Lymphocytic mural folliculitis and pancreatic carcinoma in a cat

Abstract

A 9-year-old castrated domestic shorthair cat was presented with a 6 week history of progressive non-pruritic alopecia, polyphagia and weight loss. A diagnosis of lymphocytic mural folliculitis was made and the cat was treated with a combination of prednisolone and ciclosporin; this produced an improvement in the alopecia but no resolution. Sixteen months after the initial assessment and diagnosis, the cat was re-evaluated for intermittent vomiting and weight loss with normal appetite. On examination the dermatopathy was still evident and a mass involving the duodenum and pancreas was present, which was diagnosed as a pancreatic carcinoma. From this case it would appear that lymphocytic mural folliculitis might be an early dermatological manifestation of pancreatic neoplasia.

Case Report

Cutaneous paraneoplastic syndromes (PNSs) consist of dermatological signs associated with internal neoplasia, but which are not directly due to extension of the neoplasm to the skin. In addition, resolution of the cutaneous signs occurs after removal of the tumour. Although they are well recognised in humans, ¹ they are rarely reported in the dog and cat. Feline paraneoplastic alopecia (FPA) is a rare syndrome in which alopecia occurs in association with pancreatic or bile duct carcinoma. ² This report describes a case of FPA that was initially diagnosed as lymphocytic mural folliculitis 16 months prior to a diagnosis of pancreatic carcinoma.

A 9-year-old castrated male domestic shorthair cat was evaluated for progressive non-pruritic alopecia, polyphagia and weight loss. Appetite and activity were both normal and there was no excessive self-grooming. The alopecia was first noticed, approximately 6 weeks prior to assessment, on the lumbar spine, tail and ventral thorax with no response to ectoparasitic therapy. The alopecia subsequently progressed to the limbs and head. On physical examination the cat was thin, weighing 5 kg (down from 7 kg) and had bilaterally symmetrical alopecia on the ventral abdomen and patchy alopecia on the limbs, groin, perineal areas and head. The skin appeared thin and shiny, and the hair at the edge of the alopecic regions was easily epilated. The rest of the coat was poor and scaly. The only abnormalities on full blood count and serum biochemistry were thrombocytosis (752 × 10⁹ cells/l; reference interval 300–600 × 10⁹ cells/l) and hypoalbuminaemia (20 g/l; reference interval 25–30). Total T4 was within the reference interval, tests for feline leukaemia and feline immunodeficiency viruses were both negative, and routine urine and faecal analyses and abdominal ultrasonography showed no abnormalities. Histopathological examination of several 6 mm punch skin biopsies from the abdomen, lateral thorax and head revealed orthokeratotic hyperkeratosis with mild acanthosis of the underlying epidermis; dermal oedema with superficial perivascular infiltrates of mast cells, lymphocytes, plasma cells and rare eosinophils; multifocal perifollicular lymphocytic and histiocytic cell infiltrates, which invaded the outer sheath of hair follicles and extended into the follicular epithelium; and individual catagen arrest follicles. Both bacterial and fungal cultures from a skin biopsy showed no growth, and periodic acid-Schiff staining was negative for fungal elements. A diagnosis of lymphocytic mural folliculitis (LMF) was made. The cat was treated with a combination of prednisolone (5 mg once daily for 10 days followed by 2.5 mg once daily for a further 10 days, then 2.5 mg every second day) and ciclosporin (25 mg once daily for 30 days). Over the following 3 months there was a gradual improvement in the alopecia but without any resolution and no improvement in body weight. However, further weight loss was not reported. Over the following 12 months the condition of the cat remained static but never improved.

Sixteen months after the initial assessment and diagnosis of LMF, the cat was re-evaluated for progressive intermittent vomiting and weight loss. Appetite was still normal. On physical examination the cat had lost more weight (weight 3.7 kg), showed muscle atrophy, had bilaterally symmetrical alopecia on the ventral abdomen and thorax, and an irregular small cranial abdominal mass was detected on abdominal palpation. The skin was still thin and shiny. As before, the only abnormalities on full blood count and serum biochemistry were thrombocytosis (698 × 10⁹ cells/l; reference interval 300–600 × 10⁹/l) and hypoalbuminaemia (20 g/l; reference interval 25–30 g/l). Survey thoracic radiographs showed no abnormalities. An irregular, mottled, poorly vascularised echogenic mass (20 × 42 mm) in the region of the pancreas and duodenum and regional lymphadenomegaly was evident on abdominal ultrasonography. Fine-needle aspirate cytology of the abdominal mass revealed moderate numbers of anaplastic glandular cells with a minimal inflammatory response. On exploratory laparotomy, a large, firm mass involving the pancreas, duodenum and duodenal mesentery was identified and excised. Unfortunately, the cat died shortly after completion of the surgery. Sections from the excised mass revealed metastatic acinar cell pancreatic carcinoma. On skin biopsies taken at the time of surgery, LMF was still present.

PNSs are non-cancerous, neoplasm-related disorders that occur at a site distinct from the primary tumour or its metastases. They produce signs that reflect the remote effects of cancer rather than the direct effects caused by tumour growth or invasion. Presenting as endocrine, haematological, gastrointestinal, neurological, renal or cutaneous aberrations, PNSs may be the first sign of an underlying malignancy and may herald a certain tumour type. Their recognition, therefore, can be important to facilitate early diagnosis and treatment of the neoplasm. ³

FPA is a non-pruritic, progressive, symmetrical alopecia, which has been reported in association with either pancreatic or biliary carcinoma.^4–6 The reported median age of onset is 13 years, with no breed predilection. The chief presenting complaint is the dermatopathy, characterised by acute, progressive alopecia of 2 weeks to 10 months duration, with a median of 4 weeks. The dermatopathy in the cat in this report was subacute in onset, with duration of 16 months. Concurrent systemic signs associated with FPA include weight loss, variable degrees of inappetence, vomiting, diarrhoea and lethargy. Weight loss with polyphagia was evident in this cat. The hair loss is typically symmetrical and progresses from the ventrum to the head and to primarily the medial aspect of the extremities. Hair is easily epilated and alopecic skin is shiny, inelastic and thin, but not fragile. Although involvement of the footpad is reported to be common, it was not evident in this cat. Pruritus has been reported in FPA with secondary Malassezia species infections and flea infestations,^7,8 and it was suggested that the presence of yeast organisms in histopathological specimens from cats with generalised skin disease could serve as a harbinger of internal malignancy. ⁸

Lymphocytic mural folliculitis is a histopathological reaction pattern reported to occur in inflammatory skin disorders of the cat, especially allergic dermatoses such as atopic dermatitis, flea allergy and food allergy.^4,9 The condition has also been reported in several other dermatoses such as indolent ulcer, bacterial folliculitis and furunculosis, sterile panniculitis, systemic lupus erythematosus, eosinophilic granuloma, mosquito allergy, cryptococcosis, erythema multiforme, herpesvirus dermatitis, pemphigus foliaceus, pemphigus vulgaris, phaeohyphomycosis, solar dermatitis, toxic epidermal necrolysis, urticaria pigmentosa and xanthoma. ¹⁰ Infundibular lymphocytic interface or infiltrative mural folliculitis has been described in cats with thymic lymphoma. ¹¹

The typical histopathological changes in FPA skin are non-scarring alopecia, marked follicular telogenisation, miniaturisation and atrophy. Less specific findings include mild epidermal acanthosis and hyperplasia with thinning or absence of the stratum corneum and patchy parakeratosis with a mild, predominantly mononuclear, perivascular inflammatory infiltrate of the dermis.^5,6,12 The cat in this report showed a combination of FPA and LMF on dermal histopathology. Clinical differential diagnoses for FPA include hyperadrenocorticism, hyperthyroidism, dermatophytosis, demodicosis, self-induced alopecia, telogen defluxion, feline symmetrical alopecia and alopecia areata.^5,12 Specific features of the clinical presentation – as well as diagnostic tests, including adrenocorticotropic hormone stimulation and dexamethasone suppression tests, thyroid hormone measurement, Wood’s lamp examination, fungal culture, skin scraping, KOH preparation, faecal examination, trichograms and skin biopsy – are important to rule out these possibilities. Abdominal radiography and/or ultrasonography, as well as thoracic radiographs to evaluate for pulmonary metastasis, are important if FPA is suspected. Exploratory laparotomy with tissue biopsy is necessary to confirm the diagnosis of neoplasia. Other possible aetiologies for LMF were not specifically excluded at the time of the diagnosis of the pancreatic neoplasia, but were considered unlikely as the clinical presentation and signs had remained similar and, besides the reported changes, there were no overt changes present on survey radiographs, abdominal ultrasound, full blood count or serum biochemistry.

Neoplastic diseases of the exocrine pancreas and biliary tree are rare in the cat, with distant metastasis present in the majority of cases at presentation.^13,14 Twelve of the 14 cats reported in the literature died or were euthanased within 8 weeks of onset of clinical signs.^5,6,8 Skin lesions did not improve in any cat treated with corticosteroids; however, resolution of FPA was documented after surgical resection in a single case of solitary pancreatic tumour. ¹² Recrudescence of cutaneous lesions at the time of metastasis 18 weeks later in this case provides further evidence for the classification of FPA as a PNS.

In a retrospective study on feline pancreatic carcinoma, the most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea, ¹⁵ with an overall median survival time of 97 days; however, three of the cats survived over 1 year. That study concluded that feline pancreatic carcinoma is an aggressive tumour with a high metastatic rate and poor prognosis. However, the length of time cats show subclinical disease may vary and may extend to 16 months, as seen in this cat. A causal link between the skin lesions and the pancreatic carcinoma in this cat could not be categorically proven. It can be speculated that the mural folliculitis and the pancreatic carcinoma were occurring concurrently without any causal association, especially as mural folliculitis and interface dermatitis are both not specific for a PNS but rather a reaction pattern with a number of underlying causes. The durable and partial response to the therapy together with the static clinical signs of the dermatopathy at the time of diagnosis of the pancreatic carcinoma is unusual with such a paraneoplastic condition. However, the persistence of the cutaneous signs in this cat would suggest that the underlying aetiology was present over the duration of the cat’s illness and thus could also suggest an association between the cutaneous signs and the neoplasia.

Conclusions

This case provides possible evidence for a causal link between lymphocytic mural folliculitis and pancreatic neoplasia, which can be a form of FPA. Early investigation for pancreatic carcinoma in a cat with paraneoplastic alopecia or mural folliculitis may permit complete surgical removal of the neoplasia and thus improve the prognosis in such a patient.