A divergent pseudoglandular configuration of cutaneous plasmacytoma in dogs

Abstract

Cutaneous and mucocutaneous plasmacytoma (PCT) is a common neoplasm of dogs. Tumors can be single or multiple and occur predominantly in the oral cavity, lip, ears, digits, and trunk. Although these tumors typically offer no diagnostic challenge for the pathologist, subsets of PCTs with atypical morphologic configurations may make differentiation from other neoplasms difficult. We describe 6 cases of canine cutaneous and mucocutaneous PCT with pseudoglandular arrangement of neoplastic cells. The mean age of affected dogs was 11.3 y, and multiple breeds and sites were affected. Histologically, neoplastic cells were arranged in sheets, packets, and pseudoglandular structures containing central accumulations of blood or eosinophilic material admixed with neoplastic cells and hemosiderin-laden macrophages. Given the presence of pseudoglandular structures resembling neoplastic acini, epithelial neoplasia was occasionally included in the differential diagnosis. Neoplastic cells were strongly immunopositive for multiple myeloma oncogene 1 (MUM-1) and immunonegative for pancytokeratin AE1/AE3. Canine cutaneous and mucocutaneous PCTs with pseudoglandular morphology may resemble epithelial neoplasia and raise questions about tumor histogenesis.

Cutaneous and mucocutaneous plasmacytoma (PCT) is a benign extramedullary plasma cell neoplasm that has been commonly reported in dogs and less commonly in cats and other species.^2,3,8 Canine PCT can affect individuals of various ages, and a clear breed or sex predilection has not been observed.^2,3,8 Tumors can be single or multiple and occur predominantly in the oral cavity, lip, ears, digits, and trunk, but other sites can also be affected.^2,7,8 PCTs typically do not offer a challenge for the pathologist, and the diagnosis can be made solely based on routine histopathology.^2,7,8 However, a subset of these tumors may have atypical morphologic features that may raise questions about tumor histogenesis. We describe herein 6 cases of canine cutaneous PCT with pseudoglandular arrangement of neoplastic cells resembling epithelial neoplasia.

Cases 1–5 were selected from the biopsy service at the University of Georgia Athens Veterinary Diagnostic Laboratory (AVDL; Athens, GA), and case 6 was selected from Antech Diagnostics (College Station, TX; dog 6). Submission forms, pathology reports, and slides were reviewed. Replicate tissue sections of all tumors were submitted to the AVDL routine diagnostic immunohistochemistry (IHC) service. IHC was performed on an automated stainer (Nemesis 3600, Biocare Medical, Concord, CA). A rabbit monoclonal antibody against multiple myeloma oncogene 1 (MUM-1; Biocare Medical) at a dilution of 1 in 50 for 60 min and a mouse monoclonal antibody against pancytokeratin AE1/AE3 (PCK; Cell Marque, Rocklin, CA) at a dilution of 1 in 100 for 90 min were used. For the MUM-1 IHC protocol, antigen retrieval on tissue sections was achieved using Reveal decloaker 10X (Biocare Medical) at a dilution of 1 in 10 for 15 min at 110°C. A biotinylated rabbit antibody (Vector Laboratories, Burlingame, CA) was utilized to detect the target, and the immunoreaction was visualized using 3,3-diaminobenzidine (DAB; Dako, Santa Clara, CA) substrate for 12 min counterstained with hematoxylin. For the PCK IHC protocol, antigen retrieval was achieved using Citra solution (BioGenex, Fremont, CA) at a dilution of 1 in 10 for 15 min at 110°C. A biotinylated mouse antibody (Vector Laboratories) was used to reveal the target, and the immunoreaction was visualized using DAB substrate for 12 min counterstained with hematoxylin. Control tissues were cutaneous PCT for MUM-1 and normal skin for PCK.

Case 1 was a 9-y-old spayed female Labrador Retriever with multiple hairless cutaneous nodules on the head, face, limbs, and trunk. Case 2 was a 15-y-old female Fox Terrier with a vulvar nodule. Case 3 was a 13-y-old neutered male Cocker Spaniel with a mass protruding from the right ear canal. Case 4 was a 14-y-old spayed female mixed-breed dog with a nodule on the third digit of the right pelvic limb. Case 5 was an 11-y-old neutered male Yorkshire Terrier with a nodule on the left carpus. Case 6 was a 6-y-old neutered male Yorkshire Terrier with an interdigital nodule on the left pelvic limb. All dogs recovered, and no recurrence was reported after surgical excision of the tumors.

Histologically, neoplastic cells were arranged in sheets, packets, and scattered pseudoglandular structures with central accumulations of blood or eosinophilic amorphous material admixed with neoplastic cells and hemosiderin-laden macrophages (Fig. 1). Because pseudoglandular structures resembled neoplastic acini, epithelial neoplasia was included in the differential diagnosis in cases 1 and 3 and, more specifically, as a possible metastatic thyroid tumor in case 3. Neoplastic cells in all cases were strongly immunopositive for MUM-1 (Fig. 1B, D) and immunonegative for PCK.

Figure 1.

Cutaneous plasmacytoma in dogs 2 (A) and 3 (C). Neoplastic plasma cells are arranged in a pseudoglandular configuration surrounding variable numbers of red blood cells. H&E. MUM-1 immunohistochemistry in dogs 2 (B) and 3 (D) reveals strong nuclear immunostaining diffusely throughout the tumor.

These 6 cases of canine cutaneous PCT had a distinct pseudoglandular configuration of neoplastic cells that resembled neoplastic acini and suggested epithelial neoplasia as a differential diagnosis. Diagnostic confirmation was achieved based on the strong immunoreactivity of neoplastic cells to MUM-1. MUM-1 IHC has been shown to have higher specificity and sensitivity in the diagnosis of cutaneous PCT in dogs compared to other plasma cell immunomarkers, such as CD79a and CD20. Thus, although MUM-1 can be also expressed by small subsets in canine B-cell lymphoma, MUM-1 IHC is highly reliable for diagnostic confirmation of canine cutaneous PCTs when used in conjunction with tumor morphology and/or other lymphocytic immunomarkers.⁹

Cutaneous and mucocutaneous PCTs are typically well-demarcated neoplasms composed of neoplastic plasma cells arranged in closely apposed sheets or cords supported by a fine fibrovascular stroma.^2,7,8 Similar to the cases of our report, human extramedullary PCT and myeloma may display many architectural variations, including nested and angiomatoid configurations that resemble neuroendocrine or vascular tumors, respectively.^1,4,5 Tumors with pseudofollicular or pseudoglandular configuration recapitulating thyroid follicles have also been described in humans.⁵ Other architectural features may include the presence of amyloid or mineral and bone differentiation, which can obscure neoplastic cells while maintaining their characteristic morphologic features.¹ Although there has been mention of canine PCTs forming closely packed nests or pseudoglandular structures in veterinary textbooks,³ detailed documentation of this feature is lacking in the veterinary medical literature. The majority of pseudoglandular arrangements in our case series surrounded red blood cells, but a few areas in which erythrocytes were tightly packed and indistinct from each other could be easily misinterpreted as proteinaceous fluid or colloid-like material. In fact, thyroid neoplasia was raised as a possibility in case 3, indicating that pathologists should be familiar with this pseudoglandular variant of PCTs in dogs. A morphologic classification of canine cutaneous and mucocutaneous PCTs has been reported and includes hyaline, mature, cleaved, asynchronous, and polymorphous types.⁷ However, no association has been found to date between tumor type and behavior, prognosis, or treatment.^2,6,7 All of the tumors in our study were classified as mature-type.^2,6,7