Primary Cutaneous CD30-Positive Anaplastic Large Cell Lymphoma in Childhood: Report of 4 Cases and Review of the Literature

Outcomes of primary cutaneous anaplastic large cell lymphoma across u.S. cancer care settings: A national cancer database analysis.

CD8-positive, CD30-positive cutaneous lymphoproliferative disorders constitute a rare subset of T-cell lymphoproliferative conditions, including variants of primary cutaneous anaplastic large cell lymphoma (ALCL), mycosis fungoides, lymphomatoid papulosis type D, cutaneous gamma-delta T-cell lymphoma and cutaneous peripheral T-cell lymphoma. These entities share overlapping clinical, histopathologic and immunophenotypic features, presenting both a clinical and pathological diagnostic challenge. Presented here is a 73-year-old man with a disseminated, indolent CD30+, CD8+ cutaneous lymphoproliferative disorder with overlapping clinical and histopathological features of both mycosis fungoides and primary cutaneous ALCL, as well as features of lymphomatoid papulosis. To our knowledge, this is the first case of a generalized CD8+, CD30+ eruption with features of both mycosis fungoides and primary cutaneous ALCL arising following an episode of solitary primary cutaneous CD8-positive ALCL.

Primary cutaneous lymphomas are a heterogeneous group of lymphoid malignancies, with approximately 65% originating from mature T lymphocytes (cutaneous T-cell lymphoma -CTCL), 25% from mature B cells (cutaneous B-cell lymphoma -CBCL), and the remainder from natural killer (NK) cells [1,2].Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare T-cell lymphoma affecting the skin, classified within primary cutaneous CD30+ lymphoproliferative disorders.It typically presents as chronic papular or ulcerative lesions, with no extracutaneous dissemination at the time of diagnosis.Histopathological assessment is crucial for the diagnosis [2].Immunophenotypic evaluation of abnormal cells helps to determine the lymphoma lineage belonging to T-cell or NK-cell.Additional investigations, including monoclonal antibody panels or molecular testing, may be needed in equivocal cases. objectIveThe aim of this publication is to present the case of primary cutaneous anaplastic large T-cell lymphoma, emphasizing current diagnostic and therapeutic management recommendations. AbstrActIntroduction: Anaplastic large cell lymphoma is a rare entity belonging to CD30+ lymphoproliferative disease classified as T-and NK-cell lymphoid disorders and neoplasms.Primary cutaneous lymphomas are confined to the skin, without involvement of lymph nodes or internal organs.Symptoms such as pruritus, fatigue, and cutaneous lesions are often misdiagnosed as allergic reactions or psoriasis.Objective: To present a case of primary cutaneous anaplastic large cell lymphoma and highlight the diagnostic challenges associated with this condition.Case report: A patient with long-standing cutaneous lesions, initially treated dermatologically, was referred to oncology clinic.Histopathological examination of the skin and lymph node biopsies confirmed the diagnosis of primary cutaneous CD30+ lymphoproliferative disorder clinically corresponding to anaplastic large cell lymphoma.Oncology--directed treatment was initiated.Conclusions: Cutaneous lymphomas are challenging to diagnose.Histopathological assessment is crucial for accurate identification.Early diagnosis and prompt treatment significantly improve prognosis.

An unusual case of cytotoxic peripheral T-cell lymphoma

The histological, immunophenotypic and clinical features of 19 primary cutaneous anaplastic large cell lymphomas (cutaneous ALCL) were compared with those of 18 primary nodal anaplastic large cell lymphomas (nodal ALCL) of T-cell or null cell type. Although cutaneous ALCL and nodal ALCL had identical morphological features, differences in surface marker expression and clinical behaviour were found. Immunophenotypical differences concerned the expression of epithelial membrane antigen (82% of the nodal ALCL were positive v. none of the cutaneous ALCL) and the cutaneous lymphocyte antigen (HECA-452), a possible skin-homing receptor on cutaneous T-lymphocytes (most tumour cells in 44% of cutaneous ALCL cases were positive, whereas nodal ALCL showed expression of HECA-452 on only few tumour cells (< 25%) in 18% of cases tested). Loss of T-cell markers was more pronounced for nodal ALCL. Patients with cutaneous ALCL were generally older (median 61 years) than patients with nodal ALCL (median 24 years) and, in contrast to the latter group, did not show bimodal age distribution. Survival after 4 years, using lymphoma-related death as an end-point, differed significantly between cutaneous ALCL and nodal ALCL; 92% for cutaneous ALCL and 65% for nodal ALCL (P = 0.04). The better survival of cutaneous ALCL patients could not be ascribed to differences in age, stage or initial mode of treatment. These data indicate that differences in immunophenotype and clinical behaviour exist between morphologically identical primary cutaneous and primary node-based ALCL. They indicate that the primary site is an important prognostic factor in predicting the clinical outcome of ALCL.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disorder that rarely occurs in children. Although there are currently no consensus guidelines for the treatment of cutaneous lymphoma in the pediatric population, the isolated form of PC-ALCL is typically managed by surgical excision or external beam radiation therapy. We report the case of a 6-year-old girl with primary cutaneous anaplastic large cell lymphoma that was treated with brachytherapy with no recurrence after 21months of follow-up, suggesting that brachytherapy may be considered as a treatment for pediatric cutaneous large cell anaplastic lymphoma.

Primary Cutaneous CD30 positive Anaplastic Large Cell Lymphoma (C-ALCL) is a non-Hodgkin lymphoma of cutaneous origin. It accounts for 12% of all cutaneous T cell lymphomas. The clinical manifestations of anaplastic large cell lymphoma can have various presentations. We describe a 24 years old man who presented with hypopigmented skin plaques with follicular prominence over anterior and posterior trunk for two years duration and erythematous skin nodules of face and right arm for eight months duration, showing histological features of CD30 positive Anaplastic Large Cell Lymphoma after repeated skin biopsies suggestive of cutaneous leishmaniasis.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is defined as anaplastic large cell lymphoma localized to the skin without extracutaneous involvement at the time of diagnosis. Histologically, PCALCL is characterized by a dense nodular infiltrate of large lymphocytes, extending into the deep dermis or subcutis. Epidermotropism is sometimes, but not frequently, seen. We herein report a case of PCALCL with prominent epidermotropism. A 63-year-old Japanese woman was referred to our hospital with a red nodule and indurated erythema in 1997. Histological findings of a skin biopsy specimen from a red nodule were typical of PCALCL, however, biopsy specimens from indurated erythema showed remarkable epidermotropism. Tumor cells were positive for CD4, and CD30, but negative for CD3 and CD8. She was diagnosed with PCALCL. In 2007, skin biopsy was performed again, which showed large atypical lymphocytes in the upper dermis with mild epidermotropism. Tumor cells expressed in both CC chemokine receptor 4 and CXC chemokine receptor 3, which may explain prominent epidermotropism in this case.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) differs from systemic anaplastic large cell lymphoma (sALCL) in cell biological behavior, clinical features, treatment, and outcome. PC-ALCL has been reported to rarely transition into sALCL, but the underlying mechanism is not clear. Here we report such a case with certain characteristics that shed light on this. Herein, we report a 43-year-old male with symptoms of a skin nodule and histologically confirmed PC-ALCL with high expression of Ki-67. After three months of observation, two skin nodules re-appeared with muscle layer involvement and was histologically confirmed as sALCL. Seventeen months after receiving six cycles of CHOP regimen, the patient had pain in the chest and back, cough, shortness of breath, and night sweats. This was confirmed as relapse of sALCL by immunohistochemistry and several organs, such as the lung were involved as shown by positron emission tomography/computed tomography. After four cycles of DICE plus chidamide regimens followed by auto-hematopoietic stem cell transplantation (ASCT), complete remission (CR) duration was achieved for twelve months while the patient was on maintenance with chidamide (20 mg) pills. This case had significantly high expression of Ki-67 when diagnosed as PC-ALCL initially and then transitioned into sALCL, which is rare. Auto-ASCT combined with demethylation drugs effectively maintained CR and prolonged progression free survival.

Simple SummaryPrimary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides. Although it usually presents as a localized nodule or papule (>2 cm), multifocal lesions may occur in some cases. Patients have an overall good prognosis either in localized or multifocal disease. Microscopically, this neoplasm consists of a dermal infiltrate of medium to large anaplastic cells that may extend to the subcutis. By immunohistochemistry, this tumor is strongly positive for CD30. Primary cutaneous ALCL can mimic several reactive skin conditions as well as other lymphoproliferative disorders, such as lymphomatoid papulosis, more aggressive primary cutaneous lymphomas, or systemic lymphomas involving the skin. Therefore, it is crucial to know the clinical presentation before establishing a diagnosis of primary cutaneous ALCL. Here, we review the clinical and histopathological features of primary cutaneous ALCL as well as its differential diagnosis and most common genetic alterations known to date.Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells.

Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a subtype of non-Hodgkin lymphoma (NHL) that is localized to the skin. Disseminated disease is rare, and visceral organ involvement is even more so. We report a unique case of PCALCL with gastric metastasis. A 75-year-old man with a history of cutaneous left lower extremity PCALCL status post radiation therapy initially presented with abdominal pain and was found to have diffuse celiac axis and retroperitoneal lymphadenopathy. Endoscopy, initially done to biopsy an involved lymph node (LN), demonstrated a friable gastric nodular lesion with telangiectasias. Biopsy of the lesion and LN revealed anaplastic large cell lymphoma, identical in pathology to the known skin lesion. The patient was treated with systemic chemotherapy with a good response. PCALCL has been thought of as a localized malignancy with a good prognosis and low potential for extracutaneous spread. To our knowledge, this is the first instance of metastatic PCALCL involving the stomach.

Anaplastic lymphoma kinase expression in a recurrent primary cutaneous anaplastic large cell lymphoma with eventual systemic involvement

A primary cutaneous CD-30 positive T -cell lymphoproliferative disorders are rare and heterogeneous group of primary skin tumors, which include primary cutaneous anaplastic large cell lymphoma (PCALCL) and lymphomatoid papulois. We report a rare an atypical case of PCALCL with an aggressive and refractory behavior that occurred in the lip vermilion, and that had been initially diagnosed as aggressive herpes. The lesion was recurrent and refractory to the CHOEP chemotherapy protocol followed by radiotherapy, but after hyper CVAD (acronym) + brentuximab with a considerable improvement. After 4 cycles of hyper CVAD plus brentuximab, the patient underwent 100% compatible sibling bone marrow transplantation, with success in the procedure. Primary cutaneous anaplastic large cell lymphoma is a rare disease of difficult diagnosis and may be confused with chronic infectious diseases, postponing treatment.

Primary Cutaneous Anaplastic Large Cell Lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disease of the skin characterized by single or focal nodules or plaques that ulcerate over time. Diagnosis of PC-ALCL relies heavily on clinicopathological correlations because of the potential morphological, clinical, and molecular overlap with other cutaneous CD30+ LPDs. Histopathologic features include diffuse nonepidermotropic infiltrates with an adherent layer of large undifferentiated CD30+ tumor cells. The Exact incidence of PC-ALCL is not known partially because of the difficulty differentiating from the variety of CD30+ Lymphoproliferative disorders. Only a few cases are reported even from developed countries &amp; reports from developing countries are lacking. We present a possible case of primary cutaneous Anaplastic Large cell Lymphoma in a 20 years old Female patient who presented with a 2 months history of lateral neck swelling.

Introduction:CD30+ primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a rare T-cell neoplasm, and has been reported to present with an indolent behavior. The PC-ALCL with aggressive behavior has not been reported in the literature.Patient concerns:We treated a patient with PC-ALCL that exhibited indolent behavior in the past 2 years and aggressive behavior within the last 3 months before presentation.Diagnosis:Aggressive CD30+ primary cutaneous anaplastic large cell lymphoma.Interventions:The radiotherapy regimen was individualized in terms of the target volume delineation and dose prescription, and the dose–response relationship was evaluated.Outcomes:The mean distance of microscopic infiltration was 14.1 mm in depth and 14.3 mm circumferentially. The lesion completely regressed after the delivery of 40 Gy in 20 fractions over 4 weeks. The tumor did not recur over the next year.Conclusion:An aggressive disease course is rare for indolent CD30+ PC-ALCL, which has similar histopathological characteristics as indolent PC-ALCL. The radiotherapy strategy should be individualized with curative intent.