Jennifer C. Olson, DVM; Gary D. Norsworthy, DVM, Diplomate ABVP (Feline); & J. Scot Estep, DVM, Diplomate ACVP
This article describes clinical signs, laboratory diagnostics, imaging, and cytologic analysis for a cat with progressive nonpruritic dermatologic changes, inappetence, decreased water consumption, and recent anorexia. Can you determine the diagnosis?
A 14-year-old spayed female domestic medium-hair cat was referred for evaluation of progressive nonpruritic dermatologic changes, inappetence, and decreased water consumption over 4 weeks; anorexia had developed in the past week.
PHYSICAL EXAMINATION
Upon presentation the cat had a body condition score of 4/9 and weighed 3.82 kilograms. The cat was euhydrated and, based on records from the referring veterinarian, had lost 1.32 kg during the past 12 months. No signs of excessive grooming were reported by the owner.
Clinical examination findings included shiny, symmetrical alopecia on the ventral abdomen and chin, periocular alopecia and inflammation, perionychitis, and easily epilated hair (Figures 1–3).
Figure 1. Shiny symmetrical alopecia on the ventral abdomen, with easily epilated surrounding hair.
Figure 2. Perionychitis
Figure 3. Shiny alopecia on the chin, with easily epilated surrounding hair.
DIAGNOSTICS
Laboratory Analysis
Diagnostics performed the day prior to referral revealed elevated BUN, normal creatinine, mild eosinophilia, and mild hyperglycemia (Table 1). These biochemical and hematologic abnormalities were nonspecific and clinically insignificant.
Imaging
Abdominal ultrasound identified multiple hypoechoic masses in the liver (Figure 4). The pancreas could not be identified due to gas acoustic impedance. The remainder of the ultrasound study was unremarkable. Thoracic radiographs were normal.
Figure 4. Ultrasound image showing heterogeneous hypoechoic mass.
Cytopathology
Under sedation, fine-needle aspiration biopsy samples were collected from a hepatic mass using ultrasound guidance. The findings are listed in Table 2.
 
PRESUMPTIVE DIAGNOSIS
The vague acini led the pathologist to suspect biliary or pancreatic origin, but there were not enoughfeatures for definitive diagnosis. However, this information, in context of the clinical picture, led to a presumptive diagnosis of hepatobiliary adenocarcinoma and feline paraneoplastic alopecia. Based on the presumptive diagnosis and prognosis, the owners elected euthanasia.
POSTMORTEM DIAGNOSTICS
Gross Pathology
Significant gross pathologic findings at necropsy included numerous multifocal soft pale hepatic nodules (Figures 5 to 7) while the lung, pancreas, and intra-abdominal lymph nodes appeared grossly normal.
Figure 5. Appearance of liver when opening the abdomen during necropsy.
Figure 6. Hepatic nodules in section.
Figure 7. Necropsy image of the pancreas with no gross pathology.
Histology
- Histopathology revealed glandular and solidly cellular areas that had replaced most of the pancreas and aggressive invasion of the tumor into the liver and lungs (Figures 8 to 10).
- Immunohistochemistry of the neoplastic cells was positive for pancytokeratin, cytokeratin 7, cytokeratin 20, vimentin, and negative for TTF-1, synaptophysin, chromogranin, and calcitonin. These markers were designed to differentiate primary from metastatic hepatic neoplasia, and the results supported a differential of cholangiocarcinoma or pancreatic carcinoma, while ruling out thyroid, pulmonary, thymic, and neuroendocrine neoplasia.
- Dermatohistopathology revealed a mostly eroded stratum corneum, with some focal areas of parakeratosis, moderate to severe acanthosis, and telogenized hair follicles, which were diffusely miniaturized (Figure 11). Sebaceous glands were unaffected and appeared enlarged.
According to the World Health Organization tumor staging for pancreatic tumors in domestic animals,1 this patient was classified as T1 N0 M1 (Table 3).
Figure 8. Histopathology of pancreatic adenocarcinoma (40x) with near complete replacement by neoplastic cells. The neoplastic cells have a moderate amount of cytoplasm and formed vague acini.
Figure 9. Histopathology of the hepatic adenocarcinoma (40x)
Figure 10. Histopathology of the lung adenocarcinoma (2x)
Figure 11. Dermatohisto-pathology of alopecic skin (20x), showing follicular atrophy, parakeratosis and neutrophic epidermitis.
DISCUSSION
The pathophysiology of feline paraneoplastic alopecia is unknown. It is one of very few cutaneous paraneoplastic syndromes identified in veterinary medicine and is linked to pancreatic and biliary carcinoma.2-5 The first case series of 3 cats with this syndrome was published in 1994.2
A case report demonstrated that excision of the primary tumor was followed by resolution of dermatologic lesions, and subsequent metastatic disease mirrored a recurrence of dermatologic lesions.6 This particular case report demonstrated that, while pancreatic disease may be present and is likely the location of the primary tumor, metastatic hepatic lesions may be the most easily identifiable pathology antemortem. Therefore, it is important to determine if pancreatic pathology is also present.
Clinical Signs
Classic physical examination findings include shiny, nonpruritic symmetrical alopecia affecting the ventral body, face, and medial aspect of limbs, with easily epilated hair.6,10,11
- Less commonly, pinnal and periocular alopecia can occur.
- Abnormally soft footpads,6 dry footpad fissures,11 crusted footpads,12 and lightening of hair color10 have been reported as well.
- Pruritus has been linked to secondary Malassezia species infection in one report.6
- The most common sign of systemic illness is weight loss.3
Relation of Alopecia to Tumor
Feline paraneoplastic alopecia is characterized histopathologically by loss of the stratum corneum and severe follicular atrophy, with miniaturized hair bulbs.6,10,11 The shiny to glistening appearance of the skin is attributed to exfoliation of the stratum corneum,11 which may occur during normal or excessive grooming.
It is theorized that humoral factors are excreted or triggered by the tumor, but specific factors have not been identified. By definition, though, the dermatologic lesions are themselves noncancerous; they are, instead, neoplasm-related lesions that occur at a site distant from the primary tumor or its metastasis.3
Key Point: Application in Practice
The unique dermatologic signs associated with feline paraneoplastic alopecia—shiny, nonpruritic alopecia and easily epilated hair—should be a sentinel for possible intra-abdominal malignancy. Recognition of these signs may facilitate detection of pancreatic adenocarcinoma.
Therapy & Prognosis
Cats with pancreatic adenocarcinoma have a grave prognosis, and most have metastatic disease at the time of diagnosis.12 To the best of our knowledge, there are currently no effective treatments.
The Dermatology Component: Differential Diagnoses
Differential diagnoses for the alopecia are listed in Table 4.7,8 Rule outs were based upon:
- No evidence of skin fragility on physical examination, as reported in cats with hyperadrenocorticism9
- No ectoparasites identified on examination
- In this case, skin scraping, skin cytology, trichogram, and fungal cultures were not performed as the imaging and fine-needle aspiration biopsy results indicated a neoplastic process. No perifollicular inflammation or mites/fungal spores were seen in biopsy samples
- Normal total T4 level 3 weeks prior to referral (1.8 mcg/dL; reference interval, 0.8–4).
Telogen effluvium was possible as a consequence of internal or systemic disease as a synchronous trigger for the onset of telogen phase.8 However, the characteristic clinical appearance, absence of findings consistent with other disorders, and dermatohistopathology findings made paraneoplastic alopecia the most likely diagnosis in this case.
SUMMARY
Feline pancreatic adenocarcinoma is a rare condition; however, the uniqueness of dermatologic changes should be a sentinel for possible intra-abdominal neoplasia, typically pancreatic, and a trigger to pursue abdominal ultrasound and biopsy.
Jennifer C. Olson, DVM, practices at Alamo Feline Health Center in San Antonio, Texas. She received her DVM from Cornell University and completed an internship at VCA Alameda East Veterinary Hospital in Denver, Co.
Gary D. Norsworthy, DVM, Diplomate ABVP (Feline), is the owner of Alamo Feline Health Center in San Antonio, Texas, one of the largest feline practices in the United States. He is a frequent lecturer and the editor of the textbook, The Feline Patient. He received his DVM from Texas A&M University.
J. Scot Estep, DVM, Diplomate ACVP, is the owner of Texas Veterinary Pathology in San Antonio, Texas. He received his DVM from Oklahoma State University and completed a residency in pathology at the Armed Forces Institute of Pathology.
References
- Owen LN. TNM classification of tumors in domestic animals. Geneva: World Health Organization, 1980.
- Brooks DG, Campbell KL, Dennis JS, et al. Pancreatic paraneoplastic alopecia in three cats. JAAHA 1994; 30:557-563.
- Turek, MM. Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Derm 2003; 14: 279-296.
- Marconato L, Albanese F, Viacava P, et al. Paraneoplastic alopecia associated with hepatocellular carcinoma in a cat. Vet Derm 2007; 18:267-271.
- Van der Luer R, Van den Ingh T, Van Hoe N, et al. Feline paraneoplastic alopecia. Tijdschr Diergeneeskd 2008; 18(4):182-183.
- Godfrey DR. A case of feline paraneoplastic alopecia with secondary Malassezia-associated dermatitis. J Small Anim Pract 1998; 39:394-396.
- Scott DW, Miller WH, Griffin CE. Endocrine and metabolic diseases. In Scott DW (ed): Muller and Kirk’s Small Animal Dermatology, 5th ed. Philadelphia: WB Saunders, 1995, pp 704-710.
- Thoday KL. Diagnosis and management of symmetrical alopecia. In August JR (ed): Consultations in Feline Internal Medicine, 3rd ed. Philadelphia: WB Saunders, 1997, pp 231-245.
- Helton-Rhodes K, Wallace M, Baer K. Cutaneous manifestation of feline hyperadrenocorticism. In Ihrke PJ, Mason IS, White SD (eds): Advances in Veterinary Dermatology, Volume 2. Oxford: Pergamon Press, 1993, pp 391-396.
- Tasker S, Griffon DJ, Nuttall TJ, et al. Resolution of paraneoplastic alopecia following surgical removal of a pancreatic adenocarcinoma in a cat. J Small Anim Pract 1999; 40:16-19.
- Pascal-Tenorio A, Olivry T, Gross TL, et al. Paraneoplastic alopecia associated with internal malignancies in the cat. Vet Derm 1997; 8:47-52.
- Seaman RL. Exocrine pancreatic neoplasia in the cat: A case series. JAAHA 2004; 40:238-245.
Suggested Reading
Barrs VR, Martin P, France M, et al. What is your diagnosis? J Small Anim Pract 1999; 40:559.
Heripret D. Dermatological manifestations of systemic disease. In Guaguere E (ed): A Practical Guide to Feline Dermatology. Oxford: Blackwell Science, 2000, pp 14.1-14.10.
McLean DI, Haynes HA. Cutaneous manifestations of internal malignant disease: Cutaneous paraneoplastic syndromes. In Freedberg IM (ed): Fitzpatrick’s Dermatology in General Medicine, 6th ed. New York: McGraw-Hill, 2003, pp 1783-1796.