Constant small-cell changes and variable LEF1 expression in DUSP22-rearranged primary cutaneous anaplastic large-cell lymphoma: Analysis of the repeated biopsies of three patients.

DUSP22-rearranged primary cutaneous anaplastic large-cell lymphoma (pcALCL) has a biphasic histological pattern defined by large dermal atypical lymphocytes and epidermotropic small lymphocytes resembling pagetoid reticulosis, but the positivity rate of the biphasic pattern in DUSP22-rearranged pcALCL is unknown. Immunohistochemically, LEF1 expression in >75% of tumor cells is associated with DUSP22-rearrangement (DUSP22-R) in systemic ALCL. However, whether this association applies to pcALCL remains unclear. To analyze these pathological clues for screening DUSP22-R, we reviewed 11 skin biopsies from three patients with DUSP22-rearranged pcALCL. All specimens showed a biphasic pattern, of which three showed nonpagetoid infiltration of the epidermis. In all lesions, small-cell changes of tumor cells were observed not only within the epidermis but also under the epidermis. LEF1 positivity rates varied by lesion (range: 30%-90%, mean: 59.6%) with only three patients expressing LEF1 in more than 75% of tumor cells. In conclusion, the biphasic pattern was a constant finding in DUSP22-rearranged pcALCL, but it was not always pagetoid reticulosis-like. The recognition of small-cell change outside the epidermis may be helpful in diagnosing DUSP22-rearranged pcALCL. However, LEF1 expression was variable and its diagnostic usefulness may be limited.

Pagetoid reticulosis in a 13-year old female. A unique immunohistochemical profile.

Pagetoid reticulosis (PR) is a rare lymphoproliferative disorder with indolent behavior considered a variant of mycosis fungoides. It is characterized by marked epidermotropism of the neoplastic lymphocytes. Since its original description, five cases have been reported in children. We report a new case of PR with an immunohistochemical profile not previously described in children.

Pseudocarcinomatous Hyperplasia, Squamous Cell Carcinoma, and Keratoacanthoma Associated to Lymphomas of the Skin and External Mucous Membranes: A Case Report and Literature Review.

Pseudocarcinomatous hyperplasia (PCH) is a benign reactive epithelial proliferation that may be associated to lymphomas of the skin or external mucous membranes. We present a case of single lesion mycosis fungoides (Woringer-Kollop's reticulosis pagetoid) associated with PCH that was initially misdiagnosed as squamous cell carcinoma (SCC) and review all PubMed-indexed previously reported cases on lymphomas of the skin or external mucous membranes associated to PCH, SCC, and keratoacanthomas. Including our own case, we collected data of 114 cases of cutaneous or mucosal lymphoproliferative disorders associated to PCH, 3 cases associated to SCC, and other 3 cases associated to keratoacanthomas. All cases were tabulated to the following parameters whenever data was available: sex, age, previous medical conditions, number of lesions (single × multiple), site of involvement (mucosa, skin or both), clinical impression, initial equivocal histopathologic diagnosis, final diagnosis, keratinocytic atypia (presence × absence), lymphocytic atypia (presence × absence), CD30-status, and treatment.

Dermoscopy of pagetoid reticulosis, with dermoscopic-pathologic correlation.

Pagetoid reticulosis (PR), also known as Woringer-Kolopp disease, is a rare variant of mycosis fungoides with distinctive clinicopathologic features. It clinically manifests as a solitary, erythematous, gradually enlarging, scaly, or verrucous plaque on the lower extremities, and due to its indolent course and nonspecific clinical features, may remain undiagnosed for years. In the current study, we describe the clinical and dermoscopic characteristics of a rare case of PR disease and correlate them with the corresponding histopathologic findings. Dermoscopy may prove beneficial in early diagnosis of this rare entity.

Woringer-Kolopp (Pagetoid Reticulosis) disease successful response to bexarotene gel.

Woringer-Kolopp (WK) is a rare subtype of cutaneous T-cell lymphoma (CTCL) with limited treatment options. Bexarotene gel is a topical retinoid used in the treatment of CTCL. This report describes three female patients (mean age 66 years) with WK disease who had an effective treatment response to bexarotene 1% gel. This treatment could provide a safe alternative to other current treatment modalities which have higher risks of potential adverse effects and lack of access to other conventional treatments such as light therapy.

Pagetoid reticulosis tumor cells with double expression of TCRγδ and TCRαß: an off-target phenomenon or genuine expression?

Pagetoid reticulosis (PR) is a low-grade primary cutaneous T-cell lymphoma showing localized patches or plaques with an intrapeidermal proliferation of neoplastic T-cells with heterogeneous immunophenotype. We describe a 73-year-old woman with a 8-year history of gluteal lesions of PR, whom large blast cells were CD4/CD8 double negative T-cells with an activated cytotoxic profile. The case was investigated using a broad panel of monoclonal antibodies including TCRγM1, a new available antibody that recognizes the γ chain subunit of the T-cell receptor (TCR) in formalin-fixed paraffin-embedded tissue. Large blast cells were simultaneously positive for TCRαß and TCRγδ with an activated cytotoxic phenotype. It is worldwide accepted the mutual exclusive expression of TCRαß and TCRγδ but six different studies, dealing with TCRγδ expression in various types of extra-nodal lymphomas, reported cases whom tumor cells expressed simultaneously TCRαß and TCRγδ. Our data and those of similar reports, suggest the possibility of existence of a subset of extra-nodal T-cell lymphomas showing simultaneous expression by tumor cells of TCRγδ and TCRαß with an immunoprofile consistent with an origin from TCRγδ+ T lymphocytes. This unusual subset has preferential, but not exclusive, skin localization and variable epidermotropism.

Localized pagetoid reticulosis (Woringer-Kolopp disease) completely response to NB-UVB combined with IFN.

A cutaneous lymphoproliferative disorder, localized pagetoid reticulosis (LPR), is rare but distinctive in its clinical and histopathological manifestations. Without an evidence-based medicine treatment guideline because of extremely low incidence, LPR poses a therapeutic challenge. We describe a 67-year-old Chinese woman with LRP who showed complete response to narrow-band ultraviolet B combined with intramuscular interferon alpha-2b.

Treatment of pagetoid reticulosis with intensity modulated radiation therapy.

Pagetoid reticulosis, also known as Woringer-Kolopp disease, is a rare variant of cutaneous T-cell lymphoma usually presenting as an isolated patch or plaque on the extremities. Immunohistochemical staining of T-cell markers can be variable, but as the name implies the epidermotropic lymphocytes consistently display a "pagetoid" appearance. The following case demonstrates clearance of this condition with intensity modulated radiation therapy, whereas most cases are managed with electron beam therapy if radiation therapy is implemented.

Woringer-Kolopp disease (localized pagetoid reticulosis): a systematic review.

OBJECTIVE: Woringer-Kolopp disease (WKD), also known as localized pagetoid reticulosis, is a rare variant of mycosis fungoides as described by the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification system for cutaneous lymphomas. Our objective was to conduct a comprehensive review that describes and evaluates patient demographics, clinical presentation, immunohistochemical findings, management, and outcomes of WKD. METHODS: The databases PubMed, Embase, and Cochrane Library were searched for relevant literature. Patient demographics, imaging, treatments, and other clinical characteristics were obtained. The literature search was conducted on December 7, 2020. Studies were included if they contained primary data related to WKD. Non-pertinent studies, non-English studies, non-human studies, review articles, or studies with insufficient case information were excluded. The quality of the included studies and the risk of bias were evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation Group (GRADE) criteria (2016), Oxford Centre for Evidence-Based Medicine: Levels of Evidence (OCEBM) (March 2009), and the Methodological Index for Non-Randomized Studies (MINORS) criteria (2003). RESULTS: A total of 84 studies with 143 patients met the inclusion criteria for this study. The most common chief complaint was an asymptomatic, slow-growing, and erythematous plaque. The average time from initial skin eruption to presentation was 97.6 months. Histologically, 128 cases of WKD displayed epidermotropism (97.7%). Various therapies, including radiotherapy, surgery, and local chemotherapy, were used. In total, 92 (78.6%) cases had complete remission and 11 (9.4%) cases recurred. CONCLUSIONS: WKD is a rare cutaneous T-cell lymphoma that often presents as a single plaque on the extremities with an indolent course and a favorable prognosis. However, it is often misdiagnosed, leading to delays in treatment. The diagnosis of WKD involves clinical appraisal, a biopsy of suspicious lesions, and immunohistochemistry. Monotherapy appears to be preferred compared to combination therapy for WKD with radiotherapy demonstrating among the highest cure rates and lowest recurrence. Future retrospective and prospective studies are needed to accurately determine the epidemiology, prognosis, and effective treatments for WKD. Limitations include a possibility of missed studies, heterogeneity in reporting methods, publication, and selection bias.

Pagetoid reticulosis in a prepubescent boy successfully treated with photodynamic therapy.

Pagetoid reticulosis or Woringer-Kolopp disease (WKD) is a rare variant of mycosis fungoides, consisting of localized patches or plaques containing intraepidermal proliferations of neoplastic T cells in a pagetoid distribution (similar to that of the adenocarcinomatous cells found in Paget disease of the nipple), which typically affects middle-aged and elderly men. We report a trial of photodynamic therapy (PDT) with topical aminolaevulinic acid (ALA), carried out on a 10-year-old boy with a solitary lesion of WKD on his foot, to avoid the long-term problems associated with the typical treatments for WKD of surgery and/or local irradiation. The plaque progressively flattened during treatment, and after nine PDT sessions over 13 months, the patient was clinically free of disease. PDT may be a viable alternative to surgery and local irradiation for localized cutaneous T-cell lymphoma, including WKD, especially in younger patients.

Woringer-Kolopp disease mimicking foot dermatitis.

Woringer-Kolopp disease, also known as localized pagetoid reticulosis, is a rare cutaneous lymphoproliferative disorder classified as a solitary variant of mycosis fungoides (MF). Despite the indolent and benign nature of the disease, misdiagnosis and inappropriate treatment may result in years of debilitating symptoms and even loss of function. We present the case of a patient with long-standing Woringer-Kolopp disease that mimicked foot dermatitis. Histopathologic examination demonstrated epidermotropic infiltration of atypical lymphocytes that were CD3+ CD4- CD8-. The patient was successfully treated with topical keratolytics and bexarotene gel 1% with minimal residual lesions after 8 years of follow-up. We discuss the characteristics of this rare disease in contrast with localized MF as well as more aggressive forms of epidermotropic T-cell lymphoma.

A case of pagetoid reticulosis treated with topical photodynamic therapy.

A 70-year-old male presented with reddish brown, keratotic plaque on his left leg which had grown slowly for ten years. The histopathological examination revealed acanthosis and bands of lymphocytes with significant epidermotropism. The intraepidermal lymphocytes showed large, pleomorphic and hyperchromatic nuclei with distinct nucleoli and perinuclear halos, positive for CD3, CD4 and CD30, negative for CD8, CD20 and high in Ki67 index. Accordingly, the diagnosis of Pagetoid reticulosis was made. The patient was then treated with topical photodynamic therapy once a week sequential to partial in-situ resection and preliminary skin dermabrasion and finally achieved complete remission without obvious scars or recurrence after four sessions.

CD4/CD8 double negative pagetoid reticulosis: a case report and literature review.

Pagetoid reticulosis is an indolent primary cutaneous T-cell lymphoma. It typically presents as a solitary and slowly growing patch or plaque on the extremity, histologically characterized by an acanthotic epidermis infiltrated with atypical lymphocytes. Here, we present histological, immunophenotypical and molecular findings of a 29-year-old Jamaican man with bilateral wrist plaques. Histology showed marked acanthosis, hyperkeratosis and an intraepidermal infiltration consisting of large atypical lymphocytes. Immunohistochemical stains showed CD3 and CD5 positive T cells with significant loss of CD7, double negative CD4 and CD8 and strong positive CD30. Molecular analysis showed a monoclonal T-cell receptor (TCR) gamma gene rearrangement. Review of the literature confirms that the immunophenotype of pagetoid reticulosis is variable with decreasing frequency of CD8+ cytotoxic/suppressor T cell, CD4+ helper T cell and least commonly CD4/CD8 double negative phenotypes. Although CD4/CD8 double negative phenotype appears to be associated with higher proliferation index, it does not appear to confer prognostic significance.

Pagetoid reticulosis after radiotherapy of primary cutaneous anaplastic large-cell lymphoma.

We describe a 60-year-old man with a history of primary cutaneous anaplastic large cell lymphoma on the chest, who presented with a new scaly red plaque on the same site 11 years after radiation therapy. Histological examination revealed a dense epidermotropic infiltrate of atypical mononuclear cells consistent with pagetoid reticulosis. Immunohistochemistry revealed the infiltrate to be CD4, CD8, and CD30. Remarkably, all the atypical cells were strongly CD30, and furthermore, the CD30 cells were found exclusively in the epidermis. In the initial cutaneous anaplastic large cell lymphoma lesion, the CD4, CD8, and focally CD30 atypical cells were well confined within the dermis with no epidermal component. To our knowledge, the present case seems to be the first description of pagetoid reticulosis presenting at the site of a previously treated dermal anaplastic large cell lymphoma. This case also represents an extreme presentation of epidermotropism and CD30 expression in pagetoid reticulosis.