Folliculotropic mycosis fungoides associated with follicular mucinosis: A case report and mini review.

Key Clinical Message: F-MF is a rare non-classic variant of MF. In the case of hair loss, this should be a diagnostic consideration. The essence of the diagnosis of F-MF is a careful medical history, physical examination, and a combination of immunohistological and molecular analyses (Cureus. 2022; 14:e21231, Ann Saudi Med. 2012; 32:283, Oman Med J. 2012; 27:134, Int J Dermatol. 2016; 55:1396, Saudi Med J. 2018; 39:994 and Case Rep Oncol. 2018; 11:436). Abstract: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with multiple subtypes. Follicular MF (F-MF) is a non-classic variant of MF. Histological features entail folliculotropism and damage of the epithelium lining of the hair follicles with or without mucin deposition. A 52-year-old male patient complained of recurrent skin lesions on the scalp over 8 months. The lesions appeared suddenly, enlarged over time, and became itchy. A skin punch biopsy was performed. Histological features included mucin deposits in the epithelium of the hair follicles and dense, predominantly perifollicular atypical lymphocytes infiltrating the follicular epithelium. The lymphoid cells were composed of CD3-positive T cells (CD4/CD8-positive T cells) with a shift in favor of the former. The case was diagnosed as F-MF on an immunohistological basis. The diagnosis of F-MF is often difficult for dermatologists and dermatopathologists alike. Not only clinicopathological correlations but also immunohistochemical and molecular analysis are required.

Alterations of COX-2, HER-2/neu and E-Cadherin protein expression in the prostatic adenocarcinoma: preliminary findings.

Altered expression of the pro-inflammatory enzyme cyclooxygenase (COX)-2, E-Cadherin cell-cell adhesion protein and Human epidermal growth factor receptor 2 (HER-2/neu, a proto-oncogene) are involved in the pathogenesis of several cancers including the prostatic adenocarcinoma (PRCa). However, to date the results of the previous studies in this neoplasm are controversial, and the relationships among expression of these molecules in benign prostatic hyperplasia (BPH) and PRCa are mostly unknown. We hypothesize that "there are alterations of COX-2, HER-2/neu and E-Cadherin protein expression in PRCa". We carried out this study to test our hypothesis and to assess the relationships among these molecules both in PRCa and BPH. We used immunohistochemistry to evaluate the expression of these proteins in the tissue specimens of both BPH (27 cases) and PRCa (45 cases). Immunohistochemical staining patterns verified over-expression of COX-2 and HER-2/neu proteins in PRCa as compared to BPH. Alternatively, there was an aberrant (reduced) E-Cadherin protein expression in PRCa. There were weak positive correlations between COX-2 versus HER-2/neu expression. A weak negative correlation was noted between COX-2 and E-Cadherin expression. In conclusion, there were alterations of COX-2, HER-2/neu and E-Cadherin proteins in PRCa. The molecular alterations of the relevant genes and the therapeutic ramifications (the development of selective inhibitors to COX-2 and HER-2/neu) of these preliminary findings are open to further investigations.

Steroid therapy is associated with decreased numbers of dendritic cells and fibroblasts, and increased numbers of satellite cells, in the dystrophic skeletal muscle.

BACKGROUND: The possible therapeutic benefits of using steroids to enhance muscle strength and slow disease progression in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) has been examined previously. In this investigation, it was hypothesised that steroid therapy is associated with morphological changes in the dystrophic muscle. OBJECTIVES AND METHODS: To test this hypothesis, two muscle biopsies were obtained (one biopsy before treatment, and the second 6 months following prednisone therapy) from 24 patients with dystrophies (18 DMD, 6 BMD). The participants were categorised into: control (6 specimens, normal muscle), untreated and treated groups. The muscle was evaluated for ultrastructural changes using transmission electron microscopy (TEM). RESULTS: In the untreated group, the muscle fibres were degenerated and of variable sizes. The myofibrils were thin with either complete loss of bands and/or abnormal banding patterns. The Z-lines were irregularly spaced and loosely registered. The mitochondria of the myofibrils were small, few, spherical and irregularly distributed. Numerous dendritic cells (DCs) with euchromatic nuclei, and multiple and long dendrites, were seen among the myofibrils. The collagen fibres among the muscle fibres (endomysium) were numerous and large. The satellite cells had euchromatic nuclei with clumps of heterochromatin. In the treated group, the muscle fibres had a relatively uniform size with occasional fibres showing partial degeneration. The myofibrils had a relatively similar diameter comparable to that of normal muscle .The degenerated areas were small in size with occasional foci showing loss of banding pattern, and abnormal short bands with thick and hazy Z-lines. The mitochondria of the myofibrils were numerous, spherical, small in size and regularly arranged between the myofibrils. Few DCs, with heterochromatic nuclei, and few and short dendrites appeared between the myofibrils. The collagen fibres between the muscle fibres (endomysium) were numerous and large. As compared with the treated group, there was a statistically significant increase (p<0.05) in the numbers of DCs (0.7+/-0.2 vs 1.6+/-0.3) and fibroblasts (1.9+/-0.2 vs 2.9 +/-0.3) in the untreated group. Alternatively, there was a statistically significant decrease (p<0.05) in the numbers of satellite cells (1.2+/-0.2 vs 0.6+/-0.1). CONCLUSION: The ability of steroids to induce ultrastructural features of improvement supports the notion that they have beneficial therapeutic role. The clinical ramifications of these observations mandate further studies.

Primary small cell neuroendocrine carcinoma of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural evaluation.

Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder is a rare but aggressive neoplasm that usually exhibits neuroendocrine differentiation. Here, the authors report a case of SCNEC in an 80-year-old man. The patient had gross hematuria and nodular mass involving the wall of the urinary bladder. Total cystectomy was done. The tumor consisted of small, uniform, round, and spindled-shaped cells with chromatin dark nuclei and numerous mitotic figures. The cells were reactive for chromogranin, neuron-specific enolase (diffuse), and keratin (focal). Ultrastructural studies revealed neurosecretory granules and intermediate filaments. The diagnosis of SCNEC with focal high-grade urothelial component was established. No metastasis was found at the time of diagnosis and the patient refused further chemotherapy or radiotherapy. The histogenesis, differential diagnosis, and prognosis of SCNEC of the urinary bladder were discussed.

Leukemia cutis: case report and review of literature.

Leukemias are neoplasms of hematolymphoid cells that predominantly involve the peripheral blood. Cutaneous involvement (leukemia cutis) occurs in chronic myeloid leukemia, chronic lymphocytic leukemia, and in monocytic leukemia. Here, we report a case of a 49-year-old female patient known to have chronic myeloid leukemia presented with multiple cutaneous lesions. The clinicopathologic features were presented and the relevant literature was discussed.

Expression of Ras homologous B protein in the human scalp skin and hair follicles: hair follicle cycle stages-associated changes.

BACKGROUND: RhoB belongs to the Ras homologous (Rho) subfamily which consists of low molecular weight mass GTP-binding proteins. Rho proteins are regulatory molecules that mediate changes in cell shape, contractility, motility and gene expression. AIM: To test the hypothesis that 'RhoB protein is expressed in the human skin and its expression undergoes hair follicle cycle dependent changes'. To test this hypothesis, we examined the expression of RhoB in the normal human skin and hair follicles (HFs) using immunohistochemical methods. METHODS: A total of 50 normal human scalp skin specimens were obtained from 50 females (age: 53-57 years) undergoing elective cosmetic plastic surgery. The specimens were obtained from both frontal and temporal regions of the scalp. A total of 50 HF, (35 anagen, 10 catagen and 5 telogen) were examined in each case using immunohistologic staining methods. Semiquantitative analysis was done. RESULTS: RhoB protein was strongly expressed in the various elements of the human scalp skin and hair follicles. In the epidermis, a moderate RhoB immunoreactivity was found in all layers except stratum corneum where RhoB protein was completely absent. In sebaceous glands, a strong RhoB immunoreactivity was detected in all sebaceocytes. In the hair follicles, the expression of RhoB protein showed hair follicle cycle stages-associated changes, i.e. strong expression during anagen, but weak and completely absent expressions during catagen and telogen phases, respectively. Semiquantitative analysis revealed statistically significant high expression values (staining intensity, percentage of positive cells and immunoreactivity scores) in the anagen VI hair follicles compared to either cantagen or telogen ones (p < 0.05). Similarly, RhoB protein expression was significantly high in the stratum basale, stratum spinosum and sebaceous glands compared to stratum granulosum (p < 0.05). CONCLUSIONS: Here we report, for the first time, the distribution of RhoB protein in the human scalp skin and hair follicles. We also provide the first indication that there are variations in the expression of this protein in the different stages of the hair cycle.

Skin-limited Langerhans' cell histiocytosis in children.

Langerhans' cells are dendritic cells derived from precursors in the bone marrow. They constitute 2-4% of the resident epidermal cells and are found within the epidermis above the basal layer. They function as immunologic cells by recognizing antigens and presenting them to T cell lymphocytes. Langerhans' cell histiocytosis is a rare pathology characterized by an abnormal clonal proliferation of Langerhans' cells that infiltrates different organs of the human body. The proliferating Langerhans' cells appears to be primarily responsible for the clinical manifestations. The stimulus for their proliferation is unknown. Among different organs, cutaneous involvement is encountered in 40% of cases. The aim of this investigation is to review the clinicopathologic, immunologic and ultrastructural features of skin-confined Langerhans' cell histiocytosis in children through seven case series. Four boys and two girls with age range of 1 year to 8 years presented with scaling, crusted papules, nodules and papulonodular lesions (two cases each). The locations included the face (three cases), scalp, trunk and vulva (one case each). The histological features included histiocytic reaction (one case), granulomatous reactions (three cases) and both granulomatous and histiocytic reactions (two cases). The diagnosis was confirmed by histochemical (S-100 + CD1a +) and ultrastructural studies (Birbeck granules). Langerhans' cell histiocytosis is a rare disease with pleomorphic cutaneous clinical expressions. Three types of skin lesions usually occur: nodules (common), scaling, or crusted papules (next in frequency) and finally soft, yellow papular xanthomas (rare). Three types of histological pictures are seen: histiocytic, granulomatous (common) and xanthomatous (rare).

Analysis of hMSH2 mismatch repair protein expression in dysplasia, carcinoma in situ and invasive squamous cell carcinoma of the vocal folds.

UNLABELLED: The expression pattern of hMSH2 mismatch repair protein during the progression of benign epithelium to vocal fold invasive squamous cell carcinoma has not been previously described. Nor has the correlation between the hMSH2 protein expression and the clinicopathologic features of the vocal fold dysplasia and carcinoma been examined. HYPOTHESIS: "The progression of benign epithelium to invasive squamous cell carcinoma of the vocal folds is associated with reduction of the hMSH2 mismatch repair protein expression." METHODS: Vocal fold biopsies were obtained from 20 patients with mild and moderate dysplasia: 10 patients with severe dysplasia (squamous cell carcinoma in situ) and 20 patients with invasive squamous cell carcinoma. The expression pattern of hMSH2 protein was examined by using immunoperoxidase-staining methods and mouse monoclonal antibodies. The results were scored as the percentage of hMSH2 positively stained cells. RESULTS: The mean values of hMSH2 positively stained cells decreased gradually with the transitions from normal epithelium to dysplasia and finally to invasive squamous cell carcinoma. There was a negative correlation between the expression of hMSH2 and the degree of dysplasia, that is, as the severity of the dysplasia increases at the microscopic level, there was a decrease in the expression values of the hMSH2 protein. CONCLUSIONS: We report, for the first time, that the reduced expression of the hMSH2 mismatch repair protein is related to the progression of the benign epithelium to invasive squamous cell carcinoma of the vocal folds.

Expression pattern of p75 neurotrophin receptor protein in human scalp skin and hair follicles: Hair cycle-dependent expression.

BACKGROUND: The p75 neurotrophin receptor (p75NTR) is a death factor (apoptosis-promoting protein) that belongs to the tumor necrosis factor receptor superfamily of membrane proteins. In the murine hair follicle (HF) model, p75NTR plays a critical role during HF morphogenesis, functioning as a receptor that negatively controls HF development. p75NTR signaling is involved in the control of keratinocyte apoptosis during catagen. To date, knowledge about the expression pattern of p75NTR protein in human scalp skin and HFs is limited. In this investigation we hypothesized that p75NTR protein is expressed in human scalp skin and its expression in HFs fluctuates with the transitions from anagen --> catagen --> telogen stages. METHODS: To test this hypothesis, the immunoreactivity of p75NTR protein was examined in human scalp skin by immunofluorescent and immunoalkaline phosphatase methods. A total of 50 normal-appearing human scalp skin biopsy specimens were examined (healthy women age 53-57 years). In each case, 50 HFs were analyzed (35, 10, and 5 follicles in anagen, catagen, and telogen, respectively). RESULTS: We found variations in p75NTR protein expression with HF cycling. p75NTR expression was negligible in early, mid, and mature anagen and weak during late anagen. p75NTR expression was moderate during anagen-catagen transition. It was strong in both catagen and telogen HF. Also, p75NTR protein expression was strong in the stratum corneum (epidermis), dermal fibroblasts, blood vessels, nerve endings, adipocytes, and both sebaceous and sweat glands. LIMITATIONS: Our knowledge about other proteins (prosurvival and pro-apoptotic molecules) interacting with p75 is incomplete. CONCLUSIONS: Our investigation reports, for the first time, the expression patterns of p75NTR in human scalp skin and HFs. p75NTR protein expression exhibited significant hair cycle-dependent fluctuation, suggesting a possible role in human HF biology.

Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma.

BACKGROUND: Immune cell infiltrate is a constant feature in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. This study elaborates on the cells of the immune system present in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. HYPOTHESIS: Here, we hypothesized that "the development of benign nodular prostatic hyperplasia and prostatic adenocarcinoma is associated with numeric alterations of the immune cell infiltrate". MATERIALS AND METHODS: A total of 50 transurethral prostatic resection specimens, each entailing normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma were evaluated for the density and phenotype of the immune cells using immunohistological methods and mouse monoclonal antibodies decorating T cells (CD3), histiocytes (CD68) and B lymphocytes (CD20). RESULTS: Immune cell infiltrate was composed of T cells, histiocytes and B-lymphocytes. CD(+)3 T lymphocytes and CD68(+) cells were the predominant cell populations. We observed variations in the density of the immune cells among the normal prostate, benign nodular prostatic hyperplasia and high grade prostatic adenocarcinoma. Compared with normal prostate, benign nodular prostatic hyperplasia had a statistically significant high density of immune cells (3.4+/-0.4versus 13.5+/-1.0, P<0.00). In contrast, a significant decrease in the counts of these cells was observed in high-grade prostatic adenocarcinoma compared to benign nodular prostatic hyperplasia (13.5+/-1.0 versus 5.2+/-0.3, P<0.01). CONCLUSIONS: The increased density of immune cells (predominantly CD(+)3 T cells) in benign nodular prostatic hyperplasia suggests that the initial response to cellular damage is mediated by cell-mediated immunity. The decreased density of immune cells in high-grade prostatic adenocarcinoma may reflect immunosuppression. The underlying mechanisms of these numeric variations are open for further investigations.

Phenotypical characteristics of the immune cells in allergic contact dermatitis, atopic dermatitis and pityriasis rosea.

Allergic contact dermatitis (ACD) is a cell-mediated, delayed type IV immunologic reaction. Atopic dermatitis (AD) is a chronic inflammatory skin disease that results from a complex interaction between immunologic, genetic, and environmental factors. Pityriasis rosea (PR) is a self-limited eruption of unknown etiology. Immune cell infiltrate is a constant feature in the inflammatory skin diseases. Here, we performed phenotypical characterization of the immune cells in ACD, AD and PR (ten cases each). We performed immunohistochemical stains for B cells (CD20), T cells (CD3), histiocytes (CD68) and T cells with cytotoxic activity (granzyme-B). The data were compared with findings in 20 specimens of normal skin. The results were scored as mean values of positively stained immune cells. Immunohistochemistry showed significantly high counts of immune cells in lesional skin (ACD, AD and PR) compared to the normal one (p < 0.05). In the lesional skin, the immune cells were composed predominantly of CD3(+) T lymphocytes and CD68(+) cells (histiocytes). Some of the CD3(+) cells were granzyme B(+). The counts of some immune cells (CD3(+) and CD68(+)) were high in ACD compared to AD and PR. The counts of CD20(+) and granzyme B(+) cells were high in PR compared to ACD and AD. However, these differences did not reach the level of statistical significance. The present data describe the profile of the immune cell infiltrate in AD, ACD and PR. The cell-mediated immunity seems to have critical role in the development of these lesions.

Heat shock protein 27 expression in the human testis showing normal and abnormal spermatogenesis.

Heat shock proteins (HSPs) are molecular chaperones involved in protein folding, assembly and transport, and which play critical roles in the regulation of cell growth, survival and differentiation. We set out to test the hypothesis that HSP27 protein is expressed in the human testes and its expression varies with the state of spermatogenesis. HSP27 expression was examined in 30 human testicular biopsy specimens (normal spermatogenesis, maturation arrest and Sertoli cell only syndrome, 10 cases each) using immunofluorescent methods. The biopsies were obtained from patients undergoing investigations for infertility. The seminiferous epithelium of the human testes showing normal spermatogenesis had a cell type-specific expression of HSP27. HSP27 expression was strong in the cytoplasm of the Sertoli cells, spermatogonia, and Leydig cells. Alternatively, the expression was moderate in the spermatocytes, weak in the spermatids and absent in the spermatozoa. In testes showing maturation arrest, HSP27 expression was strong in the Sertoli cells, weak in the spermatogonia, and spermatocytes. It was absent in the spermatids and Leydig cells. In Sertoli cell only syndrome, HSP27 expression was strong in the Sertoli cells and absent in the Leydig cells. We report for the first time the expression patterns of HSP27 in the human testes and show differential expression during normal spermatogenesis, indicating a possible role in this process. The altered expression of this protein in testes showing abnormal spermatogenesis may be related to the pathogenesis of male infertility.

The postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin: preliminary findings.

This study examines the postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin. Three groups of nasal mucosal biopsies were obtained from 20 patients having undergone nasal surgery (partial middle turbinectomy). The first group was obtained immediately before surgery (control group). The second and third groups were taken postoperatively (after the first and 6 weeks of amoxycilline or rifampicin therapy, 10 patients each). The histologic changes in the nasal mucosa and the density of seromucinous glands were examined using histochemical methods and image analyzer. Amoxycilline treatment was associated with squamous metaplasia and a statistically significant reduction in the percent area of the seromucinous glands compared to the control group (p < 0.05). Rifampicin therapy was associated with minimal reduction in the density of the seromucinous glands and absence of metaplastic changes. In nasal surgeries, rifampicin but not amoxycilline had a beneficial effect on postoperative nasal mucosa status.