Benign Lymphocytic Infiltrates Research Articles

Sicca to Lymphoma: Sjogren Syndrome

Sjogren Syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of exocrine glands. This abnormality leads to the destruction of these glands with the clinical expression of the sicca syndrome (dry eyes and dry mouth). Usually Sjogren Syndrome follows a non-aggressive course, but patients suffering from this disease have a very high risk of developing malignant lymphoma (MALT). The evolution from benign lymphocytic infiltration characteristic of Sjogren Syndrome to malignant lymphoma (usually MALT subtype) is a multistep process [1-3]. We present the case of 35 years old woman admitted to “Sf. Maria” Clinical Hospital—Bucharest, Romania, in the Rheumatology Department in May 2011, representative for the diagnosis difficulties as well as for the unfortunate evolution. She was diagnosed with primary Sjogren Syndrome in 2004. The first symptoms of the disease, dry eyes and dry mouth, appeared in 2000 but they were undermined by some hematological disorders, as the patient had a low white blood cell count at the biological evaluation. Four years later, when the diagnosis of Sjogren Syndrome was set, she already had some negative prognosis factors. In the end, the disease had an unfavorable outcome, as the patient developed non-Hodgkin malignant lymphoma for an unfortunate evolution.

The value of molecular diagnostics in primary cutaneous B-cell lymphomas in the context of clinical findings, histology, and immunohistochemistry

Primary cutaneous B-cell lymphoma (PCBCL) is classified into 3 major subtypes: primary cutaneous follicle center lymphoma (PCFCL); primary cutaneous marginal zone B-cell lymphoma (PCMZL); and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). Diagnosis of PCBCL is mainly based on clinical and (immuno)-histochemical grounds. We investigated the diagnostic value of the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol in PCBCL. We analyzed with the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol skin specimens from patients with well-defined clinical and (immuno)-histologic PCBCL (n = 18) in comparison with benign lymphocytic infiltrates (n = 9). For molecular staging we also investigated 13 extracutaneous samples from 6 patients with PCLBCL, LT. Each sample was investigated at least twice. Monoclonality was detected in all of 5 PCFCL; 5 of 6 PCMZL; all of 6 PCLBCL, LT; and 2 of 9 benign lymphocytic infiltrates. In 5 of 6 patients with PCLBCL, LT, a clone corresponding to the clone detected in the skin was detected in 3 of 5 bone-marrow, 4 of 5 blood, and 1 of 3 lymph node specimens. DNA amplification using tubes A and B of IgH was not possible in PCFCL/PCMZL, benign lymphocytic infiltrates, and extracutaneous specimens of PCLBCL, LT, even after repeated analysis up to 11 times. Pseudomonoclonality was identified by repeated analyses in one case of PCMZL and in one case of benign lymphocytic infiltrate. A multicentric, randomized, blinded study is necessary to confirm our results. Molecular diagnosis supports the clinical and (immuno)-histologic diagnosis in PCBCL. In PCLBCL, LT, molecular staging may be useful. Tubes C through E of IgH and Igκ analyses seem to be superior to tubes A and B of IgH. Each sample should be analyzed at least twice to assess the possibility of pseudomonoclonality.

Reassessment of diagnostic criteria in cutaneous lymphocytic infiltrates

Non-specific lymphocytic infiltrates of the skin pose difficulties in daily practice in pathology. There is still a lack of pathognomonic signs for the differential diagnosis between benign and malignant lymphocytic infiltrates. To evaluate the morphological and immunohistochemical profile of lymphocytic infiltrations of the skin according to clinical outcome. Retrospective; histopathological and immunohistochemical analysis. Referral center, university hospital. 28 cases of lymphocytic infiltrates of difficult differential diagnosis selected from the records. Eighteen histological variables and the immunophenotypic profile were assessed using the CD4, CD8, CD3, CD20 and CD30 lymphoid markers and compared to subsequent follow-up. The most common diagnoses were: initial mycosis fungoides (eight cases) and drug reactions (five cases). Single morphological variables did not discriminate between benign and malignant infiltrates except for the presence of Pautrier-Darier's microabscesses, which were found only in mycosis fungoides (p = 0.015). Patterns of superficial and deep infiltration (p = 0.037) and also the presence of eosinophils (p = 0.0207) were more frequently found in benign lymphocytic infiltrates. Immunohistochemical profile of T-cell subsets showed overlap between benign and malignant infiltrates with a predominance of CD4-positive (helper) lymphocytes in the majority of cases. A combination of clinical and histological features remains the most reliable approach for establishing a definite diagnosis in cases of lymphoid skin infiltrates.

Killer cell immunoglobulin-like receptor expression delineates in situ Sézary syndrome lymphocytes.

p140/KIR3DL2 has been identified in malignant cell lines isolated from the skin and blood of patients with transformed mycosis fungoides (MF) and Sézary's syndrome (SS). For the first time, the expression of a cell membrane structure appeared to be able to distinguish CD4+ tumour lymphocytes from reactive lymphocytes in these small cutaneous T-cell lymphomas (CTCLs). This study has examined the in vivo expression of this receptor in various CTCL subtypes, which constituted a heterogeneous group. Tumour cells diffusely expressed KIR in SS, in lymphomatoid papulosis (LyP) and in CD4+CD30+ as well as CD8+ large cell pleomorphic CTCL. In contrast, the infiltrating lymphocytes did not express KIR in MF at the patch/plaque stage or in CD4+CD30- large cell pleomorphic CTCL, except for scattered small cells. One quarter of the transformed MF tested exhibited KIR+ tumour cells, suggesting heterogeneity in this subtype. KIR expression was also examined in inflammatory lesions characterized by a dense infiltrate of T cells, such as lupus erythematosus and lichen planus. Only scattered CD8+ cells in lichen planus expressed a significant amount of KIR3DL2. Taken together, these results show for the first time that KIR molecules are expressed in distinct subtypes of malignant CTCL. It is also shown for the first time that SS and MF, which are frequent variants of CTCL with similar histological features, can be distinguished by their KIR3DL2 expression analysis. The identification of this KIR also differentiates between lupus erythematosus and lichen planus, which are both diseases with dense benign lymphocytic infiltrates.

The Clonal Nature of Pityriasis Lichenoides

Pityriasis lichenoides et varioliformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC) are benign lymphocytic infiltrates of the skin that classically present as either a recurrent papulonecrotic eruption (PLEVA) or a persistent, scaling, papular eruption (PLC). Observations of both types of lesions present on individual patients have led to speculation that both entities are related. Previous studies evaluating the DNA of biopsy specimens from patients with PLEVA and PLC revealed clonal T-cell receptor beta gene rearrangements. To analyze and compare the T-cell populations between lesions of PLEVA and PLC. Retrospective and prospective analysis of patient tissue samples, classified by histologic analysis. Extracted DNA from 13 skin biopsy specimens with the diagnosis of PLC and 14 skin biopsy specimens with the diagnosis of PLEVA was analyzed by polymerase chain reaction/denaturing gradient gel electrophoresis (PCR/DGGE). Molecular diagnostic laboratory at an academic medical center. Twenty-seven tissue samples were obtained from patients with a histologic diagnosis of PLEVA or PLC. These samples were analyzed by PCR/DGGE. The presence or absence of T-cell receptor gene rearrangements on PCR/DGGE analysis corresponding to a clonal population of T cells. Of 14 PLEVA specimens, 8 (57%) demonstrated monoclonal T-cell receptor gene rearrangements; 1 (8%) of 13 PLC specimens showed a gene rearrangement (P =.008, Fisher exact test). Our results demonstrate the polyclonal nature of the lymphocytic infiltrate found in almost all of the PLC specimens, which contrasts with the monoclonal nature found in most of the PLEVA specimens. These differences may represent different stages of the clinical evolution of a single entity that results from varying host immune responses to pathogenic factors. Specifically, we propose that PLEVA is a benign clonal T-cell disorder in which the clone arises from a subset of T cells in lesions of PLC. The host immune response to this clone determines the clinical and histologic findings in PLEVA.

The application of a pCR technique for the detection of immunoglobulin heavy chain gene rearrangements in fresh or paraffin-embedded skin tissue

Although detection of a clonal sequence of the heavy chain gene of immunoglobulin by the polymerase chain reaction (PCR) is frequently used to assess lymphoid infiltrates in skin biopsy specimens, there are no data on the sensitivity and specificity of this test in detecting clonal B cell populations. Having refined a PCR technique for the detection of immunoglobulin heavy chain (IgH) gene rearrangement in both fresh and formalin-fixed, paraffin-embedded skin samples, we undertook to define the role of this assay in the diagnostic setting. Thirty-one cases of cutaneous B cell lymphoma (CBCL), 19 cases of B cell pseudolymphoma (lymphocytoma cutis), 34 cases of benign lymphocytic infiltrates of the skin and one case of cutaneous T cell lymphoma (CTCL) were studied using the polymerase chain reaction assay. All biopsies were formalin-fixed, paraffin-embedded skin sections apart from 13 of the 31 CBCL specimens which were fresh skin specimens. DNA from the framework region 3 (FR3) sequence of the IgH genes was amplified to ascertain the presence of a clonal IgH gene rearrangement. The findings were correlated with histological and immunophenotyping results on all samples. The assay performed with 73% sensitivity and 100% specificity, comparable to results obtained examining fresh lymphoid tissue specimens from patients with B cell tumours. The results indicate that this technique is a useful tool in the work up of suspected CBCL and in differentiating between CBCL and mixed lymphocytic infiltrates, a clearly important distinction with regards to prognosis and treatment.

24 Detection of proliferative cell nuclear antigen (PCNA) is able to differentiate cutaneous malignant lymphoma and benign lymphocytic infiltration of the skin

24 Detection of proliferative cell nuclear antigen (PCNA) is able to differentiate cutaneous malignant lymphoma and benign lymphocytic infiltration of the skin

Childhood Jessner's lymphocytic infiltrate of the skin

We report a case of Jessner's lymphocytic infiltrate of the skin in an 11-year-old boy. This benign lymphocytic infiltrate was originally described in 1953, and classically occurs in middle-aged men. Its occurrence in children appears to be very rare, and there are only two other case reports in the literature.

Assessment of an anti-T-cell receptor variable region antibody panel in cutaneous T-cell lymphoma

Using a panel of seven commercially available monoclonal antibodies directed against specific sites of the T-cell receptor variable region, we have studied the staining patterns in 15 biopsies from 11 patients with cutaneous T-cell lymphoma (CTCL), and in five patients with benign lymphocytic infiltrates. Eight of the 11 patients with CTCL showed staining of the majority of lymphocytes with either V beta 8 alone (n = 3), V beta 12 alone (n = 2) or with both V beta 8 and V beta 12 (n = 3). None of the biopsies from patients with benign dermatoses showed staining of the majority of lymphocytes with any of the antibodies.

Benign lymphocytic infiltrate of the skin: correlation of clinical and pathologic findings.

In a retrospective study of 137 biopsy specimens of skin from 137 patients (69 men and 68 women) that had been obtained between 1972 and 1989 at our institution and that had perivascular and periappendageal lymphocytic infiltrates characteristic of those described as benign lymphocytic infiltrate (BLI), we determined the specificity of the histologic diagnosis and the correlation with clinical data. The final diagnoses, based on clinical and laboratory data and histologic findings, were BLI (59), possible BLI (7), lupus erythematosus (LE) (12), possible LE (7), procainamide-induced LE (1), insect bites (9), possible insect bites (3), polymorphous light eruption (4), lymphocytoma (4), urticaria (4), and indeterminate or miscellaneous diagnoses (27). BLI is a clinical and histologic syndrome that can be heterogeneous in origin. We recommend careful evaluation to exclude other disorders such as LE, polymorphous light eruption, lymphocytoma, and insect bites. Direct immunofluorescence microscopy and immunophenotypic studies may help distinguish BLI from LE.

The development of B-cell lymphoma in a patient with psoriasis treated with cyclosporine

A 67-year-old Nicaraguan man with a history of chronic, severe, recalcitrant psoriasis participated in a multicenter study investigating oral cyclosporine in the treatment of psoriasis. He received cyclosporine for approximately 8 months at doses of 5 mg/kg/day or less. Treatment with cyclosporine was eventually discontinued because of progressive nephrotoxicity. Approximately 7 months after the discontinuation of cyclosporine, the patient developed a mass in the left maxillary sinus extending to the orbit, the palate, and the infratemporal fossa. Pathologic and histochemical analysis of the mass revealed a B-cell lymphoma. The development of a benign lymphocytic infiltrate has been reported in a patient who received cyclosporine therapy for psoriasis; however, to the best of our knowledge, this is the first case in the United States of lymphoma developing in a patient who was treated with cyclosporine for a condition other than organ transplantation.

Polymerase chain reaction confirmation of Borrelia burgdorferi in benign lymphocytic infiltrate of dermis

Polymerase chain reaction confirmation of Borrelia burgdorferi in benign lymphocytic infiltrate of dermis

The many faces and phases of borreliosis II

Borrelia burgdorferi, the etiologic agent of Lyme disease, has also been associated with other cutaneous conditions. Acrodermatitis chronica atrophicans and lymphadenosis benigna cutis are also caused by B. burgdorferi. Recent evidence links some cases of progressive facial hemiatrophy of Parry-Romberg, benign lymphocytic infiltrate of the skin (Jessner-Kanof), lichen sclerosus et atrophicus, morphea, and Shulman syndrome with borreliae. This article reviews the manifestations of the diseases definitely linked to borreliosis and the evidence linking borreliae to progressive facial hemiatrophy, benign lymphocytic infiltrate, lichen sclerosus et atrophicus, morphea, and Shulman syndrome.

Benign lymphocytic infiltration (Jessner-Kanof): Another manifestation of borreliosis?

Benign lymphocytic infiltration (Jessner-Kanof): Another manifestation of borreliosis?

Rapid Occurrence of Nodular Cutaneous T-Lymphocyte Infiltrates With Cyclosporine Therapy

Cyclosporine, a potent immunosuppressive agent, has been successfully used in the treatment of several dermatologic conditions including psoriasis. However, the drug does have an array of toxic side effects that need to be carefully considered when determining the risk-benefit ratio for the treatment of skin disease. We present another potential adverse effect of cyclosporine, namely, a benign lymphocytic infiltrate. This eruption developed in a patient with psoriasis after only ten days of cyclosporine therapy. The exact mechanism by which cyclosporine induced the lymphocytic infiltrate is unknown, but it is postulated that cyclosporine caused an imbalance of T-cell regulatory systems, thus resulting in an expanded T-cell subpopulation and the clinical manifestation of erythematous papules and nodules.

Lymphocytic Surface Markers in Lymphoid Leukemoid Reactions

Although mononuclear cell surface markers are primarily used to determine the lineage and stage of differentiation of leukemias and lymphomas, they can also be helpful in discriminating between some cases of neoplastic and reactive conditions. Peripheral blood lymphocytosis secondary to infection most often shows increased numbers of activated T cells of the suppressor/cytotoxic subset. A few exceptions, such as in pertussis, show predominantly T-helper cells. Although persistent B-cell lymphocytosis is most often associated with neoplastic conditions, B-cell predominant reactive conditions may also occur. Lack of light chain restrictions on B-cell membranes suggests non-neoplastic disorders. Reactive lymphadenopathy most often shows a predominance of T cells with normal to increased T-helper/T-suppressor cell ratios. In addition, normal ratios of kappa/lambda light chain surface immunoglobulin usually occur on B cells of reactive lymph nodes. Benign lymphocytic infiltrates in skin most often show a predominance of activated T-helper cells. Distinguishing reactive from neoplastic dermal infiltrates by mononuclear cell markers can be extremely difficult and may require DNA genotypic analysis. Mononuclear cell markers applied to bone marrow in patients treated for leukemia and other disorders must also be interpreted with caution. The presence of CD10 antigen (CALLA) may herald recurrence of leukemia; however, this determinant is not leukemia-specific and may be found on normal cells. Similarly, lymphoid cells bearing TdT often represent recurrent leukemia, and they must be differentiated from immature nonmalignant TdT-positive cells. Immunologic surface markers must be interpreted together with a careful review of the morphology of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Sicca Complex and Infection With Human Immunodeficiency Virus

Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.

An Ultrastructural Morphometric and Immunohistochemical Analysis of Cutaneous Lymphomas and Benign Lymphocytic Infiltrates of Skin

Our combined ultrastructural, immunohistochemical, histologic, and clinical studies over the past five years have allowed us to compile diagnostic criteria useful in the evaluation of cutaneous lymphomas. As a group, mycosis fungoides (MF) patients could be distinguished from those with benign disorders of skin using ultrastructural morphometry (mean form factor and perimeter values), but with some overlap between groups. Another approach, the ultrastructural histogram method, however, clearly separated MF patients from patients with chronic dermatitis. Immunohistochemistry was useful in distinguishing cases of cutaneous peripheral T-cell lymphoma from MF cases on the basis of the occurrence of "novel phenotypes." Neoplastic T-cell infiltrates of skin can usually be distinguished from benign polyclonal T-cell infiltrates by the presence of one T-cell subset to the exclusion of others. Patients with convoluted B-cell lymphomas could also be distinguished from MF patients using ultrastructural morphometric dual parameter analysis. The diagnostic complexity of several cutaneous T-cell lymphoma cases is illustrated. We have emphasized in this study the strength of combining quantitative electron microscopy, immunohistochemistry, and histology in the diagnostic workup of cutaneous lymphomas. This integrative approach may be necessary to assure a definitive diagnosis in difficult cases.

An ultrastructural morphometric and immunohistochemical analysis of cutaneous lymphomas and benign lymphocytic infiltrates of skin. Useful criteria for diagnosis

• Our combined ultrastructural, immunohistochemical, histologic, and clinical studies over the past five years have allowed us to compile diagnostic criteria useful in the evaluation of cutaneous lymphomas. As a group, mycosis fungoides (MF) patients could be distinguished from those with benign disorders of skin using ultrastructural morphometry (mean form factor and perimeter values), but with some overlap between groups. Another approach, the ultrastructural histogram method, however, clearly separated MF patients from patients with chronic dermatitis. Immunohistochemistry was useful in distinguishing cases of cutaneous peripheral T-cell lymphoma from MF cases on the basis of the occurrence of "novel phenotypes." Neoplastic T-cell infiltrates of skin can usually be distinguished from benign polyclonal T-cell infiltrates by the presence of one T-cell subset to the exclusion of others. Patients with convoluted B-cell lymphomas could also be distinguished from MF patients using ultrastructural morphometric dual parameter analysis. The diagnostic complexity of several cutaneous T-cell lymphoma cases is illustrated. We have emphasized in this study the strength of combining quantitative electron microscopy, immunohistochemistry, and histology in the diagnostic workup of cutaneous lymphomas. This integrative approach may be necessary to assure a definitive diagnosis in difficult cases. (<i>Arch Dermatol</i>1986;122:1139-1154)

Single cell DNA measurements in benign cutaneous lymphoid infiltrates and in positive patch tests.

Cellular DNA in skin biopsies from eighteen patients with positive patch tests and eleven patients with benign lymphocytic skin infiltates (cutaneous lymphocytoma, lymphoplasia or Jessner's lymphotic infiltrate) was estimated by flow cytometry of propidium iodide-stained dermal cells. Specimens from three patients with patch tests and one with cutaneous lymphocytoma had DNA histograms similar to those of normal blood mononuclear cells. The remaining patients demonstrated DNA histogram abnormalities in the form of hyperdiploid peaks in forty-two of forty-five specimens. The estimated proportion of cells in the S-phase was similar in patch tests (median: 9.2%) and in benign lymphocytic skin infiltrates (median: 9.6%). The median number of cells in the G2/M-phase was 3.1% in both groups of disorders. These data indicate DNA content heterogeneity of the dermal cells in benign lymphocytic skin infiltrates. This may be attributed to DNA replication and/or chromatin dispersion during cellular activation and proliferation. The data also emphasize that hyperdiploid peaks are not necessarily indicative of the presence of separate cell clones.