Salem Alowami

Mammographic density is related to stroma and stromal proteoglycan expression

BackgroundMammographic density and certain histological changes in breast tissues are both risk factors for breast cancer. However, the relationship between these factors remains uncertain. Previous studies have focused on the histology of the epithelial changes, even though breast stroma is the major tissue compartment by volume. We have previously identified lumican and decorin as abundant small leucine-rich proteoglycans in breast stroma that show altered expression after breast tumorigenesis. In this study we have examined breast biopsies for a relationship between mammographic density and stromal alterations.MethodsWe reviewed mammograms from women aged 50–69 years who had enrolled in a provincial mammography screening program and had undergone an excision biopsy for an abnormality that was subsequently diagnosed as benign or pre-invasive breast disease. The overall mammographic density was classified into density categories. All biopsy tissue sections were reviewed and tissue blocks from excision margins distant from the diagnostic lesion were selected. Histological composition was assessed in sections stained with haematoxylin and eosin, and the expression of lumican and decorin was assessed by immunohistochemistry; both were quantified by semi-quantitative scoring.ResultsTissue sections corresponding to regions of high in comparison with low mammographic density showed no significant difference in the density of ductal and lobular units but showed significantly higher collagen density and extent of fibrosis. Similarly, the expression of lumican and decorin was significantly increased.ConclusionAlteration in stromal composition is correlated with increased mammographic density. Although epithelial changes define the eventual pathway for breast cancer development, mammographic density might correspond more directly to alterations in stromal composition.

TdT expression in Merkel cell carcinoma: potential diagnostic pitfall with blastic hematological malignancies and expanded immunohistochemical analysis.

Merkel cell carcinoma is an uncommon aggressive primary cutaneous neuroendocrine carcinoma. Histologically, the differential diagnosis includes the ‘small round cell’ tumor group, particularly metastatic small cell carcinoma and blastic hematological malignancies involving skin/soft tissues. Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase, which is a sensitive and specific antibody for acute lymphoblastic lymphoma with a small proportion of acute myeloid leukemia showing positivity. This study investigates the expression of TdT in 20 cases with initial diagnosis of Merkel cell carcinoma. Archival blocks and slides were retrieved and reviewed and clinical information obtained from patient charts. Immunohistochemistry was performed and graded as: 0, no staining; 1+, less than 50% staining in the cells; 2+, 50% or more staining in the cells. After review, 15 cases were confirmed as Merkel cell carcinoma. Immunohistochemical positivity was as follows: 8/15 cases were positive for TdT with strong nuclear staining, morphologically resembling ‘blasts’, AE1AE3, CAM5.2 (15/15) (both membrane and paranuclear dot positivity), CD56 and BCL-2 (15/15), Synaptophysin (13/15), Chromogranin A (11/15), NSE (15/15), CK20 (14/15), CK7 (3/15), both CK7 and CK20 (3/15), CD117 (8/15), CD99 (2/15), CD10 (1/15). One case was negative for CK7/CK20. All 15 cases were negative for thyroid transcription factor-1, LCA, CD20, CD3 and CD34. Expanded immunohistochemical panel with positive staining for epithelial/neuroendocrine markers, CK20, negative staining for hematolymphoid markers and awareness of TdT expression and other markers that show overlap with blastic hematological malignancies avoids misinterpretation in the diagnosis of Merkel cell carcinoma. This aids in further diagnosis of Merkel cell carcinoma, avoiding the potential diagnostic pitfall with other small round cell tumors and hematological malignancies primary or metastatic to the skin.

Psoriasin (S100A7) expression is altered during skin tumorigenesis

BackgroundPsoriasin (S100A7) expression has previously been associated with psoriasiform hyperplasia as well as with tumor progression in breast cancer. Its expression profile for different stages of skin lesions is unknown. The aim of this study was to determine the relationship between psoriasin (S100A7) and tumor progression in skin.MethodsPsoriasin was assessed by immunohistochemistry and levels of expression determined by semi-quantitative scoring in skin biopsies from 50 patients. The cohort included normal skin, actinic keratosis, squamous carcinoma in-situ, invasive squamous cell carcinoma, and basal cell carcinoma.ResultsIn normal skin, psoriasin was rarely detected in epidermis but was expressed in underlying adnexae. In abnormal epidermis psoriasin was frequently expressed in abnormal keratinocytes in actinic keratosis, in-situ and invasive squamous cell carcinoma, but was rarely observed in the basal epidermal layer or in superficial or invasive basal cell carcinoma. The highest levels of expression were seen within squamous carcinoma in-situ. Significantly reduced levels of expression were observed in both unmatched (p = 0.0001) and matched (p < 0.004) invasive squamous cell carcinoma. Psoriasin expression within abnormal squamous lesions correlated with mitotic count (r = 0.54, p = 0.0036), however no significant relation was found with the intensity of dermal inflammatory cell infiltrates assessed within each pathology.ConclusionThese results suggest that altered psoriasin expression occurs in abnormal epidermis and that downregulation may be related to the onset of invasion in squamous cell carcinoma in skin.

S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast

IntroductionThe S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1.MethodsIn order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry.ResultsS100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27kip1 (n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36).ConclusionThe findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1.

The Role of HER‐2/neu Oncogene and Vimentin Filaments in the Production of the Paget's Phenotype

Abstract:  The histogenesis as well as the biological and molecular differences in mammary Pagets disease (MPD) and extramammary Pagets disease (EPD) are not well understood. HER‐2/neu oncogene overexpression is associated with poor prognosis in breast cancer patients. It is also believed that the spread of Pagets cells through the epidermis is induced by a motility factor that acts via the HER‐2/neu receptor. However, previous studies on HER‐2/neu expression in MPD and EPD have given conflicting results. Recent studies have suggested that vimentin expression in breast cancer confers a more aggressive phenotype with a possible role in tumor invasion and metastasis. We examined 58 cases of MPD and EPD for HER‐2/neu overexpression and vimentin status to study the role of these markers in the production of the Pagets phenotype. Thirty‐five of the 38 cases (92.1%) of MPD were associated with an underlying carcinoma, while none of the cases of EPD were associated with an underlying malignancy. Thirty‐six of the 38 cases of MPD (94.7%) overexpressed the HER‐2/neu oncoprotein and 17 cases (44.7%) showed vimentin expression. In contrast, only 1 of the 20 cases of EPD (5%) showed positivity for HER‐2/neu oncoprotein and all were negative for vimentin. Our results indicate that the cell motility enhancing effect of HER‐2/neu oncoprotein and possibly vimentin plays a significant role in the pathogenesis of MPD which appears to be a pagetoid spread of an underlying ductal malignancy (secondary), while EPD is an in situ malignant transformation of a totipotential epidermal cell or glandular epithelium. 

Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

BackgroundThe human psoriasin (S100A7) gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis.MethodsOn the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization) with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7.ResultsAlthough mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene.ConclusionThese observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.

Synchronously diagnosed lymph nodal collision tumor of malignant melanoma and chonic lymphocytic leukemia/small lymphocytic lymphoma: case report

Synchronous composite tumors have been described but are uncommon. Moreover, simultaneous occurrence of synchronous tumors in the same tissue or organ is even less common. We report a case of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and malignant melanoma (MM) occurring synchronously in the same lymph node. Several cases of an association between cutaneous malignancies and lymphoproliferative disorders have been reported. Some of which included CLL and MM, occurring in the same patient often CLL after MM. The risk of having CLL after MM has been reported to be increased. Various genetic and environmental etiologies have been postulated, but have as yet not been proven. To our knowledge this is the first time that synchronous occurrence of these two malignant processes in the same tissue is described. In this case it is important that the melanoma was recognized in the excised lymph node, as this finding had much more critical treatment and long term survival consequences.

Signet ring squamous cell carcinoma--the forgotten variant: case report and review of the literature.

Squamous cell carcinoma is one of the commonest skin cancers. In most instances, histological diagnosis is straightforward and does not pose any diagnostic challenge to the handling pathologist. We report a rare case of signet ring squamous cell carcinoma (SRSCC) occurring in an 84‐year‐old woman who presented with a sore on the upper lip. Excision of the lesion showed signet ring carcinoma within a scar and surface ulceration. Deeper sections showed focal area of squamous differentiation.

Intra-articular nodular fasciitis of the shoulder: a case report and review of the literature

Nodular fasciitis is a benign proliferation of myofibroblasts usually arising adjacent to the fascia. In this report, we describe a rare case in which nodular fasciitis occurred in an intra-articular location in the shoulder of a 26-year-old man. The mass developed in the subscapularis recess of the shoulder and histological evaluation showed a myofibroblastic proliferation. MRI findings of intra-articular nodular fasciitis are discussed along with a review of previous reports.

Sebaceoma of the external ear canal: an unusual location. Case report and review of the literature

Sebaceous neoplasms of the external ear canal are extremely rare. Only two cases of sebaceous neoplasms have been reported in the English literature, a sebaceous carcinoma and a sebaceous adenoma. We report a case of sebaceoma of the external ear canal. To the best of our knowledge, sebaceoma of the auditory canal has not been reported previously. We highlight the differential diagnosis, particularly sebaceous carcinoma and basal cell carcinoma with sebaceous differentiation. Awareness of the possible occurrence of sebaceoma in the auditory canal may prevent the diagnostic pitfall of misidentifying this tumor.