Pagetoid Reticulosis Research Articles

Melanin Pigment Uptake Within Paget Cells

Background: The differential diagnosis of intraepidermal neoplasms showing cell clusters and/or single units with upward migration includes Pagets disease, melanoma in‐situ, Bowens disease, and Pagetoid reticulosis. Purpose: We describe three cases of Pagets disease of the nipple with melanin pigment uptake by Paget cells. Results: Clinical and pathologic material of three women with biopsy proven Pagets disease of the nipple was reviewed. Clinically, two cases demonstrated an excoriated nipple, one of which also showed a zone of depigmentation. The clinical appearance of the third case was not available. Histologically, each case demonstrated Paget cells singly and in clusters with cytoplasmic uptake of melanin pigment. Melanocytes were found in each case, but were neither increased in number nor showed atypical forms. The dendritic processes of melanocytes were found to encase single Paget cells. Pigment was also found dispersed in the papillary dermis and within melanophages. Conclusions: Melanin pigment uptake by Paget cells represents a significant potential pitfall in ultimately arriving at the correct diagnosis. Misdiagnosing these cases as a melanocytic lesion could potentially delay the management of an underlying breast cancer. Careful examination of melanocyte and melanin distribution with respect to Paget cells is warranted in such cases.

FC‐13 Molecular markers in canine T‐cell lymphoma

The objectives of this study were to review and correlate results of the clinical, histological and immunohistochemical features of different types of canine T‐cell lymphoma (CTCL) according to the World Health Organization Classification of 2002. Further, we intended to define criteria for the diagnosis of these distinct clinicopathologic entities and to determine the prevalence of molecular markers of therapeutic efficacy and thereby prognosis. Skin samples of 10 cases of cutaneous canine lymphoma were evaluated as follows: histological preparations utilizing H&E, immunohistochemistry for CD3 and CD79α, and retinoid acid receptors for RAR and RXR isomers. Results of these examinations were correlated with available clinical data. The diagnoses included: mycosis fungoides (five cases), pagetoid reticulosis (three cases), and nonepitheliotropic type (two cases). All cases were CD3+CD79α–, RARα+, RXRα+, RXRγ+; nine cases were RARβ+; and nine were RXRβ+. The presence of RARγ was not detected. CD3 positivity demonstrated T‐cell lineage. Differentiation of these three types of CTCL requires careful histological and cytological review as well as immunohistochemical evaluation. Clinically, nonepitheliotropic types often present with diffuse or multifocal cutaneous involvement; epitheliotropic types are less well defined and signs vary with stage of the disease. The presence of retinoid receptors suggests that, as in humans, the use of specific ligands may be effective in the treatment of canine cutaneous T‐cell lymphomas. Further updating of the World Health Organization system is required to better define the characteristic features of canine CTCL to permit more accurate diagnosis and prognosis, and thus effective treatment. Funding: Self‐funded.

Successful treatment of disseminated pagetoid reticulosis by oral PUVA therapy

Successful treatment of disseminated pagetoid reticulosis by oral PUVA therapy

Pagetoide Retikulose Typ Woringer-Kolopp

Die pagetoide Retikulose Woringer-Kolopp ist eine seltene Sonderform der kutanen T-Zell-Lymphome. Wir berichten über eine 77-jährige Patientin mit seit ca. 30 Jahren bestehender pagetoider Retikulose. Es wurde die Strahlentherapie durchgeführt. Auf Besonderheiten des Verlaufes und der Histologie wird hingewiesen.

Clinical and pathological spectrum of CD8-positive cutaneous T-cell lymphomas.

CD8+ T-cell lymphomas presenting in the skin are rare. We describe the clinical and histological features of 18 patients with CD8+ cutaneous T-cell tumors, which have been divided into four groups. Seven patients had precedent long histories of rashes, which progressively spread in a presentation similar to that of CD4+ mycosis fungoides (MF). Three patients had long-standing localized plaques consistent with a pagetoid reticulosis (PR) pattern. Two patients presented with erythroderma and had peripheral blood involvement consistent with a Sezary syndrome (SS) pattern and had rapidly progressive clinical courses. Six patients presented with cutaneous nodules of varying sizes and had variable outcomes, with two having rapidly progressive disease, two with indolent recurrences and a further two with complete responses to treatment. Histologically, 12 of the 18 cases showed an epidermotropic tumor infiltrate that was most marked in the three PR cases. Prominent periadnexal infiltration was seen in 11 cases. Similar to CD4+ MF, the skin-homing antigen, (cutaneous lymphocyte antigen: CLA), was strongly expressed in 13 of 16 tested cases. Expression of the cytotoxic granule protein granzyme B was noted in a majority of tumor cells in only three of 16 tested cases. We conclude that approximately half of CD8+ cutaneous T-cell lymphomas clinically and histologically resemble CD4+ MF/SS, whereas presentation as discrete nodular lesions are more common in CD8+ tumors as compared to those that express CD4.

Disseminated pagetoid reticulosis (Ketron-Goodman disease): Six-year follow-up

Pagetoid reticulosis consists of 2 types: Woringer-Kolopp and Ketron-Goodman disease (K-G). Compared with the former, K-G may have disseminated lesions and a guarded prognosis. We encountered a case of K-G in a 67-year-old man with disseminated plaques on the neck, the trunk, and both extremities. Histologic specimens demonstrated medium- to large-sized, atypical cells infiltrating in the lower epidermis. The phenotype (CD3+, CD4−, CD8−, CD45RO−, CD45RA+) and ultrastructural findings suggest that these cells were immature T cells. Although PUVA was initially effective, new plaques in which atypical cells are still present histologically, have appeared through a 6-year follow-up. Literature review revealed the high rate of recurrence. These findings suggest that K-G is an epidermotropic or immature T-cell variant of mycosis fungoides. In patients with K-G, therefore, long-term observation is necessary: Disappearance of cutaneous lesions may not mean cure. (J Am Acad Dermatol 2002;47:S183-6.)

Follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and Sézary syndrome.

Beginning in 1957, patients have been described with localized alopecia characterized histopathologically by mucin deposition within hair follicles (follicular mucinosis [FM]). At least 2 distinct diagnostic entities have been proposed: one occurring in children and young adults without association with other diseases ("idiopathic" FM), the other occurring in elderly patients and associated with mycosis fungoides or Sézary syndrome ("lymphoma-associated" FM). To determine whether idiopathic and lymphoma-associated FM are distinct or related entities. Case series. Department of Dermatology, University of Graz, Graz, Austria. Forty-four patients with FM were divided into 2 groups. Group 1 comprised 16 patients (mean age, 37.5 years) with no associated mycosis fungoides or Sézary syndrome; group 2 was made up of the other 28 (mean age, 52.2 years), who had clinicopathologic evidence of cutaneous T-cell lymphoma. Mean age was lower in patients with idiopathic FM, but a considerable overlapping among the 2 groups was present. Location on the head and neck region was common in both groups, but most patients with lymphoma-associated FM had lesions also on other body sites. In fact, solitary lesions at presentation were common in patients with idiopathic FM (11 [68.8%] of 16 patients), but uncommon in those with lymphoma-associated FM (2 [7.1%] of 28 patients). Histopathologic findings did not allow clear-cut differentiation of the 2 groups. Finally, a monoclonal rearrangement of the T-cell receptor gamma gene was demonstrated by polymerase chain reaction analysis in about 50% of tested cases from each group. Criteria previously reported to differentiate idiopathic from lymphoma-associated FM proved ineffective. In analogy to localized pagetoid reticulosis (Woringer-Kolopp disease), small-plaque parapsoriasis, and so-called solitary mycosis fungoides, idiopathic FM may represent a form of localized cutaneous T-cell lymphoma.

CD45RA+ immunophenotype in mycosis fungoides: clinical, histological and immunophenotypical features in 22 patients.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) usually characterized by a T-helper memory phenotype (CD3+, CD4+, CD8-, CD45R0+). Aberrant phenotypes are more commonly seen in the tumor stages. CD45RA expression has so far been documented in only a few cases of CD8+ or TCR gamma delta+ CTCL and in some pagetoid reticulosis cases. Two hundred and fifteen MF patients were immunophenotyped in our laboratory between January 1992 and June 2000 and 22 cases of CD45RA+ MF (8.7%) were identified by immunohistochemical analysis. The majority of these CD45RA+ patients (20/22) showed a patch-plaque stage disease and an indolent clinical course, as expected in early-stage MF. The remaining 2 patients presented with stage IIB and IVA MF, and were characterized by an aggressive clinical course, with systemic spread. The immunohistochemical analysis revealed that CD45RA+ neoplastic cells belonged to the memory compartment, displaying a CD62L-, CD11a+, CD29+ phenotype. Most patients showed aberrant phenotypes, with a loss of T-cell lineage markers and expression of cytotoxic molecules or gamma-delta chain of the T-cell receptor. Our data show that CD45RA+ MF is a rare variant of CTCL and shares with the classic MF cases both the clinical features and disease course, even if it is characterized by a higher incidence of immunopathological abnormalities.

Disseminated pagetoid reticulosis: plaques and tumoral lesions occurring simultaneously in the same patient

Disseminated pagetoid reticulosis is considered to have a poor prognosis. Some authors regard this disease as an epidermotropic type of mycosis fungoides rather than a distinct entity. We report the case of an 83-year-old woman with disseminated pagetoid reticulosis who subsequently developed tumoral lesions and died soon after the appearance of these tumours. Our case is in agreement with findings that disseminated pagetoid reticulosis has an aggressive clinical behaviour.

Mycosis fungoides: classic disease and variant presentations.

Mycosis fungoides is a peripheral non-Hodgkin's T-cell neoplastic process, representing the most common type of primary cutaneous malignant lymphoma. Neoplastic lesions classically show skin predilection and characteristic clinical and histologic features in patch, plaque, and tumor stages. In addition, several clinicopathologic variants of mycosis fungoides have been delineated, including poikiloderma atrophicans vasculare (parapsoriasis variegata), Sézary syndrome, granulomatous mycosis fungoides, hypopigmented mycosis fungoides, folliculocentric mycosis fungoides, syringotropic mycosis fungoides, and Woringer Kolopp disease. We will review the salient features of patch, plaque, and tumor stage mycosis fungoides in this article and follow with a discussion of these variant clinicopathologic presentations and of therapeutic modalities.

Mycosis fungoides with CD30-positive cells in the epidermis.

Large numbers of CD30-positive tumor cells are not typically observed in mycosis fungoides (MF), but CD30 expression may occur on large cells of MF that have transformed into high-grade large cell lymphoma. Of 202 patch/plaque phase MF cases studied by immunohistochemistry, we encountered 4 patients with patch-phase MF at stage Ia or Ib, whose lesions contained a high proportion (greater than 50%) of CD30-positive tumor cells within the epidermis. The morphologic and immunohistochemical features of these four cases were otherwise similar to those of other patch-phase MF cases, and were different from those of pagetoid reticulosis. More importantly, the clinical behavior of these cases did not differ from that of other cases of early MF without CD30 expression. The mechanism underlying the high levels of CD30 expression by epidermotropic tumor cells is unknown. With increased use of the CD30 immunohistochemical stain in the diagnosis of cutaneous lymphomas, similar cases are likely to be encountered, and perhaps will be evaluated for their clinical behavior.

Pagetoid Reticulosis (Woringer-Kolopp Disease): An Immunophenotypic, Molecular, and Clinicopathologic Study

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a form of cutaneous T-cell lymphoma that demonstrates striking epidermotropism on histologic examination. We present the histologic, immunologic, and molecular findings for seven patients who had PR. The patients ranged in age from 33 to 67 years. All patients presented with one or several thick plaques involving the distal extremities except for one patient, who presented with a tongue lesion. Immunohistochemical staining of the atypical lymphoid cells demonstrated a T-cell phenotype in all cases. In one of four frozen cases, the neoplastic cells were of T-helper cell phenotype (CD4 positive). Four of seven cases demonstrated a T-cytotoxic/suppressor cell phenotype (CD8 positive). The T-cell subset for the remaining two cases could not be determined. CD30 positivity and a high growth fraction as indicated by staining with Ki-67 were seen in three of seven and three of four cases, respectively. Genotypic analysis performed on three of our cases revealed T-cell receptor (γ and/or β) rearrangement, indicating a clonal proliferation. The clinical follow-up ranged from 15 months to 13 years. Four of seven patients are alive and free of disease after treatment with excision or local irradiation. One patient relapsed twice after treatment with radiation and photochemotherapy with 8-methoxypsoralen and UVA and was then lost to follow-up. The lesions of another patient resolved spontaneously but recurred at the same and in an additional site 5 years later. One patient recurred after electron beam therapy. The recurrent lesion improved with radiation therapy and local wound care but never resolved completely. The patient died of unrelated causes. Our findings suggest that PR is a distinct clinicopathologic entity, separate from unilesional mycosis fungoides, demonstrating a slow disease course. The disease is a clonal cutaneous T-cell lymphoma with relatively consistent clinical and histopathologic findings but a heterogeneous immunophenotypic profile.

Unilesional Mycosis fungoides

Background: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized by a solitary lesion clinically and by histopathological features indistinguishable from those of MF, and typically having a benign course. Objective: To describe the clinicopathological features of a series of patients with unilesional MF. Methods: The records of cases of unilesional MF identified during a 10-year period in two medical departments were reviewed. Results: There were 7 patients: 6 males, 1 female; mean age at the time of diagnosis: 32 years; age range: 12–58 years; 3 were below the age of 18 years. The mean pretherapy follow-up period was 9 years (range: 2–20 years). In 5 patients, the eruption consisted of a characteristic patch or plaque of MF located on the trunk or upper extremity; in 2 it was atypical – in 1, a hypopigmented patch, and in 1, a plaque indistinguishable from MF-associated follicular mucinosis. Histopathologically all the lesions exhibited features characteristic of MF, with CD3+ lymphoid cells. In 6 cases (with available fresh frozen tissue) there was a predominance of CD3+ CD4+ cells; in 1 of 5 there was deletion of CD7, and in 3 of 5 there was an overexpression of IL-2 receptor. T-cell receptor γ gene rearrangement was found in 1 of 4 cutaneous lesions tested; in 2 cases it was found in the blood but not in the skin. Treatment modalities included localized electron beam, excision, topical nitrogen mustard or topical steroids and sunbathing, resulting in all cases in a sustained complete clinical response. In 1 patient, however, there were 2 local recurrences and in yet another patient there was distant cutaneous spread 3.5 years after therapy. Conclusions: Unilesional MF is a rare variant of CTCL, has heterogeneous clinical manifestations and can affect any age group, including children. The histopathological and immunophenotypical features are in general indistinguishable from those observed in multilesional MF. Although it is a unifocal event, there may occasionally be cutaneous spread with the appearance of noncontiguous lesions, even a long time after therapy. Whether all cases represent minimal-stage IA MF or whether some are actually T-cell pseudolymphoma remains to be clarified.

Solitary skin lesions with histopathologic features of early mycosis fungoides.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually begins with cutaneous patches that evolve into plaques and tumors. A few recent reports describe a solitary variant of MF distinct from localized pagetoid reticulosis, a disease in which solitary verrucous lesions occur on acral skin. Solitary skin lesions with some of the histopathologic features of MF rarely occur during treatment with several drugs, especially antidepressants or antihistamines. We analyzed the clinicopathologic features of 20 patients with solitary skin lesions showing histopathologic features of patch- or early plaque-stage MF. Eight men and 12 women (mean age 50.6, range 23-82, median 49) had solitary, small erythematous patches or plaques located on the trunk (16 cases, 6 of them on the breast), upper extremities (3 cases), and inguinal region (1 case). Ten patients were treated with one or more drugs; only two of them received antidepressants or antihistamines. Histopathologic examination revealed in all cases a band-like infiltrate in the upper dermis, frequently with epidermotropism of solitary lymphocytes. Atypical lymphocytes were present in a minority of cases. Immunohistology showed a predominance of CD3+ T lymphocytes, in most cases admixed with clusters of CD20+ B-cells. Only a small proportion of the infiltrate was CD8+. Molecular analysis of the rearrangement of the T-cell receptor genes was performed in 16 cases using the polymerase chain reaction (PCR) technique and revealed a monoclonal band in 8 of them. After surgical excision, 2/14 patients had a recurrence near the surgical scar. In 18 patients with complete follow-up data, no evidence of "classic" MF could be observed after a mean follow-up of 31.9 months. Solitary skin lesions with the histopathologic features of MF can be considered as a distinct clinicopathologic entity, probably representing a solitary variant of mycosis fungoides.

Primary Cutaneous CD8-Positive Epidermotropic Cytotoxic T Cell Lymphomas: A Distinct Clinicopathological Entity with an Aggressive Clinical Behavior

Cutaneous T cell lymphomas (CTCL) generally have the phenotype of CD3+, CD4+, CD45RO+ memory T cells. CTCL expressing a CD8+ T cell phenotype are extremely rare and ill-defined. To elucidate whether these CD8+ CTCL represent a distinct disease entity, the clinical, histological, and immunophenotypical features of 17 CD8+ CTCL were reviewed. None of the 17 cases expressed markers characteristic of natural killer cells or gamma/delta T cells. Nine of 17 cases showed the characteristic clinical and histological features as well as clinical behavior of well defined types of CTCL, such as mycosis fungoides (2 cases), pagetoid reticulosis (2 cases), lymphomatoid papulosis (2 cases), and CD30+ large T cell lymphoma (2 cases), all of which usually express a CD4+ T cell phenotype, and 1 case of subcutaneous panniculitis-like T cell lymphoma. The other 8 cases formed a homogeneous group showing a distinctive set of clinicopathological and immunophenotypical features, not consistent with that of other well defined types of CTCL. Clinical characteristics included presentation with generalized patches, plaques, papulonodules, and tumors mimicking disseminated pagetoid reticulosis; metastatic spread to unusual sites, such as the lung, testis, central nervous system, and oral cavity, but not to the lymph nodes; and an aggressive course (median survival, 32 months). Histologically, these lymphomas were characterized by band-like infiltrates consisting of pleomorphic T cells or immunoblasts, showing a diffuse infiltration of an acanthotic epidermis with variable degrees of spongiosis, intraepidermal blistering, and necrosis. The neoplastic cells showed a high Ki-67 proliferation index and expression of CD3, CD8, CD7, CD45RA, betaF1, and TIA-1 markers, whereas CD2 and CD5 were frequently lost. Expression of TIA-1 pointed out that these lymphomas are derived from a cytotoxic T cell subset. The results of this and other studies reviewed herein suggest that these strongly epidermotropic primary cutaneous CD8+ cytotoxic T cell lymphomas represent a distinct type of CTCL with an aggressive clinical behavior.

Role of superantigens in dermatology.

Superantigens are very potent agonists of T-lymphocytes. The superantigenic types of reactions on various subsets of T-lymphocytes are compared with those of classical antigens and aspecific mitogens. The role they could play in skin disease is reviewed with special emphasis to acute and chronic diseases, auto-immunity, immediate type reactions, immunodeficiency, carcinogenesis, psoriasis and other inflammatory cutaneous conditions.

Radiotherapy for unilesional mycosis fungoides

Purpose: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975.Methods and Materials: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation.Results: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%.Conclusion: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Mycosis fungoides granulomatous

We present a rare case of pagetoid reticulosis arising in a 5-year-old white boy. He had a history of a large chronic erythematous, scaly patch on his left buttock that had shown intermittent partial response to a topical antifungal medication. A punch biopsy specimen revealed dramatic epidermal hyperplasia, with parakeratosis and prominent exocytosis of single and clustered mononuclear cells (Pautrier's microabscesses) into the epidermis. Some of these exhibited hyperchromatic nuclei with irregular contours. They stained prominently for CD3, CD4, and CD8, with a predominance of CD8+ cells. T-cell receptor gene rearrangement by polymerase chain reaction was negative for a clonal process on a second biopsy specimen that was nondiagnostic on routine sections. Pagetoid reticulosis is an indolent, unilesional variant of mycosis fungoides, in which the atypical T cells may express a CD4−/CD8+ phenotype. This is in contrast to primary cutaneous epidermotropic CD8+ cytotoxic T-cell lymphoma, which is often very aggressive with a poor outcome. Pagetoid reticulosis is exceedingly rare in children and adolescents. Two features predict a benign course in this 5-year-old child: the unilesional clinical presentation and the CD8 predominance of the epidermal lymphocytes.

A clinical report of disseminated form of pagetoid reticulosis

A clinical report of disseminated form of pagetoid reticulosis

Unilesional Mycosis Fungoides or Lymphomatoid Keratosis?

I read with interest in a recent issue of theArchivesthe "Off-Center Fold" case report by Evans et al¹of an asymptomatic scaly plaque measuring 1.1×1.5 cm, which showed histological features of mycosis fungoides (MF) and was interpreted as an example of unilesional MF. Mycosis fungoides has received a great deal of public exposure in Australia with the death of Paul Eddington, the British actor, and more recently the public struggle of a patient with advanced MF who elected to undergo voluntary euthanasia under the recent controversial legislation passed in the Australian Northern Territory. The public perception of MF is that of a terminal disease. I recall being sent for review the histopathologic material of 3 patients who underwent excision biopsies of solitary lesions measuring 1 to 2 cm in diameter that were associated with a short history of change and pruritus. While the histopathologic material on the