Indolent CD8+ primary cutaneous T-cell lymphoma involving the eyelid of an adolescent.

Primary cutaneous acral CD8+ T-cell lymphoma (PCACTL) is currently a provisional entity defined as a rare cutaneous proliferation of atypical CD8+ lymphocytes that preferentially involves acral sites and has a good prognosis. We present a case of primary cutaneous CD8+ T-cell lymphoma involving the eyelid of an adolescent male. The case shares features with PCACTL, including indolent clinical behavior and expression of CD68 in a Golgi-associated dot-like pattern; however, other features differ significantly from PCACTL as currently defined by the World Health Organization (WHO). These features include ulceration, expression of CD56, granzyme B, and perforin, and a high proliferative index. Given these discrepancies, our case is currently best classified as a CD8+ primary cutaneous peripheral T-cell lymphoma, not otherwise specified. We review the differential diagnosis for this case and suggest expanding the definition of PCACTL.

'The nodule that disappeared' spontaneous regression of an eyelid noduloulcerative lesion mimicking the features of a basal cell carcinoma.

We describe a case of a clinically apparent basal cell carcinoma (BCC) with spontaneous regression. Histological confirmation of the diagnosis was not possible, and an immunological basis for regression is presumed. The understanding of such immunologically mediated regression of BCCs could provide future therapeutic targeting and research is ongoing.

[Immunoglobulin-G4-related disease: a challenging diagnosis]. / Boala legata de imunglobulinele G4: provocare diagnostica.

INTRODUCTION: Immunglobulin G4 (IgG4)-related disease was recently described and represents a systemic lymphoproliferative disorder. The orbital form of the disease manifests as chronic lid swelling and proptosis. Visual disturbances may occur due to apical orbital lesions. CASE REPORT: A 65-year old pacient presents with the impossibility of maintaining his right eye open due to a progressive swelling of the upper lid. The general clinical examination shows adenopathy at 3 lymph node stations of the head. On ophthalmologic examination, a large tumor of the upper lid is observed in the right eye and proptosis and central retinal vein occlusion are noted in the left eye. The serum levels of the IgG are very high. A lymph node biopsy was performed. DISCUSSION: The differential diagnosis between the IgG4-related orbital disease and non-Hodgkin lymphoma is discussed. CONCLUSION The diagnosis criteria for IgG4-related disease are both the high serum levels of IgG4 and the specific immunohistochemistry stains.

Clinical significance of tumor-infiltrating FOXP3+ T cells in patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma.

We evaluated the association between tumor-infiltrating FOXP3+ T cells and clinical outcomes in patients with ocular adnexal lymphoma of mucosa-associated lymphoid tissue type (OAML). Pretreatment formalin-fixed paraffin-embedded tissues from 42 patients with OAML were stained with 236A/E7 anti-FOXP3 murine monoclonal antibody as well as CD3, CD4 and CD8 antibodies. The amount of FOXP3+ T cells was numerically quantified using an image analysis program. Front-line treatments were as follows: combination chemotherapy (n = 25); radiotherapy (n = 9); doxycycline (n = 6); and wait and see (n = 2). Complete response (CR) was observed in 20 (50%) of 40 evaluable patients. Median progression-free survival (PFS) was 50 months. A high number of FOXP3+ T cells (n = 21, ≥ 180/0.58 mm(2)) showed a higher CR rate (33%vs 71%, P = 0.013) and tendency towards prolonged PFS (48 vs 67 months, P = 0.110). In the combination chemotherapy group, a high number of FOXP3+ T cells was significantly associated with a higher CR rate (29%vs 82%, P = 0.008) and prolonged PFS (17 vs 79 months, P = 0.003). A high number of tumor-infiltrating FOXP3+ T cells correlates with a favorable clinical outcome in OAML patients.

Rituximab immunotherapy for ocular adnexal lymphoma: clinicopathologic correlation with 5-year follow-up.

Two patients with primary ocular adnexal mucosa-associated lymphoid tumor lymphoma were treated with rituximab immunotherapy. One patient had refused radiotherapy. The other had bilateral ischemic retinopathy, a relative contraindication to radiotherapy. Biopsies were performed 6 months after treatment. One patient had complete resolution of local disease, and the other had a partial response, remaining stable without signs of progression. During the 5 years of clinical follow-up, there was no evidence of systemic disease in either patient. Rituximab immunotherapy is an alternative to regional radiotherapy for ocular adnexal mucosa-associated lymphoid tumor lymphoma.

Cutaneous presentation on the eyelid of primary, systemic, CD30+, anaplastic lymphoma kinase (ALK)-negative, anaplastic large-cell lymphoma (ALCL).

AIM: To report an unusual case of cutaneous presentation on the eyelid of systemic (or nodal), CD30+, anaplastic large-cell lymphoma (ALCL). METHODS: A 39-year-old man presented with a rapidly growing exophytic mass on the left upper eyelid, with a protuberant, ulcerated aspect and with discharge. The patient showed lymph node involvement 3 months after the appearance of the lesion on the eyelid (the lesion itself appeared 1 week before examination). RESULTS: The histopathologic and immunohistochemical diagnosis was ALCL, T-cell phenotype, strongly positive for CD43 and CD30, and negative for CD3, anaplastic lymphoma kinase (ALK), and B-cell antigens. Treatment was by radiotherapy and, later, chemotherapy (cyclophosphamide, adriamycin, vincristine, and prednisolone, CHOP) for skin recurrences and lymphadenopathies over 5 years. There has been no recurrence for more than 6 years. CONCLUSIONS: Primary, systemic, CD30+, ALK-negative, ALCL presentations generally have a poor prognosis and tend to occur in older individuals, although the clinical outcome is highly variable and difficult to predict in individual cases. Only three cases of ALCL have been described in the ocular adnexae and none was ALK-negative.

Immunology and growth characteristics of ocular basal cell carcinoma.

BACKGROUND: Knowledge about immunological features and growth characteristics of palpebral (ocular) basal cell carcinomas (BCCs) is limited. In particular, it is unclear whether ocular BCC represents in this regard a special BCC entity or not. METHODS: Twenty BCCs of the lid area (ocular BCCs) were investigated immunohistologically using monoclonal antibodies against CD4, CD8, CD45Ro, CD50, CD68, HECA-452, Ki67 (MIB1), and the p53 epitope. For comparison, nine BCCs excised distant from the eye (non-ocular BCCs) were evaluated. RESULTS: In BCCs the distribution of the immunocompetent cells investigated is markedly irregular. These cells are localized mainly around BCC islands. Only a few of them invade tumour cell aggregates. The CD4:CD8 ratio as detected by immunohistochemistry is >1 in 82% of ocular BCCs and in 88% of nonocular BCCs. Often there are dense infiltrations of CD68+ cells (macrophages) and HECA-452+ cells adjacent to tumour cell aggregates. The growth fraction [percentage of proliferating (Ki67+/MIB 1+) cells] varies from 0% to more than 30%. Proliferative activity is enhanced at the invasion front. Additionally, the amount of p53+ cells differs considerably among the BCCs. CONCLUSIONS: CD4+ T cells seem to be the most important cell population for BCC immunosurveillance, offering the chance for conservative interferon therapy. The role of CD68+ and HECA-452+ cells has to be further elucidated. In many tumours the large amount of proliferating cells contrasts to the usually slow growth of BCCs, indicating strong apoptotic processes. The results can be regarded only as semiquantitative. So far, ocular and nonocular BCCs exhibit no essential differences regarding immunocompetent cell infiltration and growth characteristics. According to this, palpebral BCCs are "normal" BCCs and not a special BCC variant. Therefore, results from dermatological research concerning BCC can be extended without limitations to their counterparts in the lid area.

Six-year disease-free survival of a patient with metastatic eyelid squamous cell carcinoma and colon adenocarcinoma after repeated postoperative adoptive immunotherapy.

A 74-year-old male was affected concurrently with squamous cell carcinoma of the left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He underwent exenteration of the left orbit with left modified radical neck dissection and subsequently resection of the transverse colon with regional lymph node dissection. The patient has been treated by an adoptive immunotherapy as a sole postoperative modality without receiving any chemotherapeutic agents causing immunosuppression. For the adoptive immunotherapy, autologous peripheral blood lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14 days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been repeated 150 times in total at the time of writing. Neither recurrence nor additional metastasis has been detected for 6 years after surgery.

Solitary extranodal anaplastic large cell lymphoma, Ki-1+, of the eyelid.

PURPOSE: To report a rare case of solitary anaplastic large cell lymphoma, Ki-1+, of the eyelid. METHOD: Case report. A firm ulcerated mass of the lower eyelid in a 10-year-old boy was the initial and only sign of anaplastic large cell lymphoma. RESULTS: A local excision of the mass was performed. Histologic examination disclosed large lymphoid anaplastic cells that reacted positively for T-cell markers and CD30 antigen. CONCLUSION: A solitary eyelid mass can be an initial sign of anaplastic large cell lymphoma in children.

[Changes in the immune status in patients with basal cell carcinoma of the eyelids of various TNM stages]. / Veränderungen des Immunstatus bei Patienten mit Basalzellkarzinom der Lider in verschiedenen TNM-Stadien.

Various lymphocyte populations/subpopulations--Leu-4+ (CD3+), Leu-2+ (CD8+), CD4+/CD8+ ratio, Leu-14+ (CD22+), Leu-M5+ and HLA-DR+--were studied in 104 patients with basal cell carcinoma (BCC) of the eyelid in different TNM stages by Coulter EPICS flow cytometry preoperatively. For comparison, an age-matched control group of 60 clinically healthy individuals (30 male and 30 female) was used. The mean percentage of CD4+ T-lymphocytes was significantly decreased in T3N0M0 and T4N0M0 stages. In all TNM stages, especially in T3N0M0 and T4N0M0, the CD8+ T-lymphocyte subpopulation was significantly larger than in the control group. In all TNM stages the CD4+/CD8+ ratio was significantly lower than that of the control group. The degree of immune imbalance correlated directly with tumor size. The immunosuppression may be one factor in the development of BCC of the eyelid. Age- or genetic-related depression of cell-mediated immunity and increased exposure to carcinogenic agents, especially UV light, may play a part.

Antigen expression in canine tissues, recognized by a monoclonal antibody generated against canine melanoma cells.

A murine hybridoma monoclonal antibody (MAB), IBF9, was generated by fusing myeloma cells (P3X63Ag8.653) with spleen cells from a BALB/c mouse immunized with the canine melanoma cell line CML-10c7. Initial screening of hybridoma antibodies was performed by use of an indirect immunoperoxidase assay on formalin-fixed CML-10c7 cells. The isotype of MAB IBF9 was IgG1 as determined by radial gel immunodiffusion. The antibody was tested for reactivity against a panel of formalin-fixed, paraffin-embedded normal and neoplastic canine tissues, using immunoperoxidase staining. Immunostaining was observed in melanomas (24 of 38), a few carcinomas, basal cell tumors, and cutaneous lymphosarcomas. Immunostaining was not observed in fibrosarcomas, hemangiosarcomas, hemangiopericytomas, or histiocytomas. Staining of normal adult canine tissues was limited to a few epithelial tissues and a small percentage of lymphocytes. Fetal tissues were not reactive with MAB IBF9. There were statistically significant differences in frequency of reactivity among melanomas with regard to oral vs non-oral, malignant vs benign, and mitotic indices greater than or equal to 1 vs mitotic indices less than 1. Differences were not significant when tumors were compared for degree of pigmentation or histologic type. On the basis of these findings, we suggest that MAB IBF9 may be of assistance in diagnosis of nonpigmented melanomas and in assessing the malignant potential of melanomas.

Immunohistochemical staining of sebaceous cell carcinoma of the eyelid.

We characterized the inflammatory infiltrate of two sebaceous cell carcinomas of the eyelid with immunohistochemical staining to determine the functional class of the mononuclear cells associated with the tumor. The results were compared with the inflammatory infiltrate associated with basal cell carcinomas. The subepithelial spaces and the area immediately surrounding the sebaceous cell neoplasms were free of mononuclear inflammatory cells, in contrast to the basal cell tumors, which had large numbers of subepithelial inflammatory cells and inflammatory cells in intimate contact with the neoplastic cells as previously reported. Inflammatory reaction in the sebaceous cell tumor was limited to a T-cell infiltrate surrounding the vessels adjacent to the tumor. The predominant mononuclear inflammatory cell in both the sebaceous cell and the basal cell carcinomas was the T helper cell. The apparent difference in mononuclear cell infiltrate may be a significant factor in the clinical behavior of the tumors.

An overview of ocular adnexal lymphoid tumors.

In comparison with our earlier colleagues quoted in the introduction, we have made substantial progress in understanding the biology of ocular adnexal lymphoid tumors. While we have refined various categories with prognostic clinical value regarding possible associated systemic disease, none is foolproof and all have varying degrees of unpredictability. Comparatively well-differentiated histologic subtypes predominate among ocular adnexal lymphoid tumors. Polyclonal lesions occur less than half as often as monoclonal B-cell lesions. Molecular genetic studies have revealed small clones of monoclonal populations among the B-cells comprising most of the immunophenotypically polyclonal lesions, but no clonal genetic rearrangements have been uncovered within the preponderant constituent T-cell populations. The overall prognosis for ocular adnexal lymphoid tumors is excellent; when lumped together, 67% are not found to be associated with systemic disease with mean follow-ups of over 4 years. This is similar to experience with extranodal and extralymphatic lesions in other sites of the body, which also frequently have a small lymphocyte composition. The incidence of nonocular disease in all categories of our studies, however, will probably increase with the acquisition of longer follow-ups. Careful histopathologic evaluation is as good as immunophenotypic analysis of these lesions in predicting clinical outcome in terms of associated nonocular disease. Polyclonal and well-differentiated B-cell monoclonal lesions displayed equivalent clinical behavior. Benign polyclonal lesions may be associated with systemic disease but in a minority of cases (27%), as has also been determined in earlier studies. Clinical staging is the single most important predictor of associated monocular disease. In this study, patients with stage I-E disease had an 87% chance of not developing any nonocular lymphomatous lesion. We believe that this figure may also somewhat decrease with the passage of time. Precise anatomic localization of the lesion within the adnexa had considerable predictive value. Lesions of the conjunctiva fared the best; those of the orbit had an intermediate prognosis; while lid lesions had the worst prognosis. The most favorable prognosis would be held by a conjunctival lymphoid lesion in stage I-E composed of small lymphocytes. The fact that there is a fairly close equivalence in outcome between polyclonal and monoclonal well-differentiated lesions indicates that these lesions are in the vast majority of cases primary hyperplasias or primary lymphomas. The discovery by genetic probes of small monoclonal populations in immunophenotypically polyclonal lesions suggests that there is an evolution that goes on in situ.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical, morphologic, immunophenotypic, and molecular genetic analysis of bilateral ocular adnexal lymphoid neoplasms in 17 patients.

We investigated the clinical, morphologic, immunologic, and molecular genetic characteristics of the lymphoid tumors occurring in 17 patients with bilateral ocular adnexal lymphoid neoplasia. We found no obvious differences in the age, sex, clinical appearance, or ophthalmic findings between patients with unilateral and those with bilateral ocular adnexal lymphoid neoplasms. Five orbital and two conjunctival lymphoid neoplasms removed from five patients were polyclonal pseudolymphomas, while nine orbital, eight conjunctival, and two eyelid lymphoid neoplasms removed from 12 patients were monoclonal B cell non-Hodgkin's lymphomas. Each pair of simultaneously bilateral lesions occurring in a single individual was morphologically and immunologically identical and exhibited identical immunoglobulin gene DNA rearrangement patterns. None of the five patients with polyclonal pseudolymphomas developed nonocular non-Hodgkin's lymphoma, but one developed a contralateral conjunctival monoclonal B cell non-Hodgkin's lymphoma. Six of the 12 patients with ocular adnexal monoclonal B cell non-Hodgkin's lymphomas developed nonocular non-Hodgkin's lymphoma. The incidence of previous or subsequent systemic nonocular non-Hodgkin's lymphoma in patients with bilateral ocular adnexal lymphoid neoplasms is comparable to that of patients with unilateral disease. In both patient groups, the development of nonocular non-Hodgkin's lymphoma is most commonly associated with ocular adnexal lymphoid neoplasms displaying follicular or diffuse small cleaved cell (poorly differentiated lymphocytic) morphologic characteristics.