Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

OBJECTIVES: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs). DESIGN: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. PROCEDURES: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. RESULTS: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. CONCLUSIONS: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs.

The industrial melanism mutation in British peppered moths is a transposable element.

Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution. The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria-typica polymorphism, and the gene it influences, are unknown. Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of 'jumping genes' as a source of major phenotypic novelty.

Melanosis Coli in Pigs Coincides With High Sulfate Content in Drinking Water.

Melanosis coli is a well-described condition in humans, characterized by the accumulation of lipofuscin-laden macrophages in the lamina propria of the colon, giving it a dark tone. An increased apoptosis rate of colonic epithelial cells appears to be the underlying pathogenesis. In pigs, oxidative damage has been proposed as one of the causes for melanosis coli. In this article, we report a series of cases of melanosis coli in pigs affecting several finishing units in the south of Spain. Large intestines had dark green to brown pigmentation of the mucosa. Histological, histochemical, and ultrastructural studies confirmed a high number of lipofuscin-laden macrophages in the lamina propria of the rectum and colon, which additionally stained positive for the apoptosis marker cleaved caspase-3. Of note, all affected finishing units utilized water supply with a high content of sulfates, which may be one of the causes for melanosis coli development in pigs.

Iris biopsy to investigate feline iris hyperpigmentation.

OBJECTIVE: To evaluate the benefit of iris biopsy in cats with iris hyperpigmentation to differentiate melanosis from early feline diffuse iris melanoma (FDIM). METHODS: The medical records of cats with unilateral iris hyperpigmentation that had undergone iris biopsy between February 2013 and September 2016 at Willows Veterinary Centre & Referral Service were reviewed. RESULTS: Seven cats with unilateral iris hyperpigmentation were included in this retrospective study. The biopsy procedure was performed under general anesthesia (n = 7) with neuromuscular blockade (n = 6) following pre-operative topical miotic therapy (n = 5). One to six biopsy samples per eye were harvested from areas of hyperpigmentation. The samples were partial thickness (n = 4 eyes) and full thickness (n = 3 eyes). Complications were minor: mild intra-operative hemorrhage (n = 4), fibrin clot (n = 2), corneal ulcer (n = 1), post-operative ocular hypertension (n = 1), dyscoria (n = 1), and pseudopolycoria (n = 2). The first biopsy was diagnostic in six cats; a repeat biopsy was necessary in one cat. Histopathology was consistent with melanosis in five cats and with early FDIM in two cats. Screening for signs of metastatic disease (thoracic computed tomography and abdominal ultrasonography) was negative in the two cats with a preliminary diagnosis of early FDIM. Subsequent enucleation and histopathology confirmed the initial diagnosis in both cases. CONCLUSIONS: Iris biopsy in cats with iris hyperpigmentation can be beneficial to differentiate melanosis from early FDIM and thereby help to justify the decision for early enucleation.

Physiological characterization of ocular melanosis-affected canine melanocytes.

OBJECTIVE: Cairn terriers with ocular melanosis (OM) accumulate large, heavily pigmented melanocytes in the anterior uvea. Darkly pigmented plaques develop within the sclera, leading us to hypothesize that OM uveal melanocytes may have an abnormal migratory capacity. ANIMALS STUDIED: Globes from OM-affected Cairn terriers and unaffected control eyes enucleated for reasons unrelated to this study were used for immunohistochemistry and to culture melanocytes for in vitro cell behavior assays. PROCEDURES: The scleral plaques of six dogs were immunolabeled for HMB-45, MelanA, PNL2, CD18, CD204, and Iba-1 and compared with the pigment cells accumulated within the irides. Cultured uveal melanocytes from OM-affected and control dogs were compared using conventional assays measuring cell proliferation, invasion capability, and melanin production. RESULTS: Melanocytes isolated from OM eyes had significantly elevated levels of per-cell melanin content and production compared to controls. The majority of pigmented cells in the scleral plaques were HMB45 positive indicating a melanocytic origin. Many were also CD18 positive. No differences were observed between cultured melanocytes from OM-affected and control uvea for standard in vitro proliferation or invasion assays. CONCLUSION: Pigmented cells which accumulate in the sclera of OM-affected Cairn terriers are predominantly melanocytes; however, in vitro assays of uveal melanocytes did not reveal differences in migratory behavior between OM and control cells. Migratory behavior of OM-melanocytes may be environment-dependent. We suggest that RNA sequencing and differential expression analysis would be a useful next step in understanding this disease.

Potential Causative Mutation for Melanism in Rats Identified in the Agouti Signaling Protein Gene (Asip) of the Rattus rattus Species Complex on Okinawa Island, Japan.

The occurrence of black fur, or melanism, in many mammalian species is known to be linked to DNA sequence variation in the agouti signaling protein (Asip) gene, which is a major determinant of eumelanin and pheomelanin pigments in coat color. We investigated 38 agouti (i.e., banded wildtype) and four melanistic Rattus rattus species complex (RrC) lineage II specimens from Okinawa Island, Ryukyu Islands, Japan, for genetic variation in three exons and associated flanking regions in the Asip gene. On Okinawa, a predicted loss-of-function mutation caused by a cysteine to serine amino acid change at p.124C>S (c.370T>A) in the highly conserved functional domain of Asip was found in melanistic rats, but was absent in agouti specimens, suggesting that the p.124C>S mutation is responsible for the observed melanism. Phylogeographic analysis found that Asip sequences from Okinawan RrC lineage II, including both agouti and melanistic specimens, differed from: 1) both agouti and melanistic RrC lineage I from Otaru, Hokkaido, Japan, and 2) agouti RrC lineages I and II from South Australia. This suggests the possibility of in-situ mutation of the Asip gene, either within the RrC lineage II population on Okinawa or in an unsampled RrC lineage II population with biogeographic links to Okinawa, although incomplete lineage sorting could not be ruled out.

Primary intranasal melanoma with brain invasion in a dog.

A 6-year-old castrated male boxer dog with right-sided dark purulent nasal discharge and acute bilateral blindness was diagnosed on magnetic resonance imaging (MRI) and then on necropsy with primary nasal malignant melanoma that extended into the brain, as well as concurrent ocular melanosis. There was no evidence of metastasis in other organs.

Un cas de mélanome primitif des fosses nasales avec invasion cérébrale chez un chien. Un boxer mâle castré de 6 ans a été présenté pour écoulement nasal purulent et de couleur foncée à droite et perte de vision bilatérale aiguë. Un mélanome malin nasal primaire qui s'étendait dans le cerveau, ainsi qu'une mélanose oculaire, ont été diagnostiqués par imagerie à résonnance magnétique (IRM) puis nécropsie. Il n'y avait pas d'évidence de métastases dans les autres organes.(Traduit par les auteurs).

Evidence of Oxidative Injury in Pigs With Melanosis Coli.

Melanosis coli is a dark discoloration of the colon due to accumulation of pigment-laden macrophages in the lamina propria. Three case submissions were received where rectal discoloration was reported at slaughter in pigs from separate production systems and melanosis coli was confirmed microscopically. Tissues from affected and unaffected cohort pigs were evaluated for evidence of oxidative damage using immunohistochemical staining for 3-nitrotyrosine, 4-hyroxynonenol, and malondialdehyde. Affected colons had significantly greater immunolabeling for all 3 target compounds than unaffected colons (P ≤ .001, all analyses). Hepatic vitamin E levels were low in both affected and unaffected pigs, and there was a trend toward lower values in affected pigs. Given the limited number of slaughter-collected samples available for this investigation, further study is warranted to elucidate the possible association between low vitamin E concentrations and oxidative damage in cases of melanosis coli in pigs.

Exclusion of eleven candidate genes for ocular melanosis in Cairn terriers.

BACKGROUND: Ocular melanosis of Cairn terrier dogs is an inherited defect characterized by progressive pigmentation of both eyes which can result in glaucoma and blindness. Pedigree analysis suggests the trait has an autosomal dominant mode of inheritance. We selected 11 potential candidate genes and used an exclusion analysis approach to investigate the likelihood that one of the candidate gene loci contained the Cairn terrier-ocular melanosis locus. RESULTS: Two polymorphic loci were identified within or close to each candidate gene. Genotyping of at least 10 ocular melanosis Cairn terriers for each marker showed that there was no single shared allele for either of the two polymorphic markers identified in ASIP, COMT, GPNMB, GSK3B, LYST, MC1R, MITF, SILV, TYR, TYRP1,and TYRP2. This is strong evidence to exclude each locus as the site of the ocular melanosis mutation (probability of a false exclusion calculated for each gene ranged from 1.59 × 10-4 to 1 × 10-9). CONCLUSIONS: None of the 11 potential candidate genes selected are likely to be the gene locus for ocular melanosis in Cairn terriers.

An unusual case of ocular melanosis and limbal melanocytoma with benign intraorbital extension in a dog.

This case report describes concurrent ocular melanosis and limbal melanocytoma in a 6-year-old Golden Retriever dog. Three years prior, the pet was examined for progressive corneal pigmentation and started on topical Tacrolimus but was subsequently lost to followup. Current ophthalmic examination revealed a large pigmented limbal mass and severe corneal pigmentation of the left eye as well as a small focal raised pigmented mass of the right third eyelid. Due to extent and rapidity of tumor growth, the left eye was removed via transconjunctival enucleation and submitted for histopathologic examination. At the time of surgery, numerous orbital structures including intraorbital fat, extraocular muscles, and portions of the proximal nasolacrimal drainage apparatus contained multifocal areas of black pigmentation. These tissues were subsequently removed and submitted for microscopic analysis. The pigmented mass of the right third eyelid was also excised. Histopathology of the left eye and orbital contents revealed a limbal melanocytoma extending to the bulbar conjunctiva and orbital space forming a large, markedly necrotic mass. Diffuse, severe ocular melanosis, abnormal stromal pigmentation of the sclera and orbital tissues, and corneal stromal pigmentation were noted. The mass of the right third eyelid was confirmed to be a conjunctival melanocytoma. To the authors' knowledge, this is the first report of concurrent ocular melanosis and limbal melanocytoma with orbital infiltration. The peculiar multifocal distribution of melanocytes throughout ocular connective tissues may explain the development of multiple melanocytic lesions in this patient.

Two different procedures for managing ocular melanosis presenting scleral pigmentation with glaucoma in a Shih-Tzu dog: A case of definitive diagnosis in one eye and a presumed diagnosis in the contralateral eye.

A 12-year-old castrated male Shih-Tzu dog was referred for uncontrolled glaucoma and uveitis with highly pigmented sclera, in both eyes (OU). On ophthalmic examination, the menace response, dazzle reflex and pupillary light reflex were negative OU. The intraocular pressure was 27 mmHg in the right eye (OD) and 70 mmHg in the left eye (OS) despite the administration of antiglaucoma eyedrops. Ultrasound biomicroscopy revealed a closed ciliary cleft OU. Ocular ultrasonography revealed hyperechoic materials in the vitreous OU and retinal detachment OS. When presented for recheck, an extensive malacic corneal ulcer was observed OS. To relieve pain in the blind eyes, enucleation OS and pharmacologic ciliary body ablation (CBA) OD were performed. Histologically, ocular melanosis, which is an inherited disease in the Cairn Terrier breed, was identified in the enucleated eye. The uvea was heavily pigmented. The iris and ciliary body were mildly distorted by a single population of large, round, nonneoplastic cells with pigmented cytoplasm. There was no evidence of an intraocular mass or metastasis before and after intravitreal CBA. This is the first report of bilateral ocular melanosis in a Shih-Tzu dog. Ocular melanosis is a possible differential diagnosis for globe presenting scleral pigmentation with glaucoma in even non-Cairn Terrier breeds and pharmacologic CBA could be considered as a treatment for ocular melanosis with end-stage glaucoma.

The pathologic features of neurocutaneous melanosis in a cynomolgus macaque.

Neurocutaneous melanosis (NCM) is a rare phakomatosis characterized by proliferation of melanin-producing cells in both the skin and the brain. In this study, we describe the clinical and pathologic features of NCM in a 4.5-year-old female cynomolgus macaque. Histopathologically, skin lesions showed foci of nests and cords of pigmented cells in the dermis similar to blue nevi in humans. In the brain, focal pigmented cell infiltration was observed in the connective tissue under the leptomeninges and in the brain parenchyma. The pigmented cell was moderately reactive with a pan-melanoma antibody (melanoma(pan)) in the skin. In the brain, the pigmented cell was moderately to strongly positive for melanoma(pan) in subleptomeningeal areas and in the cerebral cortex. Melanosomes were observed in pigmented cells in the brain by electron microscopic examination. Based on the histologic, immunohistochemical, and electron microscopic results, the diagnosis of NCM was made. This case is possibly the first report of the condition in animals.

[Melanosis of adipose tissue in a 17-month-old German Fleckvieh bull (Bos taurus)]. / Melanose von Fettgewebe bei einem 17 Monate alten Stier der Rasse Deutsches Fleckvieh (Bos taurus).

At meat inspection of a 17-month-old bull (German Fleckvieh), patchy dark discoloration of various organs and tissue sites was noted that was most prominent in perirenal adipose tissue. Microscopic analysis revealed melanosis, that is a congenital melanocytic dystopia, as the underlying cause. To the best of our knowledge, this is the first case of melanosis detected in adipose tissue in cattle. We speculate that there is a possible pathogenetic link between obesity and melanosis in the animal.

Ocular melanosis in the Cairn Terrier: histopathological description of the condition, and immunohistological and ultrastructural characterization of the characteristic pigment-laden cells.

OBJECTIVE: To describe the microscopic features and lineage of proliferating/infiltrating pigmented cells in ocular melanosis of Cairn Terriers. Animals studied Forty-nine globes removed from 45 Cairn Terriers with ocular melanosis and three globes from control dogs were available for microscopic examination. PROCEDURES: All globes were examined histologically, eight affected and three control globes were also examined by immunohistochemistry, and three affected and three control globes by transmission electron microscopy. RESULTS: Large round pigment-laden cells infiltrated the anterior uvea, obscured the drainage angle and were present within the sclera and episclera of affected globes. Similar pigmented cells were present in lower numbers in the posterior segment of the globe, the optic nerve meninges and periphery of the optic nerve. Changes due to chronic glaucoma were present in many globes and some had evidence of uveitis. Many of the pigmented cells were immunoreactive to HMB45 and some were MITF and vimentin positive. One globe, which was inflamed when removed, had many pigmented cells that were CD18 immunoreactive. The other eyes had lower numbers of CD18 positive cells. The pigmented cells were not immunoreactive to smooth muscle actin, S-100, MART/Melan A, chromogranin A/B, PGP 9.5, synaptophysin, MNF116, AE1/AE3, and CD45. Ultrastructurally many of the pigmented cells had features typical of melanocytes while a smaller number appeared to be melanophages. CONCLUSIONS: Ocular melanosis in Cairn Terriers is characterized by an infiltration of pigment-laden cells predominantly, but not exclusively, within the anterior uvea and anterior sclera. Most of these cells appear to be melanocytes although a variable proportion are pigment-laden melanophages.

Primary Meningeal Rhabdomyosarcoma of the Spinal Cord of a Young Dog with Neuromelanocytosis and Multiple Cutaneous Neurofibromas.

A 7-week-old male black Labrador retriever puppy was presented for post-mortem examination following progressive hindlimb paralysis and multiple masses within the skin. A highly compressive and infiltrative intradural mass was found within the T9-T11 spinal cord. Microscopical and immunohistochemical analysis revealed features compatible with spindle cell rhabdomyosarcoma (RMS). The adjacent spinal cord had numerous melanin-containing cells, arranged in small nodules, predominantly within the grey matter (proposed term of 'micronodular neuromelanocytosis') and the left lateral thorax had multifocal dermal neurofibromas. In this case, the constellation of proliferative/neoplastic lesions represents a unique case presentation with unclear aetiology. Primary canine meningeal RMS of the spinal cord has not been reported previously and represents a novel differential diagnosis for spinal tumours of young dogs. Moreover, such cases should be assessed for the presence of additional congenital abnormalities.

Skin and abdominal fascia melanization in broiler chickens.

Increased trimming and consequent carcass downgrade was experienced in a broiler flock. Condemned birds had gray to black pigmentation of the subcutaneous tissue and fat of the abdomen, and bluish pigmentation of the shanks. Histopathology revealed accumulation of melanin in these tissues. No significant bacteria were isolated. Accumulation of melanin in the skin and fascia is because of the cumulative and interactive effects of several genes. Additionally, pigmentation of abdominal fat has a high correlation with accumulation of melanin in the skin of the shanks. Although melanization of the skin and abdominal fascia is not harmful to people, it may cause severe economic losses to the producer.

Nasal melanosis in three dogs.

Cytologically and histologically confirmed nasal melanosis was detected by rostrocaudal rhinoscopic evaluation of three dogs with unilateral nasal discharge caused by a chronic and severe odontopathic rhinitis. The extraction of affected teeth and prolonged antibiotic therapy led to a complete resolution of nasal disease. The nasal melanosis could be considered a partial metaplastic transformation of mucosal respiratory cells with accumulation of intracytoplasmic melanin.

Role of sulfites and 4-hexylresorcinol in microbial growth and melanosis prevention of deepwater pink shrimp (Parapenaeus longirostris) using a controlled atmosphere.

A controlled atmosphere containing 48% CO2 and 7% O2 was used in association with refrigeration for storage of deepwater pink shrimp (Parapenaeus longirostris). Shrimp were treated with two different concentrations of sodium metabisulfite or 4-hexylresorcinol and subjected to the controlled atmosphere immediately after capture onboard ship or on arrival in port. Total volatile basic nitrogen, total viable counts, enterobacteria, lactic acid bacteria, and luminescent bacteria were determined, and black spot progression was evaluated. The combined effect of controlled atmosphere and melanosis inhibitors was used to delay black spot development as compared to the shrimp stored in ice alone. Storage under the controlled atmosphere without ice limited microbiological quality, namely, total viable counts, but enterobacterial growth was lower.

Pilar neurocristic hamartoma: its relationship to blue nevus and equine melanotic disease.

A unique pigmented lesion, judged to be a hamartoma of neural crest origin, occurring in a female patient, is compared with equine melanotic disease, The characteristic perifollicular arrangement of pigment-laden spindle cells is remarkably similar in both. Previously described patch- and plaque-like blue nevi in humans are also closely related. Light and ultrastructural features showed differentiation toward both nevus cells and Schwann cells, and it is proposed that the lesion be termed pilar neurocristic hamartoma.

Melanotic hamartoma of the hind brain in a riding horse.

A 3 1/2-year-old bay gelding of the cob type showed nervous signs and coughing associated with breaking-in and exercise. At post-mortem examination, heavy melanin pigmentation of the meninges of the hind brain and the medulla was identified and, on histological examination, melanin-containing cells were found within connective tissue extending into the medulla. The lesion was considered to be a melanotic hamartoma.