A review of the solitary cutaneous T‐cell lymphomas

Cutaneous T‐cell lymphomas (CTCL) account for almost 65‐92% of all cutaneous lymphomas, many of which usually present with multiple lesions. However, a number of well‐recognized and rare types of CTCL, including mycosis fungoides, can present in isolated fashion. These solitary lesions often run a relatively indolent clinical course but often pose diagnostic difficulties. We review histopathologically challenging solitary cutaneous T‐cell lymphomas, including criteria for diagnosis, clinical course and prognosis, particularly for primary cutaneous CD4+ small/medium pleomorphic lymphoma and indolent CD8+ lymphoid proliferation of acral sites. In addition, we suggest an algorithm and nomenclature to aid in the diagnosis of such problematic lesions.     

Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma with a chronic and indolent course. Is this different from peripheral T cell lymphoma?

Cutaneous T cell lymphomas most commonly have a CD4+ memory T cell phenotype and exhibit a relatively indolent course, but may in rare cases present with a CD8+ cytotoxic phenotype with a strikingly more aggressive clinical behavior. Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma is an extremely rare entity with distinct clinicopatological features. The clinical features and prognosis of the recently-described CD8+ peripheral lymphoma are very different from cytotoxic CD8+ epidermotropic lymphoma, but the histological and phenotypic characteristics are very similar. We report a new case of CD8+ epidermotropic lymphoma with a chronic course and suggest the possibility of an overlap between these two types of lymphoma.     

Primary cutaneous CD4 positive small/medium T‐cell lymphoma with high proliferation index and CD30‐positive large lymphoid cells

Primary cutaneous CD4 positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) represents a provisional subtype of primary cutaneous T‐cell lymphoma with indolent clinical course. A few aggressive fatal cases with increased proliferation rate and few infiltrating CD8 positive T‐cells have been reported. We describe a case of SMPTCL with an increased proliferation rate, admixed CD30‐positive large lymphoid cells, and few infiltrating CD8 positive T‐cells. The lymphoma cells were positive for CD3, CD4, CD2 and CD5, and negative for CD8. A subset of the lymphoma cells was positive for follicular helper T‐cell markers bcl‐6 and PD‐1. There were approximately 20% CD30‐positive large lymphoid cells, and Ki‐67 showed a moderately high proliferation rate (～40%), mostly in the large lymphoid cells. CD8 infiltrating T‐cells were few (<5%). The patient had an indolent disease with complete response to radiation therapy. To the best of our knowledge, this is the first reported case of SMPTCL with an increased proliferation rate and large CD30+ cells that followed an indolent clinical course.     

Primary cutaneous acral CD8 positive T‐cell lymphoma with extra‐cutaneous involvement: A long‐standing case with an unexpected progression

Primary cutaneous acral CD8+ T‐cell lymphoma (acral CD8+ TCL) is a new provisional entity characterized by acral skin lesions and an indolent course. We describe an extraordinary case characterized by relapsed nodules with CD8+ cytotoxic infiltrates on the left ear. After 35 years, the skin lesions spread to other acral sites, and a mass with the same histological features as the other skin lesions appeared on the nose. Multiple courses of chemotherapy led to stable disease. Histological examinations carried out at different times showed the gradual transformation of the neoplastic cells, with an increased proliferation index. Genomic analysis revealed losses in the regions harboring the genes involved in cell cycle control. This is the first case of an acral CD8+ TCL with a very long history of indolent nodular lesions progressing to extra‐cutaneous sites.     

Indolent CD8+ lymphoid proliferation of the ear: report of two cases and review of the literature

Indolent CD8+ lymphoid proliferation of the ear is a recently described cutaneous lymphoid proliferation that clinically presents with slow growing lesion(s) on the ear(s). In cases reported to date, there has been indolent clinical behavior and no evidence of systemic involvement. Characteristic histopathologic features include a non-epidermotropic diffuse dermal infiltrate of CD8+ T-lymphocytes with a lymphoblast-like appearance. T-cell clonality has also been observed. Herein, we present two patients who show clinical, histopathologic and immunophenotypic features similar to the original index cases described by Petrella et al. In addition, we review the literature regarding this unusual lymphoid proliferation and provide evidence that this entity represents a phenotypic variant of primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, a concept proposed by Beltraminelli et al. in 2009. Differentiation between this lymphoproliferative process and other more aggressive CD8+ lymphomas is essential in avoiding excessive treatment of a condition that combines worrisome histopathology with indolent clinical behavior.     

Indolent CD8‐positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small‐/medium‐sized pleomorphic T‐cell lymphoma or a distinct entity?

We report two cases of a CD8‐positive lymphoid proliferation presenting as solitary lesions on the ear and nose, respectively. Histopathologically, both cases were characterized by a diffuse non‐epidermotropic dermal proliferation of clonal medium‐sized CD8‐positive T‐lymphocytes with a lymphoblast‐like appearance, having cells with large folded nuclei, prominent nucleoli and ample amphophilic or pale eosinophilic cytoplasm. Staging procedures excluded systemic involvement, and both lesions were successfully treated with localised radiotherapy without evidence of recurrence after 12 and 24 months' follow up, respectively. Previously reported cases on the ear had similar clinicopathological and immunophenotypical features, and together raise the possibility of a distinct entity, an indolent CD8‐positive lymphoid proliferation. Suchak R, O'ConnorS, McNamara C, Robson A. Indolent CD8‐positive lymphoid proliferation on the face: part of the spectrum of primary cutaneous small‐/medium‐sized pleomorphic T‐cell lymphoma or a distinct entity?     

Primary cutaneous acral CD8+ T‐cell lymphoma of the ear: A case report

Primary cutaneous acral CD8+ T‐cell lymphoma (TCL) is a rare, distinct type of cutaneous TCL. Despite its worrisome histological appearance it has a benign clinical course. It is therefore important to recognize this as a distinct entity from other more aggressive CD8+ lymphomas, for which the management is very different.     

Cutaneous CD8+ squamous T-cell bullous lymphoma

INTRODUCTION: Bullous forms of cutaneous T-cell lymphomas are rare. A new group of cutaneous T-cell lymphomas has recently been identified as a distinct clinicopathological and immunophenotype entity. These cutaneous T-cell lymphomas express a CD8+ phenotype, rarely expressed in other cutaneous T-cell lymphomas. CASE REPORT: We describe a cutaneous CD8+ squamous T-cell lymphoma with polymorphic clinical features, strongly epidermotropic lymphoid infiltrate and spongiosis, classical for this type of lymphoma. DISCUSSION: Bullous lesions in cutaneous T-cell lymphoma should evoke the possibility of a cutaneous CD8+ T-cell lymphoma, once other bullous diseases have been excluded. Spongiosis, rare in other types of T-cell lymphoma, and strongly epidermotropic pleomorphic lymphoid infiltrate are classical histological features. The association of polymorphic lesions, bullas and atypical CD8+ epidermotropic phenotype should evoke this diagnosis even at the early stage. Treatment is difficult and classical chemotherapy often fails. Prognosis is poor with a mean overall survival of 32 months.     

Childhood mycosis fungoides with a CD8+ CD56+ cytotoxic immunophenotype

Primary cutaneous T‐cell lymphomas mostly occur in patients of middle and higher age. Their rarity and an oftentimes atypical clinical presentation in childhood as well as the reluctance of taking biopsies in children are reasons for a delayed diagnosis. We report the case of an 11‐year‐old boy with a 7‐year history of slowly progressive CD8+CD56+ mycosis fungoides of the cytotoxic immunophenotype. His trunk and extremities were affected by extensive pale‐erythematous patches and plaques with fine scaling. In addition, several poikilodermatous lesions were present on his thighs. Improvement was achieved by topical mometasone furoate treatment. On the basis of our observation, a brief review on cutaneous T‐cell lymphomas in childhood and on CD8+ subtypes in particular is given. Clinicopathological correlation is crucial for establishing the correct diagnosis and for estimation of the prognosis.     

Lymphoma or pseudolymphoma: A report of six cases and review of the literature

To explore and compare the clinical presentations and pathologic features of cutaneous pseudolymphomas (CPL) with primary cutaneous lymphomas. Review literature in order to improve the treatment of CPL. Six cases of CPLs were collected. The clinical, pathologic, and immunohistochemical features were performed and analyzed in Peking Union Medical College Hospital in 2018. Of six patients, the distributions and clinical manifestations of skin lesions are varied. The pathologic features consisted of atypical prominent lymphocytes infiltration. Of them, two cases imitated mycosis fungoides, one case mimicked primary cutaneous aggressive pidermotropic CD8+ cytotoxic T‐cell lymphoma, one case was diagnosed as Jessner‐Kanof lymphocyte infiltration and two cases primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorder. With respect to etiology, one was result from insects bite and the others were on account of drugs. All cases were treated with systemic or local glucocorticoid. The skin lesions and systemic symptoms showed notable improvement after treatment. Follow‐up visits were 2 years, half a year, and months, respectively, without relapse. These unique types of CPL were similar to cutaneous lymphomas in clinical manifestation and pathology. They were all sensitive to the treatment of externally or orally using glucocorticoid. The prognosis is generally good but needs long‐term follow‐up.     

Pagetoid reticulosis tumor cells with double expression of TCRγδ and TCRαβ: 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 TCRαβ and TCRγδ with an activated cytotoxic phenotype. It is worldwide accepted the mutual exclusive expression of TCRαβ and TCRγδ but six different studies, dealing with TCRγδ expression in various types of extra‐nodal lymphomas, reported cases whom tumor cells expressed simultaneously TCRαβ 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 TCRαβ with an immunoprofile consistent with an origin from TCRγδ+ T lymphocytes. This unusual subset has preferential, but not exclusive, skin localization and variable epidermotropism.     

Linfomas cutáneos. Parte II: otros linfomas cutáneos

Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30⁺ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish–violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.     

Indolent CD8+ lymphoid proliferation of acral sites: a clinicopathologic study of six patients with some atypical features

The authors report six further cases of a cutaneous lymphoid proliferation that share many of the features of a case series previously described as indolent CD8‐positive lymphoid proliferation of the ear. Previous reports of this entity have described the slow growth of cutaneous papules and nodules, with a predilection for the ear, associated with specific histopathologic and immunophenotypic features and a benign clinical course. These include the presence of a clear Grenz zone without epidermotropism, and a CD8⁺ granzyme B‐ immunophenotype with a low proliferative index. The current case series presents some atypical clinical features, including site of disease beyond the ear and recurrent disease. Despite this, indolent clinical evolution is apparent. Histopathologically, three of the six cases showed a moderate‐high proliferative index, while two cases had very focal epidermotropism and Pautrier collections. A single example had significant granzyme B expression. These previously unreported features add to our understanding of this rare entity, which is not currently recognized in the World Health Organization (WHO)/European Organization for Research and Treatment of Cancer (EORTC) classification.     

Indolent CD8-positive T-cell lymphoid proliferation of the ear: a report of two cases

The current classification of primary cutaneous T-cell lymphoma (CTCL) of the World Health Organization (WHO) includes primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma as a provisional entity awaiting cumulative data. Recent reports identify CD3/CD8-positive clonal T-cell lymphoid proliferations arising in the ear and nose that behave indolently and therefore defy currently established subclassification. Here, we report two cases of clonal CD8-positive/granzyme-B-negative T-cell lymphoid proliferations that arose in the ear and behaved indolently. Collectively, these cases suggest that an additional category of cutaneous indolent CD8-positive T-cell lymphoma may be necessary among the existing classification schemes.     

Primary CD56 + nasal-type T/natural killer-cell subcutaneous panniculitic lymphoma: presentation as haemophagocytic syndrome

Natural killer (NK) cells are large granular lymphocytes that mediate cytotoxic reactions which are not restricted by the major histocompatibility complex. In recent years it has become apparent that a minor proportion of malignant lymphomas expresses an NK-cell phenotype defined by its reactivity with the CD56 antibody. Primary purely cutaneous CD56 + lymphomas have rarely been reported. They share a generally aggressive course and are highly associated with Epstein-Barr virus. We describe a patient with a primary cutaneous nasal-type T/NK-cell lymphoma that presented as a haemophagocytic syndrome and showed an aggressive clinical course.     

Cutaneous CD30‐positive lymphoproliferative disorders with CD8 expression: a clinicopathologic study of 21 cases

Lymphomatoid papulosis (LyP) and cutaneous anaplastic large cell lymphoma (ALCL) belong to the spectrum of cutaneous CD30+ lymphoproliferative disorders, an indolent form of T‐cell lymphoproliferative disease. We reviewed 21 cases of CD30+ lymphoproliferative lesions expressing cytotoxic profile (CD8+). Seven cases of cutaneous ALCL, 2 cases of systemic ALCL involving the skin, and 12 cases of LyP. The cases of LyP were predominated by small lymphocytes exhibiting a prominent epidermotropic pattern consistent with either type B or type D LyP. Four cases showed co‐expression of CD56. The ALCL cases included myxoid features, pseudoepitheliomatous change, and an intravascular component. In all cases that were primary in the skin an indolent clinical course was seen while one patient with systemic myxoid ALCL is in remission following systemic multiagent chemotherapy. The paucity of other neutrophils and eosinophils and concomitant granulomatous inflammation were distinctive features in cases of type B and type D LyP. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful differentiating features from an aggressive cytotoxic CD8+ T cell lymphoma. In all cases that were primary in the skin an indolent clinical course was observed. CD30 and CD45 Ro positivity and a clinical course typical of LyP were useful in preventing a misdiagnosis of an aggressive cytotoxic CD8+ T cell lymphoma.     

Primary cutaneous CD8+ cytotoxic T‐cell lymphoma involving the epidermis and subcutis in a young child

CD8+ cytotoxic T‐cell lymphoma involving the skin represents a heterogeneous group of diseases that include subcutaneous panniculitis‐like T‐cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma, and ‘type D’ lymphomatoid papulosis. In this report, we describe a case of CD8+ cytotoxic T‐cell lymphoma involving both the epidermis and subcutis. The patient was a 6‐year‐old girl who presented with a 3‐year history of multiple plaques on her trunk and legs. The lesions had relapsed twice but responded well to prednisone. Histopathologic examination showed the proliferation of atypical lymphocytes in the epidermis, dermis and subcutaneous tissue. On immunohistochemical analysis, the atypical lymphocytes were positive for βF1, CD3, CD8, perforin, granzyme B and TIA‐1, but negative for T‐cell receptor (TCR) γ, CD4, CD30 and CD56. It was difficult to classify this tumor in terms of the known types of cutaneous lymphoma, and this case should be differentiated with subcutaneous panniculitis‐like T‐cell lymphoma and primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma.     

Cutaneous atypical papular CD8+ lymphoproliferative disorder at acral sites in a renal transplant patient

A 20‐year‐old woman presented with a 2‐month history of an acute symmetrical eruption, manifesting as asymptomatic ill‐defined erythematous macules and hyperkeratotic papules on the palms. The patient was a renal transplant recipient, and the lesions had developed 2 months post‐transplantation. Histologically, the eruption shared features of a reactive inflammatory condition called papular eruption of atypical CD8+ lymphocytes as well as primary cutaneous acral CD8+ T‐cell lymphoma (a provisional indolent entity in the new World Health Organisation classification of lymphoid neoplasms, 2016). The latter disorder has been described to occur at acral sites in immunocompetent patients, whereas the former has previously been described only in patients infected with human immunodeficiency virus. The lesions in our patient healed after topical treatment with corticosteroids and alteration of immunosuppressive therapy, supporting the role of immunosuppression in this case. We classified our patient's condition as lying in the spectrum of the aforementioned two conditions, but the relationship between both diseases remains to be clarified. Awareness of these unusual conditions may prevent the use of unnecessary aggressive therapies in similar patients.     

Immunophenotypic shift of CD4 and CD8 antigen expression in primary cutaneous T‐cell lymphomas: a clinicopathologic study of three cases

Primary cutaneous T‐cell lymphomas (CTCL) comprise a heterogeneous group of neoplasms with diverse clinical behavior. Mycosis fungoides (MF) is the most common type of CTCL. Immunophenotypical shift during progression of the disease is a rare event and its significance is unknown. We present three primary CTCL cases that showed an immunophenotypical shift and poor prognosis. Conventional hematoxylin/eosin and immunohistochemical‐stained sections were examined in all the cases. Molecular analysis for rearrangement of the T‐cell receptor (TCR) gene was performed in two cases. One case was classified as MF, while the other two lacked epidermotropism, and were considered primary cutaneous peripheral T‐cell lymphoma (PTCL), NOS. Two cases were CD3+/CD4+ and one case was CD3+/CD8+ at diagnosis. The first two patients suffered many relapses and eventually, new CTCL lesions with a CD3+/CD8+ phenotype were observed. Both cases revealed identical clonal TCR rearrangements on the initial and late lesions, supporting the interpretation of a single clonal proliferation with different phenotypes. The third case progressed with skin recurrences and pulmonary lesions with a predominant CD3+/CD4+/CD8? phenotype. All cases manifested poor prognosis and two patients died of lymphoma. Immunophenotypical shift between CD4 and CD8 in CTCL seems to be a rare phenomenon that may be associated with disease progression.     

Primary cutaneous γδ-T-cell lymphoma treated with low-dose methotrexate and narrowband ultraviolet B irradiation: report of a case with testicular involvement

Primary cutaneous γδ-T-cell lymphoma (CGD-TCL) is a rare entity of cutaneous T-cell lymphomas (CTCL) and is characterized by tumoral growth of mature γδ-T-cell expressing cytotoxic molecules. The prognosis of CGD-TCL is generally worse than other CTCL. However, relatively indolent patch/plaque lesions have been described suggesting the heterogeneous nature of this entity. Here, we present a case of CGD-TCL with various skin manifestations, such as erythematous plaques/tumors and subcutaneous panniculitis-like lesions. During the follow up, testicular involvement was detected, which was surgically removed. Histopathology showed mixed features from epidermotropism, dermal infiltration and subcutaneous panniculitis-like lesions depending on the clinical manifestations. The tumor cells were positive for CD3 and revealed cytotoxic markers, TIA-1 and perforin, but not for CD4, CD8, CD20, CD56, TCRβF1 or EBER. Topical glucocorticoid ointment, narrowband ultraviolet B (NB-UVB) irradiation and low-dose methotrexate (MTX) were effective to control these skin lesions. No visceral involvement was detected thereafter. While CGD-TCL is usually associated with poor prognosis, it seems to be composed of various clinical manifestations, and NB-UVB and low-dose MTX could be a choice for indolent patch/plaque and possibly nodular lesions, especially for the aged.