E. Scheffer

Dermatopathic lymphadenopathy and lymph node involvement in mycosis fungoides

Lymph node involvement in mycosis fungoides (MF) is associated with a poor prognosis. Histologically, in most cases of clinical lymphadenopathy the excised lymph node shows dermatopathic lymphadenopathy (DL). The diagnosis of MF involvement can readily be made when the lymph node tissue has partly or wholly been replaced by atypical lymphoreticular tissue. Early involvement of a dermatopathic lymph node by MF may be difficult to diagnose. A histologic study was performed on 30 lymph nodes from 24 patients with MF. Most of these lymph nodes had been excised as part of the staging procedure. The maximal follow‐up period was five years. A classification of lymph node involvement into four categories is suggested and correlations with clinical courses and results of DNA cytophotometry of lymph node imprints are shown. Lymph nodes showing the histologic picture of DL can be divided into two groups: a group without MF involvement (category I) and a group with MF involvement (category II). The latter group is considered to represent early involvement of lymph nodes by MF. Partial or complete replacement of lymph node tissue by atypical lymphoreticular tissue corresponds with categories III and IV, respectively.

Early diagnosis of mycosis fungoides and Sézary's syndrome by morphometric analysis of lymphoid cells in the skin

Mycosis fungoides (MF) and Sézarys syndrome (SS) are cutaneous T‐cell lymphomas characterized ultrastructurally by the presence of lymphoid cells with deep and narrow nuclear indentations (cerebri‐form mononuclear cells or CMC). Early diagnosis of MF and SS is difficult because in their early stages they often resemble various forms of chronic, benign skin lesions. By measuring the frequency distribution of a nuclear shape parameter (nuclear contour index or NCI) of lymphoid cells in skin infiltrates using computer assisted planimetry, we tried to classify suspect cases into the malignant and benign groups. From 12 patients with MF or SS (malignant group) and 11 patients with chronic, benign skin lesions (benign group) the frequency distribution of the NCI of the lymphoid cell population was measured. Nonlinear discriminant analysis selected the 70th and 25th percentile of the NCI distribution of the lymphoid cells in the skin infiltrates as parameters by which these patients could be classified correctly into the malignant or benign groups with a probability of over 95%. The predictive value of these parameters was tested on ten patients suspected of having cutaneous T‐cell lymphomas. Three cases were classified as benign and 7 as malignant. In a three‐year follow up cutaneous T‐cell lymphomas did not develop in any of the 3 cases classified as benign, MF developed in 5 of 7 cases classified as malignant, 1 patient has lymphomatoid papulosis and 1 patient is still suspect for MF. These results are compared with those of DNA cytophotometry performed on skin imprint preparations. It is concluded that morphometry of lymphoid cells in skin lesions of patients suspect for MF and SS can make an important contribution to an early diagnosis of MF or SS.

Cutaneous pseudo-T-cell lymphomas. A clinicopathologic study of 20 patients

The histologic features of 20 patients with cutaneous pseudo‐T‐cell lymphomas other than actinic reticuloid and lymphomatoid papulosis were investigated. Two histologic types of cutaneous pseudo‐T‐cell lymphomas were designated. The band‐like (MF‐like) pattern that simulated mycosis fungoides (MF) and a nodular pattern that mimicked cutaneous T‐cell lymphomas (CTCL) other than MF. Both patterns showed histologic features that generally are not found in CTCL and thus may be helpful in the differential diagnosis from CTCL. However, at present the differential diagnosis between pseudo‐T‐cell lymphomas and CTCL should be based on a combination of clinical and histologic data.

C-type virus-like particles specifically localized in Langerhans cells and related cells of skin and lymph nodes of patients with mycosis fungoides and Sezary's syndrome. A morphological and biochemical study.

SummaryC-type virus-like particles were found in 7 skin biopsies and in 4 lymph nodes from 7 patients with mycosis fungoides (MF). In addition, such particles were also found in skin biopsies from 2 patients with Sézary’s syndrome (SS). The particles were invariably found in cells derived from the mononuclear phagocytic series i.e. Langerhans cells and “related cells”, but never in cerebriform mononuclear cells (CMC) nor in any other cell-type. No virus-like particles were found in control specimens consisting of skin biopsies from 8 patients with chronic benign skin lesions and peripheral lymph nodes from 4 patients with unrelated diseases.In one patient with MF particles possessing some characteristics of retraviruses could be released from skin lesions. They band at a density of about 1.16 g/cm3 in a sucrose gradient and exhibit reverse transcriptase activity (RNA-dependent DNA-polymerase activity). Electron microscopy of the skin lesions and of the 1.16 g/cm3 sucrose gradient fraction confirmed the presence of C-type virus-like particles.The presence of C-type virus-like particles only in Langerhans cells and in related cells: i.e. indeterminate cells in the skin and IDC in lymph nodecells with a specific preference for T cell regions-from patients with MF and SS might be related to the aetiology of these cutaneous T cell lymphomas.

Immunohistochemical and histochemical tools in the diagnosis of amelanotic melanoma.

The histologic diagnosis of (metastatic) oligomelanotic or amelanotic melanoma may be difficult. In most cases this diagnosis can be established with conventional light and electron microscopic examination, supplemented with staining for melanin on ultrathin sections, but in other cases it remains equivocal. Therefore, the melanoma‐associated monoclonal antibody NKI/C‐3, effective on paraffin sections, was tested with an indirect immunoperoxidase technique. All 19 metastatic melanomas, used as positive controls, were stained. Seventeen of 23 primary melanomas and 8 of 9 initially equivocal eventually unequivocal melanomas (Group I) were stained with a diffuse cytoplasmic and in some cases locally peripheral pattern. Only two large cell undifferentiated carcinomas of 58 histogenetically unrelated but differential diagnostically relevant tumors showed localized staining in few tumor cells. Furthermore, 10 of 20 histogenetically related tumors (neuroendocrine tumors and clear cell sarcomas) were positive. These tumors however, can easily be differentiated from melanomas by other means. Of 15 equivocal melanomas (Group II) 9 cases reacted with NKI/C‐3, suggesting that it may be a useful marker for difficult metastatic tumors suspect for amelanotic melanoma. Although sensitivity of NKI/C‐3 for metastatic melanomas is high, its specificity is not sufficient. It therefore can be applied most properly in a selected panel of different tumor‐associated antibodies that are reactive in formaldehyde fixed, paraffin‐embedded tissue.

Melanocytic atypia in dysplastic nevi. Immunohistochemical and cytophotometrical analysis

In a double‐blind study a correlation was found between the histologically assessed degree of nevomelanocytic atypia in 58 dysplastic nevi (DN) and the presence of two markers associated with malignant transformation. The markers included a marked expression of histocompatibility locus Class I antigens on nevomelanocytes (P < 0.01) and abnormalities in the nuclear DNA content as measured by DNA cytophotometry (P = 0.01). Both markers were present in most of the markedly atypical DN, in about half of the moderately atypical DN, and in less than 30% of the mildly atypical DN. These findings suggest that a DN with marked or moderate melanocytic atypia indicates a premalignant condition and identifies a patient at risk for melanoma.

The prognostic value of membrane markers and morphometric characteristics of lymphoid cells in blood and lymph nodes from patients with mycosis fungoides

For 26 Patients With Mycosis Fungoides (Mf), The Type And Extent Of The Skin Lesions, The Percentage Of Cerebriform Mononuclear Cells (Cmc), And T And B Lymphocytes In The Peripheral Blood And Lymph Nodes Were Correlated With Mf Involvement Of Regional Lymph Nodes, The Clinical Course, And Response To Therapy. Skin Tumors And An Involvement Of More Than 25% Of The Skin Correlated Well With Lymph Node Involvement. Normal Percentages (2–18%) Of Cmc In The Peripheral Blood Were Found For Mf Patients Without Lymph Node Involvement When Compared With Those Found For Patients With Benign Erythroderma And Healthy Donors. Elevated Circulating Cmc Percentages (>20%) Were Observed In 9 Of 11 Mf Patients With Lymph Node Involvement. In The Lymph Node Cell Suspensions From Nine Of Ten Mf Patients With Lymph Node Involvement, Increased Cmc Values Were Found (>15%), Whereas Two Of Three Mf Patients Without Lymph Node Involvement Showed Percentages Comparable (4% And 7%, Respectively) With Those Of The Control Lymph Nodes. In The Peripheral Blood Of Patients With Mf, Decreased Percentages Of T Cells (≦55%) Were Found Predominantly For Patients With Lymph Node Involvement, Whereas Normal Percentages Were Noted For Most Of The Patients Without Lymph Node Involvement. No Consistent Differences In The Percentage Of T And B Cells In The Lymph Node Cell Suspensions Were Found Between Mf Patients With And Without Lymph Node Involvement. Patients With Lymph Node Involvement Showed In General A Partial Response To Therapy With An Unfavorable Clinical Course In Contrast To Patients Without Lymph Node Involvement. Increased Percentages Of Cmc (>20%) And Decreased Percentages Of T Cells (≦55%) In The Peripheral Blood, The Presence Of Skin Tumors, And Involvement Of More Than 25% Of The Skin Are Prognostically Unfavorable Signs For Patients With Mycosis Fungoides.

Lymphomatoid papulosis and Hodgkin's disease: Are they related?

SummaryTwo different characteristic types of lymphomatoid papulosis (type A and type B) can be histologically distinguished, that represent the ends of a spectrum. In the present report, two patients are described. One patient with both lymphomatoid papulosis type A and type B lesions for more than 25 years developed Hodgkins disease (nodular sclerosing type) in the para-aortic and para-iliac lymph nodes. Histologic examination of the skin lesions in the second patient, who had Hodgkins disease (nodular sclerosing type) in many supradiaphragmatic lymph nodes, showed the characteristic features of lymphomatoid papulosis type A. These findings, together with the results of recent immunohistochemical investigations showing many similarities between the large atypical cells in lymphomatoid papulosis type A lesions and Reed-Sternberg cells in Hodgkins disease, support the view that lymphomatoid papulosis type A and Hodgkins disease are closely related conditions. The results of recent studies indicate a close relationship between lymphomatoid papulosis type B and the early stages of mycosis fungoides. Accordingly, the possible relationship between lymphomatoid papulosis types A and B, mycosis fungoides, and Hodgkins disease is discussed.

A histologic study of lymph nodes from patients with the sézary syndrome

Lymph node sections from 12 patients with Sézary syndrome (SS) were studied histologically. The histopathologic alterations were compared with those in lymph nodes from four patients with (erythrodermatic) mycosis fungoides (MF) and two patients with a benign form of erythroderma. Most SS lymph nodes showed a rather monotonous and diffuse infiltration of cerebriform mononuclear cells (CMC), which tended to efface the normal lymph node architecture. By contrast, in lymph nodes involved by MF there was not only an increase in the number of CMC, but also a marked increase in the number of interdigitating reticulum cells that often showed a considerable degree of nuclear polymorphia. In the advanced stages of lymph node involvement by MF, blastic transformation was much more pronounced than in the SS lymph nodes. These histologic differences between MF and SS lymph nodes suggest that different pathogenetic mechanisms may be operative in the development of either of these conditions. Cancer 57:2375–2380, 1986.

Mycosis fungoides simulating acanthosis nigricans

In this paper, an unusual papillomatous variant of the plaque stage of mycosis fungoides with clinical similarities to acanthosis nigricans is described. In contrast to the classic plaque stage of mycosis fungoides, the dermal infiltrates in this patient showed a rather monomorphous proliferation of blast-like cells that had little or no tendency to infiltrate the epidermis.