Cases Of Primary Cutaneous Lymphoma Research Articles

Surgical, Dermatological and Morphopathological Considerations in the Diagnosis and Treatment of Cutaneous Lymphoproliferative Tumors, Primary CD4+

Primary cutaneous lymphomas are a heterogeneous group of T-cell (CTCL) and B-cell lymphomas (CBCL) developing in the skin and without signs of extracutaneous disease at the time of diagnosis. The term "primary small/medium CD4+ T-cell lymphoma" was changed to "primary small/medium cutaneous CD4+ lymphoproliferative disorder" due to its indolent clinical behavior and uncertain malignant potential. This paper presents a rare case of primary cutaneous lymphoma with small to medium CD4+ T-cells. A 37-year-old patient presented with a tumor in the frontal region that had occurred approximately 8-9 months earlier. The tumor had a diameter of about 8-9 mm, well demarcated macroscopically, it was round in shape, about 6-7 mm high, pink in color, firm in consistency and painless during palpation. Surgical excision of the tumor was performed with a margin of safety of 8 mm and deep to the level of the frontal muscle fascia. The histopathological examination supported the diagnosis of cutaneous lymphoproliferation with a nodular disposition in the reticular dermis and extension around the follicular epithelia and sweat glands, composed mainly of dispersed medium-large lymphocytes. Additional immunohistochemical examination was requested. Immunohistochemical examination confirmed the diagnosis of "primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder." Patient monitoring was carried out through clinical dermatological controls at 3, 6, and 12 months. After one year, a cranio-cerebral MRI was performed. For the following 5 years, an annual dermatological examination accompanied by cranio-cerebral MRI, blood count, and pulmonary X-ray were recommended. Similarly to all solitary skin lesions, the prognosis is excellent in this case, the only treatment being surgical excision.

Assessment of cases of primary cutaneous lymphomas- A clinical study

Background: Primary cutaneous lymphomas represent the second most common group of extranodal non-Hodgkin lymphoma after primary gastrointestinal lymphomas. The present study was conducted to assess cases of primary cutaneous lymphomas. Materials and methods: 82 cases of primary cutaneous lymphomas both genders were recruited. Duration of illness, presence of pruritus, family history, and occupational history was recorded. Results: Out of 82 patients, males were 48 and females were 34. Type of lesions were mycosis fungoides in 42, adult T-cell lymphoma/leukemia in 30 and peripheral T-cell lymphoma in 10 patients. Type of lesions were macules in 16, papules in 20, plaques in 22, macules & papules in 10, papules & plaques in 4, pustules and nodules in 6, plaques and nodules in 4 cases. The difference was significant (P< 0.05). Conclusion: Type of lesions were mycosis fungoides, adult T-cell lymphoma/leukemia and peripheral T-cell lymphoma in 10 patients. Type of lesions were macules, papules, plaques, macules & papules.

Diagnosis of gamma/delta mycosis fungoides requires longitudinal clinical observation

To the Editor: It is unclear whether epidermotropic cutaneous T cell lymphomas (CTCLs) exhibiting a T-cell receptor gamma delta (TCRγδ) phenotype initially presenting with patches and plaques should be considered a variant of mycosis fungoides (γδ-MF) or as primary cutaneous γδ T cell lymphomas (PCγδTCL).1Guitart J. Weisenburger D.D. Subtil A. et al.Cutaneous γδ T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas.Am J Surg Pathol. 2012; 36: 1656-1665Crossref PubMed Google Scholar, 2Merrill E.D. Agbay R. Miranda R.N. et al.Primary cutaneous T-cell lymphomas showing gamma-delta (γδ) phenotype and predominantly epidermotropic pattern are clinicopathologically distinct from classic primary cutaneous γδ T-cell lymphomas.Am J Surg Pathol. 2017; 41: 204-215Crossref PubMed Scopus (40) Google Scholar, 3Kempf W. Kazakov D.V. Scheidegger P.E. Schlaak M. Tantcheva-Poor I. Two cases of primary cutaneous lymphoma with a γ/δ+ phenotype and an indolent course: further evidence of heterogeneity of cutaneous γ/δ+ T-cell lymphomas.Am J Dermatopathol. 2014; 36: 570-577Crossref PubMed Scopus (22) Google Scholar Because PCγδTCL is considered an aggressive lymphoma,4Toro J.R. Liewehr D.J. Pabby N. et al.Gamma-delta T-cell phenotype is associated with significantly decreased survival in cutaneous T-cell lymphoma.Blood. 2003; 101: 3407-3412Crossref PubMed Scopus (229) Google Scholar the misclassification of epidermotropic PCγδTCL as MF may delay the decision to use systemic treatments. Our objective was to identify unique features that differentiate γδ-MF from epidermotropic PCγδTCL. We reviewed 4 patients (2 women and 2 men 39-71 years of age) from our cutaneous lymphoma clinic who presented with features resembling early-stage MF (stages IA-IB) and who had the TCRγδ phenotype. The clinical courses and histopathologic and immunophenotypic profiles of each patient are described in detail (Supplemental Tables I and II available via Mendeley at https://doi.org/10.17632/fhww2x8yy6.2). Cutaneous signs preceded the first diagnostic biopsy specimen by a median of 20 months (range 6-48 months), with a median follow-up of 64 months. Stage progression was noted in 3 patients, and 1 patient died. Besides case 1, all patients presented with patches and plaques on the distal extremities or the face rather than on sun-protected areas typical for MF. When disease progressed to tumors, the localization was atypical for classic MF (ie, the face and plantar aspects of the feet; Fig 1 and Supplemental Fig S1). Histologically, the infiltrate was indistinguishable from classic early-stage MF (Supplemental Figs S2 and S3). Immunophenotypically, cases demonstrated cytotoxic markers (granzyme B or T-cell intracellular antigen 1), a double-negative phenotype (CD4−/CD8−), an absence of TCR-βF1, positivity for TCRγδ, and monoclonal rearrangements of TCRγ genes. In all cases, Epstein–Barr virus–encoded small RNA in situ hybridization, peripheral blood flow cytometric analysis, and positron emission tomography–computed tomography scan for systemic involvement were negative. In cases 1 and 2, lymphoma was controlled by skin-directed therapies, while a combination of skin-directed and systemic therapies failed to control the aggressive disease in cases 3 and 4. An additional 29 similar cases were identified in the published literature (Supplemental Table III). Initial cutaneous lesions developed in non–sun exposed regions in approximately half of cases with a majority demonstrating a CD4−/CD8− double negative phenotype. There was an average survival of 107 months (8.9 years) from the onset of symptoms and an approximate average survival from the date of diagnosis of ≥26 months. Stage progression was noted in approximately 50% of patients, with 2 patients dying of disease. In conclusion, CTCLs clinically and histologically presenting as early-stage MF with a cytotoxic and γδ phenotype seem to have a more aggressive disease course compared with classic MF. We suggest reserving the diagnosis of γδ-MF only after an indolent clinical course is established. Patches and plaques beyond the bathing suit area, the atypical location of early tumors, γδ-phenotype, an aberrant immunophenotype (CD4−/CD8−, activated cytotoxic molecules), and early disease progression should prompt more aggressive clinical follow-up and the consideration of early systemic therapy because these patients are better diagnosed with primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma5Guitart J. Estela Martinez-Escala M. Subtil A. et al.Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.Mod Pathol. 2017; 30: 761-772Crossref PubMed Scopus (61) Google Scholar or epidermotropic PCγδTCL.

Skin Cancer: 13-Year Experience at the Department of Dermatology, Hospital Kuala Lumpur, Malaysia

Background: Unlike other types of cancers, skin cancer has received little attention in Malaysia, and there's little awareness of it among the public. According to the third report of the National Cancer Registry, Malaysia (2003-2005), skin cancer ranked the tenth most common cancer in Malaysia. Aim: The objective of this study was to determine the demography and the types of skin cancers seen in the Department of Dermatology, Hospital Kuala Lumpur. Methods: This was a 13-year retrospective review of all patients with skin cancers seen at the Department of Dermatology, Kuala Lumpur Hospital between 2005-2017. All patients confirmed to have skin cancer histologically were included in this study. Results: The total number of patients diagnosed to have skin cancer between the 13-year period was 426. The mean age of the patients was 59.5 ± 17.8. 56.1% of the patients were male and 43.9% were female. Majority of the patients were Chinese (46.2%), followed by Malay (34.3%), Indian (11.5%) and other ethnic groups (8.0%). The commonest type of skin cancer was basal cell carcinoma (31.9%), followed by cutaneous lymphoma (25.4%) and squamous cell carcinoma (24.2%). Malignant melanoma was not common and accounted for 5.6% of the patients. Other types of skin cancers such as cutaneous metastasis were seen in 4.5% of patients, extramammary Paget's disease in 4.2%, Kaposi sarcoma in 1.9% and other types of tumors accounted for 2.3% of the patients. Majority of the patients with primary cutaneous lymphomas were cutaneous T-cell lymphoma (CTCL), which accounted for 97.2% of all cases of primary cutaneous lymphomas. Conclusion: Basal cell carcinoma was the commonest skin cancer seen at the Department of Dermatology between 2005-2017. This is consistent with the reports from other parts of the world, which reported basal cell carcinoma as the commonest type of skin cancer.

Primary Cutaneous Lymphomas; A review of a rare but diverse cutaneous tumour

Title: Primary Cutaneous Lymphomas; University of Benin Teaching Hospital Experience Introduction: Primary cutaneous lymphomas (CLs) are a heterogeneous group of extra nodal non-Hodgkin lymphomas (NHL) which are confined to the skin at diagnosis. The skin is the second most common site of extra nodal lymphoma. They are rare tumours accounting for 18% of cases of extra nodal NHL. The goal of this study is to determine the prevalence of primary cutaneous lymphomas at the University of Benin, Teaching Hospital, Benin City, Edo State, Nigeria, vis-a-vis reviewing the existing literature on the subject matter. Methodology: A 10-year retrospective study of primary CLs seen in UBTH from January 2004- December 2013. Skin biopsies were received fixed in 10% formalin in the laboratory unit of the Department of Morbid Anatomy, UBTH, processed in paraffin wax, sectioned and stained with Haematoxylin and Eosin. Histology slides were retrieved, studied and lesions characterized. Result: There were 375 cases of histologically diagnosed cutaneous tumours. The ages of the patients in this study ranged from 1 to 111 years. Their mean age was 38.32 years (SD = 19.38. There were 192 females (51.2%) and 183 males (48.8%) giving a female to male ratio of 1.05:1. Keratinocytic tumours were the most common lesions seen. There was no case of primary cutaneous lymphoma seen in this study giving a prevalence of 0%. Discussion: Primary CLs are rare tumours. Previous studies in Nigeria and Ghana like the index study did not report a case of CLs. This is unlike the report from Lagos, Nigeria where CLs have been reported. So by extension, although CLs are rare we should not foreclose the possibility of finding isolated cases in our environment. Conclusion: We align with the submission of Bradford et al that further investigations using large populations and molecular tools are warranted to elucidate the aetiology of the diverse spectrum of CLs. Despite this, we trust without prejudice that case reports and institutional base studies as invaluable means in the gathering of data, especially for rare tumours like CLs.

Galectin-3 Expression in Primary Cutaneous CD30-Positive Lymphoproliferative Disorders and Transformed Mycosis Fungoides

Background: In nodal anaplastic large cell lymphoma, strong expression of galectin-3 (Gal-3) has been found, but only very few cases of primary cutaneous lymphoma have so far been examined. Objectives: To investigate 11 primary cutaneous anaplastic large cell lymphomas (PCALCL), 47 lymphomatoid papuloses (LYP) and 14 cases of transformed mycosis fungoides with CD30 expression (MF-T) for Gal-3 expression. Methods: A Gal-3 score was applied using a photo-based morphometric evaluation program. Double staining for CD30 and Gal-3 was performed. Furthermore, we recorded the cellular and extracellular sublocalization of the signal. Results: The Gal-3 expression in CD30+ tumor cells was significantly lower in MF-T in contrast to CD30+ lymphoproliferative disorders (CD30 LPD; p < 0.001), but we found no differences between PCALCL and LYP (p = 0.42). In PCALCL Gal-3 was more often localized in the cytoplasm in contrast to LYP, in which an equal distribution in the cytoplasm and the nucleus was more common (p = 0.9). Conclusions: The lower Gal-3 expression in MF-T in comparison to CD30 LPD might be an additional criterion to differentiate both entities. The different sublocalization of the Gal-3 signal might reflect a different biological function and behavior.

Two Cases of Primary Cutaneous Lymphoma With a γ/δ+ Phenotype and an Indolent Course

Cutaneous γ/δ+ T-cell lymphoma (CGD-TCL) is a rare but aggressive lymphoma associated with a poor prognosis in most patients. The clinicopathological spectrum is variable including predominantly epidermotropic infiltrates manifesting with patches and plaques or tumors with dermal and/or subcutaneous infiltrates. The diagnosis of CGD-TCL requires the demonstration of a γ/δ+ phenotype by immunohistochemistry. We report 2 patients with epidermotropic cutaneous T-cell lymphomas displaying a γ/δ+ phenotype, but exhibiting an indolent course. In one patient, the clinical presentation was similar to mycosis fungoides in patch and plaque stage, but recurrent blister formation within the lesions was observed accompanied by fever and arthralgias, whereas the second patient presented with 2 localized erosive plaques on the left temple and dense epidermotropic and dermal diffuse and folliculotropic infiltrates of atypical small-to-medium-sized lymphocytes. These cases corroborate the view that expression of a γ/δ+ phenotype in cutaneous T-cell lymphomas per se does not portend a worse prognosis and that CGD-TCL may represent a clinically and prognostically heterogeneous group.

Aggressive Behavior and Elevated Lactate Dehydrogenase at Baseline Confer Inferior Prognosis in Patients With Primary Cutaneous Lymphoma

Primary cutaneous lymphoma (PCL) comprises a heterogeneous group of diseases in regard to clinical presentation, histologic appearance, and biological behavior. Its rare occurrence limits analysis of disease features and survival of patients. All patients with PCL treated in our hospital during January 2006 to October 2012 were included in this retrospective study. Their histologic and clinical data were analyzed. The diagnosis of PCL and the evaluation of clinical behavior were based on the 2005 World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification. Fifty-four cases of PCL were included in the study. The median age was 52.5 years. Thirteen (24.1%) patients had B-cell lymphoma and 41 (75.9%) had T-cell lymphoma. Twenty-nine (53.7%) patients exhibited disease having indolent clinical behavior, 14 (25.9%) presented with B symptoms, and 16 (29.6%) had elevated lactate dehydrogenase (LDH) levels at baseline. Within a median follow-up of 47.8 months, the expected 5-year progression-free survival (PFS) rate and overall survival (OS) rate were 6% and 14%, respectively. Using multivariate analysis, aggressive behavior (hazard ratio [HR], 2.92; P = .01] and elevated LDH levels at baseline (HR, 2.88; P = .01) were identified as independent risk factors for PFS. In addition, aggressive behavior (HR, 4.09; P = .01) and elevated LDH levels at baseline (HR, 3.69; P = .01) were also identified as independent risk factors for OS. The study data suggest that aggressive behavior and elevated LDH levels at baseline were predictive factors for poor PFS and OS, which supports the need for immediate treatment of those patients.

Primary Cutaneous T-Cell Lymphoma Localized to the Lower Leg

Distinct categories of skin lymphoma with preferential site localization and unique clinical behavior, including leg-type primary cutaneous diffuse large B-cell lymphoma, have recently been described. Although these entities are rare, they exhibit reproducible clinicopathologic features, and their recognition may allow more appropriate treatment protocols. We describe the distinctive clinicopathologic features that were observed in 3 patients with an unusual variant of primary cutaneous T-cell lymphoma. All cases originated on the legs of elderly patients and exhibited a locally aggressive clinical behavior with relatively rapid relapses after radiotherapy and resistance to other therapies. Histologically, dense dermal-centered infiltrates of atypical, variably sized mature helper T cells were identified. One patient died of progressive disease. Rare cases of primary cutaneous lymphomas do not necessarily fit current criteria for a standard diagnostic category but may represent unique clinicopathologic entities, such as primary cutaneous T-cell lymphoma localized to the lower leg. It is important to be able to identify these unusual lymphoma variants for prognosis and adequate treatment. The aggressive nature of lymphomas preferentially localized on the lower extremities may not be restricted to B-cell or cytotoxic neoplasms.

Cutaneous diffuse large B‐cell lymphoma of the leg associated with chronic lymphedema

Development of malignant tumors is a rare but well known complication in chronic lymphedema (CL). We report herein a cutaneous diffuse large B-cell lymphoma of the leg associated with CL. An 89-year-old man presented with multiple cutaneous lesions on his right limb that showed a CL. Dermatological examination disclosed multiple violaceous, firm, slightly infiltrated nodules on the anterior aspect of the leg and the dorsum and sole of the foot. A biopsy of one nodule of the leg disclosed a diffuse large B-cell lymphoma, type of the legs. There was no evidence of lymphadenopathy on computed tomography (CT) scans of the chest, abdomen, and pelvis. A bone marrow aspiration and biopsy showed normal results. The patient was treated with local radiotherapy at a dose of 40 Gy, obtaining a highly significant, almost complete, clinical remission. A literature search identified 11 additional cases of primary cutaneous lymphoma associated with CL. An inadequate lymphatic drainage may make the lymphedematous region an immunologically vulnerable area, predisposing to neoplasia.

Staging and management of cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) accounts for two-thirds of cases of primary cutaneous lymphoma. Most variants of CTCL are indolent lymphoma, the most common being mycosis fungoides. In addition, Sézary syndrome, the leukaemic variant, has an aggressive clinical course. Accurate diagnosis and staging is critical in determining the prognosis of those with CTCL. The tumour, node, metastasis and blood stage needs to be documented and used to determine an overall stage from IA to IVB. Management of patients should be carried out by a multidisciplinary team. A full clinical examination should be made at all visits. Thorough investigations are needed at diagnosis and should be repeated during disease progression to allow initial staging and restaging. Treatment of patients with early-stage disease (IA-IIB) should be limited to skin-directed therapy. More advanced or resistant disease may be treated with systemic therapies such as extracorporeal photopheresis, immunotherapy, monoclonal antibody therapy, novel retinoids or chemotherapy, and where possible, patients should be entered into clinical trials.

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

Cutaneous B-cell lymphoma with subsequent laryngeal involvement

Cutaneous lymphoma is uncommon and lymphomatous infiltration of the larynx, occurring either as primary disease or as a feature of multifocal disease, is rare. We report a case of cutaneous, high grade non-Hodgkin's lymphoma with isolated relapse in the larynx. The laryngeal deposit was identical to the original cutaneous lymphoma, demonstrated histologically and using the polymerase chain reaction. Complete remission of the primary lesion was attained with local radiotherapy, and a second complete remission with chemotherapy. To date, no case of primary cutaneous lymphoma with subsequent involvement of the larynx has been reported, but the association is worth documenting, since symptoms referable to the larynx are easily overlooked. They may indicate incipient embarrassment of the airway, thus requiring urgent investigation and treatment, which is generally highly effective.