cyclin-d1 and Conjunctival-Neoplasms

Ocular surface squamous neoplasia (OSSN) can recur, metastasize, and even cause death. Cyclins regulate the cell cycle progression at different phases and its dysregulation is associated with uncontrollable cell growth and malignant transformation of the cell. Overexpression of cyclin has been reported in various malignancies and is associated with poor prognosis. However, the role of cyclins in OSSN remains unexplored. This study has been designed to assess the prognostic significance of cyclin (cyclin B1, E1, and D1) immunoexpression in 100 OSSN patients. The targeted proteins demonstrated overexpression of cyclin B1, cyclin E1, and cyclin D1 in 55%, 37%, and 56% OSSN cases prospectively. A gradual and significant increase in the cyclin B1 (P=0.01) and cyclin D1 (P=0.005) expression was seen from Tis to the T4 category. Overexpression of cyclin B1 was associated with poor disease-free survival and worst prognosis in both early (P=0.03) as well as advanced T staged (P=0.038) OSSN patients. Overexpression of cyclin E1 was associated with worst disease-free survival (P=0.01) and poor prognosis in advanced stage OSSN patients. Our findings suggest that cyclin B1 and cyclin E1 have prognostic relevance in OSSN patients, and therefore are recommended for detecting high-risk category cases. A significant increase in the expression of cyclins from early to advanced stage indicates that cyclins play an important role in the pathogenesis of OSSN patients.

Topics: Carcinoma, Squamous Cell; Conjunctival Neoplasms; Cyclin B1; Cyclin D1; Humans; Neoplasm Recurrence, Local

Deep penetrating nevus (DPN) is not a widely recognised lesion on the conjunctiva and only a few cases consistent with combined DPN have been reported.. A review of all excised and histopathologically diagnosed conjunctival melanocytic lesions between 2003 and 2018 was performed in order to identify melanocytic nevi morphologically consistent with DPN.. Thirty-four DPN were identified among 361 histopathologically examined conjunctival nevi (9.4%), including 33 (97%) combined with a common nevus and 1 (3%) pure DPN. The patients' age ranged from 7 to 51 years (median, 22 years). Clinically, 21 of 29 (72%) lesions with available data were darkly pigmented, and an increase in size and/or pigmentation was noted in 13 of 18 (72%) lesions with known history. All 24 lesions in which an immunohistochemical analysis was possible were diffusely positive for BRAFV600E (in DPN and common nevus components) and showed a diffuse nuclear positivity for beta catenin and cyclin D1 in the DPN component. None of the 21 lesions with available follow-up data recurred during a follow-up period from 0.3 to 16.3 years (median, 7.5 years).. DPN of the conjunctiva is a relatively common lesion and usually presents as a combined nevus. Genetically, DPN of the conjunctiva are characterised by a combination of BRAFV600E mutation and activation of the beta catenin pathway. Recognition of DPN of the conjunctiva is important in order not to overdiagnose it as a melanoma, and to explain its potential atypical clinical features. DPN of the conjunctiva seems to be a benign lesion.

Topics: Adolescent; Adult; beta Catenin; Child; Conjunctival Neoplasms; Cyclin D1; Female; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; Nevus, Pigmented; Proto-Oncogene Proteins B-raf

Conjunctival squamous cell carcinoma (SCC) is the most common tumor of conjunctival epithelium. It is associated with risk of permanent visual impairment and has the capability to recur, metastasize, and cause death. Deregulation of cell cycle control has been reported in a number of malignancies. The aim of the present study was to assess expression of G1/S cell cycle regulatory proteins [retinoblastoma protein (pRb)/P16/cyclin D1] in conjunctival SCC. Forty-four prospective cases of conjunctival SCC from a tertiary eye care referral center in northern India were included in this study. American Joint Committee on Cancer (AJCC) staging was performed and patients were followed up for 46±3.2 months. pRb loss was seen in 87% and overexpression of p16 and cyclin D1 in 36% and 66%, respectively. Kaplan-Meier analysis revealed reduced disease-free survival in patients with pRb loss (P=0.006). On univariate analysis, pRb loss (P=0.02), orbital invasion (P=0.03), and AJCC stage ≥T3 (P=0.03) emerged as significant high-risk features. On multivariate analysis pRb loss emerged as the most significant poor prognostic indicator in conjunctival SCC cases. Our findings suggest pRb loss to be a useful indicator of aggressive behavior and is recommended for identifying high-risk conjunctival SCC patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Child; Conjunctival Neoplasms; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p16; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Retinoblastoma Protein; Survival Analysis; Young Adult

Even in experienced hands, the classification of some melanocytic lesions of the conjunctiva remains challenging. In skin pathology, the recent application of fluorescence in situ hybridisation (FISH) has been demonstrated to be of use for the analysis and diagnosis of ambiguous melanocytic neoplasms of the skin. This study set out to evaluate this method on seven prospective conjunctival cases that were histologically equivocal.. 18 unequivocal retrospective melanocytic controls were exposed to FISH. Commercially available probes assessing copy numbers of RREB1 (6p25), MYB (6q23) and CCND1 (11q13) genes compared with CEP6 (a chromosome six centromeric reference point) were used. After control verification, seven prospective, equivocal cases were identified and exposed to FISH.. There was complete correlation between FISH result and the control section histopathology report. Control cases of melanoma cases were all positive for FISH and control benign lesions were negative. Of the seven equivocal cases, five were positive and classed as invasive melanoma or melanoma-in situ, one was negative and one tetraploid, classed as negative (these last two cases were classed as naevi with careful clinical observation).. FISH is very useful in classifying equivocal conjunctival melanocytic lesions, especially those with atypical junctional activity and naevoid melanocytic proliferations of the conjunctiva.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Conjunctival Neoplasms; Cyclin D1; DNA Probes; DNA-Binding Proteins; Female; Humans; In Situ Hybridization, Fluorescence; Male; Melanoma; Middle Aged; Neoplasm Proteins; Nevus, Pigmented; Prospective Studies; Proto-Oncogene Proteins c-myb; Retrospective Studies; Transcription Factors; Young Adult

To describe a rare manifestation of mantle cell lymphoma (MCL) in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature.. Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14).. A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

Topics: Antigens, CD; Conjunctiva; Conjunctival Neoplasms; Cyclin D1; Gene Expression; Humans; Lymphoma, Mantle-Cell; Male; Middle Aged; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-bcl-2; SOXC Transcription Factors; Translocation, Genetic

Most primary ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as conjunctival mass. A 58-year-old man presented with a palpable mass in the left lower tarsal conjunctiva incidentally detected one month previously. Histopathologic examination showed proliferation of monomorphous small-to-medium sized lymphoid cells. On immunohistochemistry, tumor cells were positive for CD20, bcl-2, and cyclin D1, and negative for CD5. PCR analysis for immunoglobulin heavy chain gene rearrangement showed monoclonal B-cell proliferation. t(11;14)(q13;q32), involving the CCND1 and IGH genes, was detected in interphase fluorescent in situ hybridization using formalin-fixed, paraffin-embedded tissue; however, MALT1 gene translocation was not observed. The final diagnosis was mantle cell lymphoma. There was no lymphadenopathy; however, bone marrow involvement of the lymphoma was suspected. The patient has been receiving systemic chemotherapy. This case emphasizes the differential diagnosis of conjunctival mantle cell lymphoma from extranodal marginal zone B-cell lymphomas of MALT regarding the clinical and pathological aspects.

Topics: Antineoplastic Combined Chemotherapy Protocols; CD5 Antigens; Cell Proliferation; Conjunctival Neoplasms; Cyclin D1; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Gene Rearrangement, B-Lymphocyte; Humans; Immunoglobulin Heavy Chains; Immunohistochemistry; In Situ Hybridization, Fluorescence; Incidental Findings; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Male; Middle Aged; Translocation, Genetic