A with glandular metaplasia and hyperkeratosis, abscessation, and impactions.1,2 Neoplasia often distorts the normal architecture of the gland, but a definitive diagnosis should be confirmed by tissue biopsy. In avian medicine, surgical excision has been the main therapy for uropygial neoplasia.1,3 The uropygial gland has an expansive blood supply with the gland itself extending deeply from the synsacrum to the insertion point of the tail feathers.1 Surgical complications include hemorrhage, post surgical dehiscence, infection, risk of vascular metastasis, and failure to achieve neoplastic free margins.

Strontium-90 (Sr-90) radiation has been used since 1950 in humans for the treatment of localized neoplasms of the orbit: pterygia4,6,7 and conjunctival lymphoma.5 A Sr-90 ophthalmic probe was used for a conjunctival squamous cell carcinoma in an umbrella cockatoo (Cacatua alba),1 to treat early squamous cell carcinoma of the nasal planum in cats,8 and shown to have long term benefits in the treatment of corneal pannus (superficial vascularization) in the dog.9 In these three reports, we determine the efficacy and toxicity of Strontium-90 plesiotherapy for the treatment of uropygial neoplasia in the bird.

Background of strontium-90 

Radioactive Sr-90 is produced as a fission by-product of uranium and plutonium and is not a stable isotope.10 It was produced mostly during nuclear weapons tests conducted in the 1950's and 1960's.10 Strontium-90 has a half-life of 28.78 years.8,10 It emits beta particles of relatively low energy as it decays to Yttrium-90 which emits beta particles of higher energy.10 The magnitude of health risk depends on the exposure conditions of dose and time represented as Gray (Gy) or equivalent 100 roentgen absorption dose (rad).10,11 Ophthalmic applicators were manufactured with limited tissue penetration mainly to treat pterygia or tumors of the orbit in humans.4-6,7

Materials and Methods

A Sr-90 Ophthalmic Applicator (Atlantic Research Corp) manufactured in 1953 was used for each case. The active source diameter measured 8.3 mm with an outer probe diameter of 10.3 mm.11 The maximum surface absorbed dose rate to water (tissue) was 0.25 Gy (25 rads)/s.11 A single fraction of 100 Gy (0.25 Gy/s x 400 seconds) / 8.3 mm field was chosen empirically from dose ranges used on the human orbit of 30 - 80 Gy4,5,7 to 200 Gy for squamous cell carcinoma of the nasal planum in cats.8 A lower dose was used weighing the following facts: radiation is cumulative, subsequent fractions were an option, and stratified squamous cell epithelium is more resistant to radiation penetration compared to non-stratified squamous cell epithelium.

Three birds were selected, each representing a different neoplasm of the uropygial gland. Each bird was induced and maintained under anesthesia with isoflurane and placed on a Plexiglas plate. The Plexiglas prevents the creation of penetrating high-energy short wavelength x-rays resulting from beta particle exposure to any metal surface. The ophthalmic probe was applied to the surface of the neoplasia and held in place using a clamp stand during the dosing cycle.

Case Reports

Case 1

A 5.5-year-old, 37-g male budgerigar ( Melopsittacus undulatus) was presented for examination of a hemorrhaging dorsal tail area. There was no history of trauma to the bird and it otherwise appeared in good physical condition. A 10 x 10 x 6-mm mass was observed extending from the location of the uropygial gland. The central area of the mass was ulcerated and covered with dried blood. The mass increased in size to 12 x 13 x 9-mm over six days while the owner decided on further diagnostics.

A complete blood count (CBC) was performed. The PCV was 31, WBC 6,000, and the total serum solids (TSS) were 2.6 mg/dl. A 2-mm dermal punch biopsy was obtained from the growth's non-ulcerated region with subsequent hemostasis. The bird was fitted with a cervical collar to prevent self-mutilation. Histologic examination revealed an infiltrative unencapsulated neoplasm comprised of irregular trabeculae that were occasionally branching and were comprised of asynchronous maturing squamous epithelial cells. There were foci of keratin pearls, some of which were mineralizing within the trabeculae. The lining cells were numerous and closely placed with a more basophilic cytoplasm. The mitotic rate was moderate at 3-4 per high power field. A diagnosis of uropygial gland carcinoma was made.

Surgical excision was considered, but with the low PCV and risk of further hemorrhaging Sr-90 therapy was chosen. The uropygial carcinoma was treated with a single fraction of 100 Gy/8.3 mm. Three fields were required to cover the area of the neoplasm and surrounding margins. The procedure induced no acute or subsequent effects in the bird.

The bird was presented 48 hours post Sr-90 therapy for examination. The central core of the neoplasm slough leaving a necrotic center but no hemorrhaging. The bird was rechecked weekly. At three weeks post therapy the area had fully healed and the gland resumed oil production. The area remains unchanged nine months post radiation therapy.

Case 2

A 5-year-old, 55-g female budgerigar ( Melopsittacus undulatus) was presented for examination of a large mass extending from the dorsal tail region. The bird was markedly obese. A pediculation arising from the uropygial gland papillae demonstrated a 3-mm stalk terminating in a 15 x 12 x 10-mm mass. The owner declined blood work, but agreed to surgical amputation at the pedicle and histopathology.

Histologic examination revealed an infiltrative unencapsulated neoplasm comprised of clusters to individualized nests and trabeculae of neoplastic squamous epithelial cells. There was asynchronous maturation with a mitotic rate low at 1-2 per high power field. A diagnosis of uropygial gland squamous cell carcinoma was made.

Sr-90 therapy was scheduled fifteen days from original presentation. The uropygial gland squamous cell carcinoma was treated with a single fraction of 100 Gy/8.3 mm. A single field centered over the area of the pedicle was used. The procedure induced no acute or subsequent effects in the bird.

The bird was checked weekly for the first six weeks and appears free of pathology eight months post radiation therapy.

Case 3

A 6-year-old, 113-g female cockatiel ( Nymphicus hollandicus) was referred for a 15 x 9 x 8-mm mass growing out of an ulcer in the epidermis covering the left lobe of the uropygial gland. Examination revealed marked obesity, color changes to most of the contour feathers, and confirmation of a papillar mass of the left lobe of the uropygial gland extending subcutaneously toward the right lobe. A 4-mm dermal punch biopsy of the papillary projection was obtained with minimal hemorrhage.

Histologic examination revealed irregular proliferations of uropygial glands. The glands were well differentiated but formed multiple branching projections of the glands. There was normal maturation and exfoliation of cells within the lumen of the glands.  The projections were supported by large dense aggregates of keratin that had populations of small yeast. A diagnosis of uropygial gland papillary adenoma with hyperkeratosis and yeast proliferation was made. The yeast organisms were identified as most consistent with Malassezia.

Sr-90 therapy was scheduled five weeks after initial presentation. The uropygial gland adenoma was treated with a single fraction of 100 Gy/8.3 mm. Two fields were required to cover the area of the neoplasm and surrounding margins. The procedure induced no acute or subsequent effects in the bird.

The bird was checked weekly for the first four weeks, then monthly. The neoplasm continues to undergo cellular necrosis and epithelization during each subsequent week. At eight weeks post treatment the area of the neoplasm continues to regress.

Discussion

The uropygial gland is unique to some avian species. Uropygial neoplasia has been well recognized.1,2 In avian species, surgical excision has been the mainstay of cancer treatment, namely because most radiotherapy and chemotherapy regimens are cost prohibitive to pet owners or may result in significant patient morbidity.3 Other forms of radiation, Cesium-137 and orthovoltage, have been used for avian neoplasms but often require ten or more fractions over several weeks.3

Long term studies using Sr-90 in humans to treat pterygia and conjunctival lymphoma have shown excellent results, long term remission, and minimal complications.4,5 Similar applications of Sr-90 in the dog9 and cat8 have demonstrated positive long term benefits and minimal side effects.

The results of this report indicate that Strontium-90 beta-ray plesiotherapy is also effective in birds for treating neoplasia of the uropygial gland. Treatment should be limited to shallow lesions because the 50% isodose line corresponds to a depth of 2 mm for most applicators.8 Surgical debulking of large neoplasms may be indicated prior to Sr-90 plesiotherapy. Response time after therapy is directly related to the mitotic activity of the neoplasm; the higher the mitotic rate the faster the response time. Sr-90 treatment is convenient, has minimal patient risk, minimal toxicity, and is less costly compared to surgical extirpation of the gland or other forms of irradiation.

Availability of a Sr-90 Ophthalmic Applicator is restricted to persons that possess a State radioactive materials license or a Federal license by the National Regulatory Commission: medical research hospitals, veterinary medical teaching hospitals, veterinary/human oncologists, radiologists, or ophthalmologists. The procedure must be performed based on safety guidelines for radiation safety protocols at that facility. Cost determination includes anesthesia, the use of the Sr-90 applicator, and professional services. No hospitalization or medications are necessary in this procedure.