Ilene B. Bayer-Garner

Immunohistochemical staining for androgen receptors: a sensitive marker of sebaceous differentiation.

Androgen receptors (AR) are present in normal skin being localized to the basal and differentiating cells of the sebaceous gland, and as such, sebaceous glands are androgen sensitive tissue. Androgen receptor expression was examined in 43 sebaceous neoplasms including 8 sebaceous carcinomas, 22 sebaceous adenomas, 12 specimens showing sebaceous hyperplasia, and 1 sebaceous epithelioma, as well as in 14 squamous cell carcinomas, 2 clear cell acanthomas, and 35 basal cell carcinomas. Epithelial membrane antigen (EMA) expression was also examined in all of the sebaceous neoplasms. All specimens were fixed in formalin and embedded in paraffin. Diffuse positive nuclear androgen receptor antibody immunohistochemical staining was observed in all samples of sebaceous neoplasms, whereas approximately 60% of basal cell carcinomas showed only focal positivity for nuclear androgen receptor immunoreactivity. Clear cell acanthomas and squamous cell carcinomas were uniformly negative. Whereas all sebaceous neoplasms exhibited immunoreactivity for androgen receptors, the staining pattern was more marked in the nuclei of seboblasts and differentiating sebocytes in the adenomatous, hyperplastic, and epitheliomatous lesions than in the nuclei of the less differentiated sebaceous carcinoma cells. All the sebaceous neoplasms except for sebaceous carcinomas exhibited immunoreactivity for EMA. In the sebaceous carcinomas, EMA staining was absent in the most poorly differentiated specimen, but with increasing differentiation, the carcinomas became immunoreactive to EMA. We have shown that the nuclei of sebaceous neoplasms, including sebaceous gland carcinomas, show immunoreactivity for androgen receptors (AR), that immunohistochemical staining for the presence of AR may be a reliable marker of sebaceous differentiation, and that the AR may be a better marker of sebaceous differentiation than EMA, particularly in poorly differentiated sebaceous carcinomas.

Syndecan-1 (CD138) Immunoreactivity in Bone Marrow Biopsies of Multiple Myeloma: Shed Syndecan-1 Accumulates in Fibrotic Regions

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma proliferation and dissemination. Flow cytometry analysis of myeloma cells in bone marrow specimens shows heterogeneity in cell surface syndecan-1 expression. It is not known whether weaker expression correlates with more aggressive disease. However, recent reports suggest that variations in syndecan-1 staining intensity on myeloma cells may be an artifact of specimen handling. In this study, we evaluate syndecan-1 expression in bone marrow biopsy sections from 28 multiple myeloma patients, to elucidate the heterogeneity of syndecan-1 expression in situ. Immunoreactivity for syndecan-1, using the antibody B-B4 (CD138), was found in more than 95% of multiple myeloma cells in 27 of 28 biopsies. However, one biopsy had more than 50% CD138-negative cells and cells with weak CD138 expression were identified in the majority of cases. Loss of syndecan-1 did not appear to relate to myeloma cell differentiation. In addition, syndecan-1 was detected on intravascular and intrasinusoidal myeloma cells suggesting that loss of syndecan-1 may not be required for extramedullary dissemination. Bone marrow biopsies from nine additional patients, with variable CD138 staining intensity on myeloma cells as determined by flow cytometry, were studied by immunohistochemistry. The heterogenous CD138 expression was confirmed in situ, with weakly positive cells concentrated in areas of reticulin fibrosis. These cells had a disrupted pattern of membrane staining in contrast to the strong linear membrane staining seen in the other multiple myeloma cells. In addition, the fibrotic stroma stained intensely for syndecan-1. Accumulation of syndecan-1 within the extracellular matrix of the marrow likely is derived by shedding of the molecule from the surface of myeloma cells. Because syndecan-1 can act to regulate the activity of heparan-binding growth factors, these reservoirs of syndecan-1 may play a critical role in promoting myeloma pathogenesis, or in regeneration of the tumor after chemotherapy.

Plasma Cells in Chronic Endometritis are Easily Identified When Stained with Syndecan-1

Background: Chronic endometritis has been observed in 3–10% of women with irregular uterine bleeding who undergo endometrial biopsy. The diagnosis of chronic endometritis rests on the recognition of plasma cells in endometrial tissue that may show a prominent spindle cell stromal component, and is frequently difficult to date. Syndecan-1 is a cell-surface proteoglycan that is expressed on the cell surface of plasma cells. Design: Eighteen endometrial curettage cases with the diagnosis of chronic endometritis and 25 endometrial curettage cases of dysfunctional uterine bleeding, in females under the age of thirty-five in whom no other histopathologic changes were noted, were reviewed for the presence of plasma cells. Sections were then stained with syndecan-1. Results: All of the chronic endometritis cases showed easily visible syndecan-1 staining of plasma cell membranes. None of the cases of dysfunctional uterine bleeding showed presence of plasma cells in either the hematoxylin and eosin stained or syndecan-1 stained sections. Conclusions: In cases of suspected chronic endometritis in which no plasma cells can be found on hematoxylin and eosin stained slides, syndecan-1 may be an effective adjunct in the identification of plasma cells and thus aid in the diagnosis of chronic endometritis.

The expression of syndecan-1 is preferentially reduced compared with that of E-cadherin in acantholytic squamous cell carcinoma.

Background: Syndecan‐1 and E‐cadherin are cell adhesion molecules which are expressed primarily on the surface of adult epithelial cells. They appear to be co‐regulated and may act in concert to stabilize the epithelium. Loss of expression of both E‐cadherin and syndecan‐1 is seen in malignant transformation and invasion.

Syndecan-1 expression is decreased with increasing aggressiveness of basal cell carcinoma

Syndecans, a family of cell-surface proteoglycans of which syndecan-1 is the prototypical member, play an important role in limiting tumor growth and invasive capacity through their actions as receptors for growth factors and extracellular matrix. Cutaneous biopsy specimens of basal cell carcinoma, including superficial, nodular, infiltrative, and morpheic subtypes, were assessed regarding the pattern of syndecan-1 expression. We found that with increasing aggressiveness of basal cell carcinomas, syndecan-1 expression is lost from the surface of the neoplastic cells. However, within the dermis, which is normally devoid of syndecan-1 expression, immunopositivity for syndecan-1 is present in areas adjacent to aggressive tumors. This pattern of staining indicates that syndecan-1 expression is produced by stromal cells rather than being shed by the carcinoma cells into the stroma.

Routine Syndecan-1 Immunohistochemistry Aids in the Diagnosis of Chronic Endometritis

CONTEXT Chronic endometritis is reportedly observed in 3% to 10% of women undergoing endometrial biopsy for abnormal uterine bleeding. The diagnosis of chronic endometritis rests on the identification of the plasma cells. Their identification may be obscured by a mononuclear cell infiltrate, plasmacytoid stromal cells, abundant stromal mitoses, a pronounced predecidual reaction in late secretory endometrium, menstrual features, or secondary changes due to exogenous progesterone treatment prior to the biopsy. Syndecan-1 is a proteoglycan that is found on the cell surface of plasma cells and keratinocytes. Immunohistochemistry stains for this antibody may facilitate diagnosis of chronic endometritis. OBJECTIVE To determine whether or not routine syndecan-1 immunohistochemistry will aid in the diagnosis of chronic endometritis. DESIGN Immunohistochemistry stains for syndecan-1 were performed on 3 levels of 47 endometrial biopsies from patients with abnormal uterine bleeding. None of the patients had endometrial hyperplasia or an underlying malignancy. Clinical correlation and follow-up was attempted in 20 cases that showed evidence of plasma cells by syndecan-1 by immunohistochemistry. RESULTS Plasma cells were identified in 20 cases, 7 of which were initially diagnosed as chronic endometritis. The remaining 13 positive cases were diagnosed as tubal metaplasia (1), secretory endometrium (4), proliferative endometrium (4), menstrual endometrium (1), endometrial polyp (1), secretory endometrium with endometrial polyp (1), and endometrial polyp with exogenous hormone effect (1) based on the original hematoxylin-eosin section. CONCLUSIONS Syndecan-1 may be a useful adjunct in the diagnosis of chronic endometritis. Approximately half of the cases of chronic endometritis responded to an antibiotic regime; thus, this diagnosis is important and may potentially obviate the need for surgical intervention.

Monkeypox virus: histologic, immunohistochemical and electron-microscopic findings

Background:  Human monkeypox, an emerging viral zoonosis first recognized in Africa, has recently emerged in the mid‐western US. Initially, it presents with skin eruptions and fevers with diaphoresis and rigors. Clinically, the skin lesions progress from papules to vesiculopustules to resolving eschars.

Syndecan-1 is strongly expressed in the anagen hair follicle outer root sheath and in the dermal papilla but expression diminishes with involution of the hair follicle.

Syndecan-1 is the prototypic member of a family of heparan sulfate–bearing cell surface proteoglycans that function in adhesion, cell–extracellular matrix interactions, migration, and proliferation. During embryogenesis, syndecan-1 expression in the epithelium is downregulated when the epithelium gives rise to motile mesenchymal cells, whereas mesenchymal syndecan-1 expression is upregulated during organ formation. In aggressive basal cell carcinomas, syndecan-1 expression is evident in the stroma. Some neoplastic cells induce stroma to meet needs for growth, and it may be the mesenchymal cells that produce and shed syndecan-1 into the stroma. The physiologic mechanism by which the hair follicle undergoes its cyclic process of involution and formation of a new active hair follicle is not well understood. Sixty scalp biopsies and a large scalp resection were evaluated for syndecan-1 expression within hair follicles in the growing (anagen), involuting (catagen), and resting (telogen) phases. Strong syndecan-1 immunoreactivity was evident in the outer root sheath (ORS) of the anagen hair follicle, but this expression diminished in intensity with the involution and resting stages in the hair follicle cycle. The diminution of syndecan-1 immunoreactivity in the ORS of involuting and resting hair follicles may be a result of terminal keratinocyte differentiation. Syndecan-1 was also present in the dermal papilla of the anagen hair follicle, where it may promote growth factor–mediated cell signaling that induces and maintains growth of the hair shaft and the inner root sheath.

Epithelial sheath neuroma: a case report and discussion of the literature.

Here, a case of a rare epithelial sheath neuroma (ESN) is reported. A 49-year-old white female presented with a 5 mm solitary, slightly raised, erythematous, itchy papule on her right upper back. The clinical impression was consistent with an inflamed nevus. The patient had no past medical history of malignancy or a family history of neurofibromatosis. There was no prior trauma, surgical procedures, or skin disease at the site. After excision, the patient has had no recurrence at the surgery site during a 4-months follow-up period. ESN is characterized by enlarged nerve fibers ensheathed by a sometimes keratinized squamous epithelium located in the superficial dermis where large nerves are not normally found. It is believed to be a benign neoplasm and simple excision is curative. The histologic differential diagnosis of ESN is presented, and possible mechanisms of its pathogenesis are discussed. It is important for the pathologist and dermatologist to be cognizant of this lesion to prevent misdiagnosis of perineural invasion.

CD117, but Not Lysozyme, Is Positive in Cutaneous Plasmacytoma

CONTEXT CD117 (c-Kit) and lysozyme are frequently expressed by myeloblasts and are sensitive markers for the diagnosis of extramedullary myeloid tumor. The diagnosis of cutaneous plasmacytoma presents a degree of difficulty, particularly with the plasmablastic variant, which can mimic hematologic as well as epithelioid malignancies. Approximately 25% of multiple myelomas express CD117 in the bone marrow by flow cytometry. Lysozyme immunoreactivity has been previously shown in 30% of poorly differentiated myelomas, while it is nonreactive in nonmalignant plasma cells. OBJECTIVE To ascertain whether CD117 and lysozyme can aid in the diagnosis of cutaneous plasmacytomas, particularly the plasmablastic type. DESIGN Pathology reports of 2357 patients with a diagnosis of multiple myeloma were reviewed to find 13 cutaneous plasmacytomas (8 Bartl grade II, 5 Bartl grade III). Formalin-fixed, paraffin-embedded tissue sections were stained with CD117 and lysozyme on the Dako Autostainer system.Setting.-Patients with the diagnosis of multiple myeloma who developed cutaneous plasmacytoma(s). RESULTS The cutaneous plasmacytomas uniformly expressed CD117 in a cytoplasmic or membranous and cytoplasmic distribution with varying degrees of staining intensity unrelated to the Bartl grade of the lesion, while they were uniformly negative for lysozyme. CONCLUSIONS CD117 is a sensitive marker for malignant plasma cells in paraffin-embedded tissue, while lysozyme does not help identify poorly differentiated malignant plasma cells. While CD117 alone does not distinguish extramedullary myeloid tumor from poorly differentiated myeloma, the combination of CD117 and lysozyme may allow their differentiation. The possibility of c-kit inhibitors being used in the treatment of other hematopoietic malignancies allows speculation regarding implications for the treatment of multiple myeloma.