Richter transformation (RT) refers to the progression of chronic lymphocytic leukemia, the most prevalent leukemia among adults, into a highly aggressive lymphoproliferative disorder, primarily a diffuse large B-cell lymphoma. This is a severe complication that continues to be a therapeutic challenge and remains an unmet medical need. Over the last five years, significant advances have occurred in uncovering the biological processes leading to the RT, refining criteria for properly diagnose RT from other entities, and exploring new therapeutic options beyond the ineffective chemotherapy. This review summarizes current knowledge in RT, including recent advances in the understanding of the pathogenesis of RT, in the classification of RT, and in the development of novel therapeutic strategies for this grave complication.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare cutaneous T cell malignancy of cytotoxic T cell origin. It is frequently associated with autoimmune diseases. It is known to preferentially involve subcutaneous adipose tissue and histologically resembles lupus panniculitis. The aetiology and risk factors of SPTCL are unclear and there are limited studies available since this entity was initially described in 2001. There are even fewer case reports describing the association between SPTCL and chronic lymphocytic leukemia (CLL). In this article, we present a case of SPTCL arising during treatment for CLL. We conducted an extensive review of literature to delve into the possible risk factors for SPTCL development in association with CLL, including pre-existing haematological malignancies, autoimmune conditions, immunomodulation and immunosuppressive chemotherapy.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular helper immunophenotype and similar mutations consisting of TET2 or DNMT3A alterations, IDH2 R172K/M, and RHOA G17V. The 3 patients received chemotherapy. One died of early AITL relapse. The other 2 remained in complete remission of AITL, 1 died with recurrent CLL, and 1 of acute myeloid leukemia. These observations expand the spectrum of T-cell lymphoma entities that occur in association with CLL/SLL, adding AITL to the rare variants of aggressive neoplasms manifesting as Richter syndrome. Given that disturbances of T-cell homeostasis in CLL/SLL affect not only cytotoxic but also helper T-cell subsets, these may contribute to the emergence of neoplasms of T follicular helper derivation.

Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood.

To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma.

Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing.

We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour.

These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is associated with an increased risk of a second malignancy.

We conducted a retrospective clinicopathologic review of 12 patients with CLL/SLL who developed a second lymphoma in the skin. Demographic data, clinical information, and histopathology from 31 biopsies were recorded. Cases of secondary cutaneous involvement by CLL/SLL (leukemia cutis) and non-primary cutaneous lymphomas were excluded.

A wide variety of primary cutaneous lymphomas was identified, including classic mycosis fungoides (3), cutaneous marginal zone lymphoma (2), primary cutaneous peripheral T-cell lymphoma unspecified (2), folliculotropic mycosis fungoides (1), Sézary syndrome (1), cutaneous gamma-delta T-cell lymphoma (1), cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (1), and cutaneous anaplastic large cell lymphoma (1). A male predominance was observed, and the average age was 74.1 years. In all patients, CLL/SLL predated the development of the second lymphoma, which was aggressive in the majority of cases (58%). Aggressive cytotoxic T-cell lymphomas, generally rare neoplasms, were relatively common (30%).

CLL/SLL patients may develop a second lymphoma in the skin, which may be aggressive. Atypical cutaneous lymphoid infiltrates in this patient population should not be assumed to represent secondary CLL/SLL involvement and require thorough immunohistochemical analysis.

Innate limitations of morphological diagnosis of T/NK-cell neoplasms mean that they can be misdiagnosed or missed, especially when mixed with a variety of benign and reactive conditions. The aim of this study was to investigate the application value of multiparameter flow cytometry immunophenotyping (MFCI) in screening and diagnosing T/NK-cell neoplasms with cytology specimens.

The clinical and pathological characteristics of 1028 newly diagnosed cases from Fudan University Shanghai Cancer Center who provided a cytology specimen between June 2010 and January 2016 with correlated histology diagnosis and clinical confirmation were retrospectively reviewed. MFCI was used for screening, diagnosis and typing. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in diagnosis of T/NK-cell neoplasms were calculated.

There were 606 males and 422 females in 1028cases, with a mean age of 47.5 years (range 9-86 years). Specimens used for cytologic diagnosis included 996 FNAs, 2 US-FNAs, 13 EUS-FNAs and 17 effusions. Screening for types of lymphoma of MFCI, 139 (13.52 %) cases were T/NK cell lymphoma, 3 (0.29 %) cases were B cell lymphoma T-NHL and B-NHL coexist. A total of 146 suspected T/NK-cell neoplasms were screened out (sensitivity = 94.64 %, specificity = 95.63 % PPV = 72.60 %, NPV = 99.32 %) by MFCI, with 112 (76.71 %) histologically confirmed cases and 6 (4.11 %) false-negative cases identified (3 cases diagnosed as B-cell neoplasms and 1 case as T-cell neoplasm with B-cell neoplasm, which also were confirmed by gene rearrangement. 2 cases were suspicious T-cell-immunophenotypic abnormalities). When used at the diagnostic level, a total of 88 T/NK-cell neoplasms were identified (sensitivity = 68.75 %, specificity = 98.80 %, PPV = 87.50 %, NPV = 96.28 %) with 11 false-positive cases recognized, 9 of which showed typical immunophenotypic T-cell neoplasms features, and 2 exhibited aberrant T immunophenotype.

MFCI has high sensitivity and specificity in the screening and diagnosis of T/NK-cell neoplasms and may be useful as an alternative diagnosis method in cytology specimens.

Second hematologic cancers in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) are well documented and include Hodgkin lymphoma, therapy-related acute myeloid leukemia/myelodysplastic syndromes, and transformation to diffuse large B-cell lymphoma. Although cutaneous T-cell lymphoma (CTCL) has been reported in patients with CLL, the incidence and comparison to expected rates are unknown. We evaluated the incidence of CTCL among patients with CLL or other non-Hodgkin lymphoma (NHL) subtypes using data from the Surveillance, Epidemiology, and End Results (SEER) Program.

We searched the SEER 13 registries for patients with a diagnosis of CLL and NHL between 1992 and 2008. Among patients identified, we evaluated the incidence of CTCL.

Among 31,286 patients with CLL, the incidence of CTCL was not significantly higher in men than women: 104.2 (95% CI, 50.0-191.8) and 28.1 (95% CI, 3.4-101.3) per 1,000,000 person-years, respectively (P = 0.06). Among 97,691 patients with NHL, the incidence of CTCL was similar in men and women (97.9 [95% CI, 62.0-146.9] and 92.0 [95% CI, 56.2-142.1] per 1,000,000 person-years, respectively; P = 0.84). The incidence of CTCL among males with CLL (standardized incidence ratio [SIR], 3.0 [95% CI, 1.4-5.5]), males with NHL (SIR, 3.7 [95% CI, 2.3-5.5]), and females with NHL (SIR, 5.9 [95% CI, 3.6-9.1]) was significantly higher than expected in the general population (all P < 0.001).

The risk of CTCL is greater in men with CLL than in the general population. In patients with NHL, both men and women are at greater risk for CTCL than in the general population.

The development of both a T- and B-cell lymphoproliferative disorder in one patient is an unlikely coincidence due to the low prevalence of each malignancy. We report a 65-year-old man with a previously documented history of B hairy cell leukemia, who presented with a new-onset acneiform eruption of his scalp, face, trunk, back, and extremities. Routine pathology of the skin lesions with immunohistochemical stains and molecular studies were consistent with a folliculotropic mycosis fungoides. B hairy cell leukemia and mycosis fungoides occurring in the same patient seems to be a rare phenomenon with only 5 cases reported in the literature.

A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.

Mycosis fungoides (MF), the most common primitive cutaneous T-cell lymphoma, can undergo transformation in about 10% of cases. Transformed mycosis fungoides (T-MF) is often associated with the appearance of a CD20 component. The aim of this study was to analyze whether such cells are reactive or lymphomatous and to evaluate their prognostic impact. Among 311 T-MFs from the French Cutaneous Lymphoma Study Group registry, we studied 148 cases. CD20 was expressed in 88 cases (59%). The proportion of CD20 cells among T-MF lesions was <10% for 54 cases (38%), 10% to 49% for 71 cases (81%), and >50% for 17 cases (19%). We focused the study on 23 cases that contained >50% CD20 cells. To evaluate the nature of the CD20 component, we used immunohistochemistry (2 anti-CD20 antibodies, L26 and 7D1 clones, and 2 other anti-B-cell antigen antibodies, CD22 and PAX5) and a double-stain immunofluorescence technique (anti-CD20 and anti-CD3 antibodies). The clonality of B cells was studied by polymerase chain reaction. Three profiles were observed. In 15 of the 23 cases, the CD20 cells were reactive. In 6 cases, CD20 protein was aberrantly expressed in T-MF lesions. Lastly, there were 2 composite lymphomas (T-MF infiltrate with a B-cell follicular lymphoma). In view of this series, we propose a simple algorithm to help pathologists evaluate the nature of the CD20 component associated with T-MF. Although statistically not significant, there was a trend toward a worse prognosis in the presence of >50% CD20 cells and of a nodular perifollicular pattern of this component.

We examined the course of cutaneous T-cell lymphoma (CTCL), which has been associated with chronic lymphocytic leukemia (CLL) in patients with CLL.

A search was conducted of the master diagnosis index at our institution to identify patients with both CLL and CTCL from 1980 to 2010. A retrospective chart review was then conducted.

Of the 14 patients with CTCL and CLL, eight had mycosis fungoides (MF; two with patch stage, two with plaque stage, two with tumor stage, and two with erythrodermic stage), four had Sézary syndrome, one had natural killer cell lymphoma involving the skin, and one had peripheral T-cell lymphoma involving the skin. Eight had concurrent diagnoses, five received a CLL diagnosis first, and one received a CTCL diagnosis first. Ten patients were deceased at the time of data abstraction due to unknown causes (n = 4), lymphoma (n = 2), pneumonia (n = 2), MF (n = 1), or respiratory failure (n = 1). Of the nine patients with concurrent or prior CTCL, seven were deceased, with a median time to death of 10.2 months (range, 6-89 months). Of the five patients with CLL prior to CTCL, three were deceased at 18, 27, and 47 months, respectively, after the CTCL diagnosis. The median survival for the two groups was 12 and 47 months, respectively.

Patients with CTCL concurrent with or prior to CLL have a worse overall survival than patients with CLL in whom CTCL later develops. Larger studies are needed.

Composite lymphoma of T-cell and B-cell type is uncommon, and the one occurring primarily on skin is extremely rare. Herein, we report a unique case of composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient. The patient presented with multiple erythematous patches, plaques, and nodules on the upper arms, scalp, and trunk. Four punch biopsies of arm and scalp lesions demonstrated lymphoid infiltrate in superficial to deep dermis with a characteristic zone distribution of T-cell and B-cell components. T cells were distributed in papillary and perifollicular dermis and displayed a larger size with convoluted nuclei, whereas B cells were small sized, assuming nodular infiltrate in mid-deep dermis with coexpression of CD5. Molecular test detected clonal rearrangement of both TCRG and IGH/K genes with identical amplicons for each gene in all 4 biopsies. Clinical staging revealed no extracutaneous lesions. A multidisplinary approach is emphasized to establish a definitive diagnosis.

The relationship between compromised immune system and the development of malignancy, generalized dermatitis, and infection after sulfur mustard gas exposure has been established.

We introduce a 58-year-old man with an abrupt, de novo and erythrodermic eruption in 2002 that was previously exposed to sulfur mustard during the Iran - Iraq war in 1987. Six weeks after the onset of diffuse eruption, he developed papules on the glans penis and generalized dermatophytosis. A biopsy of his eruption was consistent with cutaneous T-cell lymphoma/Sézary syndrome. A complete blood count demonstrated leukocytosis, eosinophilia and atypical lymphocytosis. Subsequently, Sézary syndrome was confirmed and T-cell count with increased CD4/CD8 in flow cytometry. The biopsy of his penile papules was consistent with Kaposi's sarcoma.

These findings suggest a causative relationship between sulfur mustard gas exposure, cutaneous T cell lymphoma and immune compromised state with opportunistic infections.

Composite lymphomas (CLs) consisting of 2 indolent B-cell lymphomas are rare. We present 2 CL cases composed of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), each with unique clinicopathologic features. In the first case, the FL was negative for IGH-BCL2 and harbored a novel IGH-associated translocation; in the second case, the CL manifested in the skin. The individual components in both CLs were derived from different B-cell clones. This is the first complete characterization, including molecular analysis, of CLs composed of leukemic CLL and FL and the first report of a cutaneous CL derived from 2 low-grade B cell lymphomas. Our results provide additional supporting evidence that CLs of indolent B-cell lymphomas are biclonal and suggest that they are pathogenetically different from CLs composed of a low-grade B-cell lymphoma and an aggressive B-cell lymphoma or Hodgkin lymphoma, which are usually clonally related.

The spectrum of skin diseases that occurs in the oncology patient differs somewhat from that seen in other immunosuppressed populations. We review the cutaneous manifestations of invasive mold infections in the leukemia/lymphoma population. Aspergillus mold infections are now the leading infectious cause of death in this population. We also review the pustular eruption caused by a new class of chemotherapy for solid malignancies. An update on cutaneous graft-versus-host disease appears elsewhere in this journal. Cutaneous squamous cell carcinomas and basal cell carcinomas occur more frequently in the chronic lymphocytic leukemia and non-Hodgkin's lymphoma population; this is discussed, as is the more aggressive clinical course of these tumors.

In patients suffering from primary cutaneous lymphomas, secondary malignancies of various origin may develop. However, the frequency of a second neoplasm deriving from another lymphoid lineage is still unclear and may be underestimated. We screened all our patients with primary cutaneous lymphomas from a 4-year recruitment period for a coexisting secondary lymphoproliferative disorder. The cohort comprised of a total of 82 patients with primary cutaneous lymphomas, 62 with primary cutaneous T-cell lymphoma (CTCL), 18 with primary cutaneous B-cell lymphomas, and two with CD4+/CD56+ hematodermic neoplasm/blastic lymphomas. Seven patients (8.5%) were identified with a coexisting lymphoma of a different lymphoid lineage. Four patients with Sézary syndrome (SS) suffered from systemic B-cell lymphoma. Two of these developed SS after chemotherapy of their B-cell lymphoma. The other three patients with various types of skin lymphomas (SS, Mycosis fungoides [MF], primary cutaneous marginal zone lymphoma) developed Hodgkin's disease (hairy cell leukemia). Our data indicate that patients with primary cutaneous lymphomas have an elevated risk for the development of a secondary lymphoproliferative disorder even without previous chemotherapy. Possible explanations for this association include a genetic predisposition, alterations in early progenitor cells, underlying viral infections, and/or stimulation of a B-cell clone by the malignant helper T cells of the primary CTCL and vice versa.

The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse.

To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms.

Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period.

Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled.

This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

We report a case of an intestinal peripheral T-cell lymphoma (PTCL) with a concurrent diffuse large B-cell lymphoma (DLBL) involving the ileum and a regional lymph node. The patient presented with an abdominal mass. The terminal ileum showed a diffuse and monotonous population of small CD3-positive T cells. The T-cell receptor gamma (TCRgamma) gene was rearranged by PCR while the immunoglobulin heavy chain (IgH) gene was not. A separate section of the ileum showed a colliding large B-cell proliferation. The regional lymph node showed a diffuse proliferation of large centroblasts positive for CD20 and CD79a admixed with small T cells and showed a rearranged IgH receptor gene without evidence of a clonally rearranged TCRgamma gene. Both the PTCL and DLBL components were negative for EBV. A review and analysis of the pertinent literature describing composite T- and B-cell lymphomas is performed and reported.

The simultaneous appearance of mycosis fungoides (MF) and B-cell chronic lymphocytic leukemia (B-CLL) in the same patient is extremely rare. Only seven cases have been described in literature. A 72-year-old patient was diagnosed with coincident MF, stage Ib, and B-CLL, Binet stage A. Hypotheses on simultaneous occurrence of B- and T-cell malignancies as well as a new therapeutic option are discussed.

The presence of a dominant B- or T-cell clone is an important diagnostic criterion for distinguishing cutaneous lymphomas from lymphoid reactive infiltrates. Rarely, a combined B- and T-cell rearrangement can be detected from a single sample. In such instances, genotypic analysis does not permit differentiation of the coexistence of a T- and B-cell lymphoma from a single clone harbouring a monoclonal rearrangement for both immunoglobulin heavy chain and T-cell receptor genes. We herein report a case of a skin tumour consistent with a dense cutaneous lymphoid infiltrate showing a double prominent B- and T-cell component. A dual B- and T-cell clonality was detected by polymerase chain reaction from whole-tissue DNA sample. Genotypic analysis with DNA, obtained after laser-assisted microdissection from the B-cell population, again showed both T- and B-cell monoclonal rearrangements. Conversely, the microdissected T-cell population did not reveal a clonal pattern. The diagnosis of cutaneous B-cell lymphoma with a dual B- and T-cell genotype was established. This description illustrates the diagnostic usefulness of laser-capture microdissection in cutaneous lymphomas presenting dual genotype.

The simultaneous presentation of chronic lymphocytic leukaemia (CLL) and cutaneous T-cell lymphoma (CTCL) is a very rare occurrence where optimal treatment is unknown. We present the case of a 65-yr-old man who was successfully treated with alemtuzumab monotherapy for both disorders, but at a cost of severe infectious morbidity and prolonged pancytopenia.

A case of composite lymphoma (CL) arisen in the parotid gland in a 58-year-old male is reported. Histologically, most of the tumor region was follicular lymphoma (FL), grade 2. However complicating classical Hodgkin lymphoma (CHL) was noted inside the lesion. There have been a few reports of composite lymphoma, complicated by multiple histologic types in the same organ. Extra-nodal cases are particularly rare. This is a very significant case with regard to differences between B cell-derived non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) and its histological origin.

Chronic lymphocytic leukaemia (CLL) is a malignancy characterized by clonal expansion of B lymphocytes with distinct morphology and immunophenotype. The dermatological literature relating to CLL is sparse. A global descriptive survey of a large number of CLL patients has not previously been published.

To report the spectrum of dermatological conditions seen in a large series of CLL patients.

Skin complications in patients with established CLL were identified retrospectively from clinical and photographic records, principally a database of over 750 consecutive cases. These events were classified, enumerated and compared.

Forty patients with 125 skin manifestations were identified and studied. Forty-one manifestations had documented clinical or histological atypia. In 21 of these 41 complications there had been no prior immunosuppressive therapy. We observed that cutaneous malignancies frequently presented atypically both clinically and histologically. There were 18 patients with 56 instances of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), and clinical atypia was more common with SCC than with BCC. Other cutaneous findings included varicella zoster (n = 6), leukaemia cutis (n = 3), acute graft-versus-host disease (n = 5), cutaneous drug eruptions (n = 9), multiple warts (n = 3), herpes simplex (n = 3), cutaneous T-cell lymphoma (n = 2), eosinophilic folliculitis (n = 2), malignant melanoma (n = 2) and Merkel cell tumour (n = 2).

We have identified a range of dermatological conditions in CLL patients, with a tendency to atypical presentations. The atypia was independent of prior chemotherapy.

Chronic lymphocytic leukemia (CLL) is associated with increased risk of malignancy, but the occurrence of other lymphomas, in particular T-cell lymphomas, is rare. We identified 7 cases of peripheral T-cell malignancy associated with B-cell-derived CLL from the files of two institutions over a 20-year period. The presence of both B and T lymphoproliferative disorders was confirmed in all cases by immunophenotype and in 6 cases by gene rearrangements. Six patients developed peripheral T-cell lymphoma (PTCL), unspecified, during the course of CLL (10-168 months). In all 5 evaluable cases, the cells had a cytotoxic T-cell phenotype; the sixth case was CD56+, but TIA-1 and Granzyme B could not be studied. A seventh patient with CLL developed mycosis fungoides, and an aggressive NK cell leukemia. To investigate possible risk factors for the development of PTCL, we screened 100 unselected peripheral blood samples from newly diagnosed CLL patients by PCR for the presence of clonal T cell populations. We found evidence of clonal T-cell expansion in 8 patients and increased lymphocytes with large granular lymphocyte morphology in 7 of 8 cases. The immunophenotype was assessed by multicolor flow cytometry and in 4 cases the T-cell expansion was composed of either CD3+/CD8+ or CD3+/CD4-/CD8- cells. The cytotoxic nature of the clonal T-cell expansions in the peripheral blood correlates with the cytotoxic nature of the PTCLs, but their role in the subsequent development of T-cell lymphomas is still unclear. PTCL following CLL should be distinguished from typical Richter syndrome, which it can mimic clinically.

A composite lymphoma is defined as the simultaneous occurrence of two histologically different types of lymphomas situated in one anatomical location. Reports of composite B- and T-cell lymphomas, especially in the head and neck region, are rare. We describe a 76-year-old Taiwanese aboriginal female patient clinically presenting with a midfacial necrotizing lesion (MNL). Microscopic examination of the incisional biopsy specimen revealed extensive surface necrosis with infiltrates of inflammatory cells. Beneath the necrotic surface, there appeared to be two distinct populations of pleomorphic lymphoid cells exhibiting the characteristic features of the angiocentric distribution of the tumor cells and evidence of angiodestruction. Immunohistochemical staining revealed that these atypical lymphoid cells were positive for LCA, CD45, CD5, CD20, CD3 epsilon, CD8, bcl-2 and bcl-6 and negative for CD56, CD4, CD68, keratin, S-100, kappa and lambda. Furthermore, these atypical lymphoid cells also expressed EBV-encoded nuclear RNAs (EBERs) following in situ hybridization. Therefore, this was a case of composite lymphoma: angiocentric T-cell lymphoma (ATCL) (CD8+ cytotoxic/suppressor T-cell) and diffuse large B-cell lymphoma (DLBL) associated with the Epstein-Barr virus (EBV) and presenting clinically as MNL.

Chronic lymphocytic leukemia (CLL) is a generalized malignancy of the lymphoid tissue characterized by an accumulation of monoclonal lymphocytes, usually of the B cell type. Involvement of the central nervous system is a rare complication, usually seen in T cell leukemias. We report a case of a 78-year-old woman with B cell CLL and meningeal infiltration by both B and T lymphocytes, although predominantly T lymphocytes. Neurological symptoms were the first manifestation of this disease. Computed tomography of the brain was negative. The diagnosis of leukemic meningitis was made on the basis of the examination of the cerebrospinal fluid, and which included cytological and flow cytometry analysis. The patient was given systemic chemotherapy in the form of chlorambucil and intrathecal administration of methotrexate and dexamethasone. After recovery, she had regular follow-up. We assume that this rare case of CLL might have been biclonal, with both B and T cell types.

We report a rare case of composite angioimmunoblastic T-cell lymphoma (AILT) and diffuse large B-cell lymphoma occurring in a 48-year-old woman with generalized lymphadenopathy and hepatosplenomegaly. The patient initially sought care at a local hospital with a single enlarged left cervical lymph node. Histologic examination of the node was interpreted as an atypical immunoblastic proliferation. She developed generalized lymphadenopathy 10 months later and was referred to our institution for further evaluation. The recent biopsy of the cervical node showed typical features of AILT Flow cytometric immunophenotyping identified an aberrant CD4+ T-cell population that lacked surface CD3. Polymerase chain reaction analysis of the T-cell receptor gamma gene revealed a clonal rearrangement. In addition to the AILT, the lymph node showed partial involvement by a diffuse large B-cell lymphoma. The B lymphoma cells and admixed immnunoblasts and Reed-Sternberg-like B cells in the AILT were positive for Epstein-Barr virus (EBV) by in situ hybridization. Ourfindings raise the possibility that the EBV-associated large B-cell lymphoma is a secondary event in AILT via EBV infection or reactivation followed by clonal expansion of an immortalized EBV-infected B cell clone.