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Background
Peripheral T-cell lymphomas (PTCL) is a group of non-Hodgkin's lymphomas sharing a derivation from neoplastic T cells. The clinical and histologic presentations of each of these lymphomas is diverse. The following is the Revised European American Lymphoma Classification (REAL Classification) and Proposed World Health Organization Classification for Mature T- and Natural Killer-cell Neoplasms.
T-cell prolymphocytic leukemia
T-cell granular lymphocytic leukemia
Aggressive Natural Killer cell leukemia
Adult T-cell leukemia/lymphoma (HTLV-1+)
Extranodal Natural Killer/T-cell lymphoma, nasal type
Enteropathy-type T-cell Lymphoma
Hepatosplenic gamma-delta T-cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Mycosis fungoides/Sezary syndrome
Anaplastic Large cell lymphoma, T/null cell, primary cutaneous type
Peripheral T-cell lymphoma, unspecified
Angioimmunoblastic T-cell lymphoma, (AILD)
Anaplastic large cell lymphoma CD30-positive, T/null cell, primary systemic typePTCL have varied presentations but most present with generalized and retroperitoneal lymphadenopathy. The mediastinum is usually spared although may occur in younger patients. Skin lesions may occur varying from plaques and papulosquamous changes to nodules. B symptoms including fever, weight loss, and night sweats are present in about 50% of patients and usually with advanced disease.
OUTLINE
CHARACTERIZATION Radiographs CT scan and MRI Laboratory Markers Detection of Clonal T-Cell Receptor-gamma Gene Rearrangement by PCR/Temporal Temperature Gradient Gel Electrophoresis
Dan Zhu, MD, PhD,1 Marshall E. Kadin, MD,2 and Michael Samoszuk, MD1
Am J Clin Pathol 2001;116:527-534 Abstract quote
Limited combinatorial and junctional diversity in TCR-gamma gene rearrangement can result in amplification products that are difficult to interpret when analyzed by conventional gel electrophoresis methods that separate DNA based on size (polymerase chain reaction [PCR]/polyacrylamide gel electrophoresis [PAGE]). We describe a simple approach to the detection of clonal TCR-gamma gene rearrangement using temporal temperature gradient gel electrophoresis (TTGE) that uses a gradual and uniform increase in the temperature of a constant denaturing gel to resolve different DNA molecules based on base pair composition.
We tested 42 clinical specimens (30 blood specimens and 12 formalin-fixed paraffin-embedded tissues) for T-cell clonality by PCR/PAGE and PCR/TTGE. Concordant results were obtained in only 22 specimens (52%). Of the 20 discordant cases, 18 samples were positive by TTGE and negative by PAGE. For all of the discordant cases, the TTGE yielded results that correlated better with the clinical data than did the PAGE method.
We conclude that PCR/TTGE is more accurate and easier to perform than current methods for detecting clonal populations of T cells.
PERIPHERAL BLOOD Flow Cytometric Assessment of TCR-V b Expression in the Evaluation of Peripheral Blood Involvement by T-Cell Lymphoproliferative Disorders A Comparison With Conventional T-Cell Immunophenotyping and Molecular Genetic Techniques
William G. Morice, MD, PhD, Teresa Kimlinger, Jerry A. Katzmann, PhD, John A. Lust, MD, PhD, Paul J. Heimgartner, Kevin C. Halling, MD, PhD, and Curtis A. Hanson, MDAm J Clin Pathol 2004;121:373-383 Abstract quote
Molecular genetic T-cell receptor (TCR) and flow cytometric analysis using antibodies to conventional T-cell antigens and TCR b -chain variable region families (TCR-V b ) were performed in 65 peripheral blood specimens evaluated for potential involvement by a T-cell lymphoproliferative disorder (TCLPD). A normal or reactive conventional T-cell immunophenotype was present in 36 cases; TCR-V b flow cytometric and molecular TCR analyses were negative for clonality in 32 and 27 of these cases, respectively.
In the remaining normal and reactive cases, one or both methods seemed to detect dominant cell populations in settings with limited T-cell diversity.
We identified 29 TCLPDs; all studied cases had clonal molecular TCR results; 23 TCLPDs had clonal TCR-V b flow cytometric results; the remaining were suggestive of (n = 3) or negative (n = 3) for clonality. TCR-V b flow cytometric analysis is a powerful clinical laboratory tool that can be used to aid in the rapid diagnosis of peripheral blood involvement by T-cell malignant neoplasms.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION General Almost 2/3 of patients present with stage III or IV disease Adult T cell leukemia/lymphoma (HTLV-1) Caused by HTLV-1 infection
Usually present with stage IV disease with generalized lymphadenopathy, skin, liver, spleen, and bony lytic lesions
HypercalcemiaAngioimmunoblastic T-cell lymphoma (AIL) Generalized lymphadenopathy with hepatosplenomegaly, fever, and rash
May have associated dysproteinemia with polyclonal hypergammaglobulinemia
Hepatosplenic T-cell lymphoma Liver and spleen preferentially involved
Neoplastic cells positive for gamma/delta T cell receptorEnteropathy type T-cell lymphoma (Intestinal T-cell lymphoma, Ulcerative jejunitis, malignant histiocytosis of the intestine) Adults with a history of malabsorption and abdominal pain
May present with intestinal perforation
Jejunum most common location with multiple fociGastrointestinal T cell lymphoma: predominant cytotoxic phenotypes, including alpha/beta, gamma/delta T cell and natural killer cells.
Katoh A, Ohshima K, Kanda M, Haraoka S, Sugihara M, Suzumiya J, Kawasaki C, Shimazaki K, Ikeda S, Kikuchi M.
First Department of Pathology, School of Medicine, Fukuoka University, Japan.
Leuk Lymphoma 2000 Sep;39(1-2):97-111 Abstract quote
Gastrointestinal T cell lymphoma (TCL) is a rare subset of peripheral TCL, presenting with or without cytotoxic phenotype, a history of coeliac disease (CD) and enteropathy. However, CD is rare in Japan.
Here, we describe the clinicopathological features of 18 Japanese cases. Lesions were found in the small intestine (n=13), stomach (n=3) and colon (n=2). Seven patients presented with enteropathy but none had a history of CD. Lymphomas appeared as ulceration (n=11), tumour formation (n=6), or polypoid growth (n=1).
Histologically (REAL classification), neoplastic lesions were composed of intestinal type T cell lymphoma (ITCL, n=13, including one case with NK type), anaplastic large cell (ALCL, n=2), adult T cell leukaemia/lymphoma (ATLL, n=2), and lymphoblastic type (n=1). Epstein Barr virus infection was detected by EBER-1 in situ hybridization in 6 of 11 cases with ITCL but not in the other types. ALCL expressed CD30. CD56 was expressed in 3 of 11 cases of ITCL but not in other types. Among the 10 examined cases, 8 were alphabeta T cell type [CD2+, CD3+, T cell receptor (TCR)delta-1-, betaF1+], one was gammadelta T cell type [CD2+, CD3+, TCRdelta-1+, betaF1-], and the remaining case expressed natural killer (NK) cell type [CD2+, CD3-, CD56+, TCRdelta-1-, betaF1-]. Among the 8 examined cases, 3 expressed CD103 molecule, which was associated with extrathymic T cells of intraepithelial lymphocytes. All cases except ATLL expressed the cytotoxicity-associated molecule of TIA-1, and 11 of 14 TIA-1 positive cases expressed activated cytotoxic molecules of perforin, granzyme B, and/or Fas ligand.
Despite the morphological, genetic and phenotypic heterogeneity, prognosis was poor, and 11 of 13 patients with small intestinal lesions died albeit appropriate treatment, but 3 of 4 patients with gastric or colonic lesions were still alive. The main cause of death was intestinal perforation. The latter might be due to the site specificity of small intestine and tumour cytotoxicity.
Expression of killer cell inhibitory receptors is restricted to true NK cell lymphomas and a subset of intestinal enteropathy-type T cell lymphomas with a cytotoxic phenotype.
Dukers DF, Vermeer MH, Jaspars LH, Sander CA, Flaig MJ, Vos W, Willemze R, Meijer CJ.
Department of Pathology, Vrije Universiteit, Amsterdam, The Netherlands.
J Clin Pathol 2001 Mar;54(3):224-8 Abstract quote
BACKGROUND/AIMS: Killer inhibitory receptors (KIR) have a modulating effect on the cytotoxic functions of natural killer (NK) cells and T cells. Because lymphoma cells often have the same receptors as their non-neoplastic counterparts, this study investigated the expression of KIR on well defined groups of NK and T cell lymphomas, with and without a cytotoxic phenotype, from different sites of origin.
METHODS: Nine CD56+/CD3- NK cell lymphomas, 29 CD3+/CD56- T cell lymphomas with a cytotoxic phenotype, and 19 T cell lymphomas without a cytotoxic phenotype were stained for KIR using monoclonal antibodies specific for CD94, CD158a, and CD158b. In addition, the expression of KIR was studied on normal lymphoid tissues.
RESULTS: KIR expression was seen in five of nine true NK cell lymphomas including three of four nasal, one of four cutaneous, and one of one intestinal lymphoma nasal type. Double staining for CD56 and CD94 in normal lymphoid tissues revealed that KIR was predominantly expressed by CD56+ NK cells and sporadically on CD8+ T cells. Moreover, enteropathy-type T cell lymphomas with a cytotoxic phenotype showed KIR expression (three cases expressing CD94 and one case expressing CD158a). All nodal and extranodal nonintestinal T cell lymphomas with or without a cytotoxic phenotype lacked expression of KIR.
CONCLUSIONS: These results show that KIR expression is restricted to CD56+/CD3- true NK cell lymphomas originating from the nose, gut, and skin, as well as in a subset of extranodal T cell lymphomas originating from the small intestine, which possessed a cytotoxic phenotype. Thus, the presence of KIR on NK/T cell lymphomas seems to mimic the distribution of KIR found on NK and T cells in normal lymphoid tissue.
Anaplastic Large Cell lymphoma (CD30+) T-cell lymphoma with high content of epithelioid histiocytes (Lymphoepithelioid lymphoma, Lennert's lymphoma) Epithelioid histiocytes and polymorphic collection of inflammatory cells Am J Surg Pathol 2000;24:1627-1633
May be variant of a cytotoxic T-cell lymphoma
CD3+
TIA-1 was positive in 7/10 cases
Granzyme B 4/10 positiveOTHER ORGANS CENTRAL NERVOUS SYSTEM
Primary central nervous system cytotoxic/suppressor T-cell lymphoma: report of a unique case and review of the literature.Liu D, Schelper RL, Carter DA, Poiesz BJ, Shrimpton AE, Frankel BM, Hutchison RE.
Am J Surg Pathol 2003 May;27(5):682-8 Abstract quote Peripheral T-cell lymphoma primary to the central nervous system is a rare occurrence.
The authors report a case of an 89-year-old woman who presented with a 3-month history of worsening confusion and recent onset of headache, nausea and vomiting, and upper limb tremors. Computed tomography and magnetic resonance imaging examinations demonstrated a 4.5-cm solitary brain mass in the right basal ganglia with compression along the ventricular system. No other lesion was found in the patient.
Histologic and immunohistochemical studies of a stereotactic biopsy of the mass showed a T-cell lymphoproliferative lesion positive for CD3, CD8, CD57, and T-cell intracellular antigen 1 and negative for CD4, CD56, CD30, anaplastic lymphoma kinase, and CD20. A monoclonal T-cell receptor-gamma gene rearrangement was detected by polymerase chain reaction analysis of genomic DNA isolated from paraffin-embedded tumor tissue sections. These findings were consistent with peripheral T-cell lymphoma of cytotoxic/suppressor phenotype, resembling the phenotype of T-cell large granular cell leukemia.To the authors' best knowledge, this represents the first reported case of primary brain T-cell lymphoma with a cytotoxic/suppressor immunophenotype. A brief review of the literature of primary brain T-cell lymphoma is also presented.
LIVER
Peripheral T-cell lymphoma arising in the liver.Stancu M, Jones D, Vega F, Medeiros LJ.
Division of Pathology and Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Am J Clin Pathol 2002 Oct;118(4):574-81 Abstract quote We report 3 cases of primary hepatic peripheral T-cell lymphoma (PTCL). All patients were men, 50 to 57 years of age, who sought care because of systemic symptoms including fever, fatigue, and weight loss. Physical examination revealed hepatomegaly in 2 patients, associated with jaundice in 1. Two patients had abnormal serum liver enzyme levels and coagulation profiles.
Imaging studies demonstrated marked hepatomegaly without focal lesions in 1 patient and multiple discrete tumor masses in 2 patients. Tumor infiltrates in biopsy specimens were heterogeneous with a large cell component in 2 cases. An inflammatory background was present in all cases, complicating the histologic recognition of PTCL Immunohistochemical studies showed that all tumors were of T-cell lineage, and 2 cases had monoclonal T-cell receptor gamma chain gene rearrangements. One patient died of disease shortly after diagnosis, and 2 patients treated with multiagent chemotherapy are in clinical remission with 12 and 84 months of clinicalfollow-up, respectively.
PTCL may rarely arise in the liver. These neoplasms respond to chemotherapy, suggesting that this disease is curable if diagnosed at an early stage.
PARATESTICULAR Extranodal peripheral T-cell lymphoma with angiocentric growth pattern and Epstein-Barr viral DNA associated affecting paratesticular soft tissue
AnaPérez-Vallés, VicenteSabater-Marco, DominicaCarpio-Máńez, RafaelBotella-Estrada, EnriqueNogueira-Vázquez and MiguelMartorell-Cebollada
J Cutan Pathol 2000;27 (2), 80-86 Abstract quote
Peripheral T-cell lymphomas are uncommon, accounting for only 10% to 15% of all non-Hodgkin lymphomas and their classification has been controversial.
We report a case of peripheral T-cell lymphoma with angiocentric growth pattern which presented as a paratesticular tumoral nodule in a 47-year-old-man. Formalin-fixed paraffin-embedded samples from the paratesticular tumor and non-infiltrated adjacent tissue were submitted to histological, immunohistochemical, polymerase chain reaction (PCR)-based and in situ hybridization analysis.
Histopathologically, there was a lymphomatous infiltrate in the paratesticular soft tissue, composed of a variable mixture of medium-sized to large cells with large cytoplasm and irregular-shaped nuclei, together with blood vessel destruction, necrosis and karyorrhexis.
Immunohistochemical study revealed a high p53 expression in neoplastic cells that showed T cytotoxic immunophenotype, failing to express the natural killer (NK)-cell antigen CD56. A monoclonal rearrangement of the T-cell receptor (TCR) g gene by a PCR technique was demonstrated. Type-A Epstein-Barr Virus (EBV) DNA was detected by PCR-based analysis. A combined in situ hybridization and immunohistochemical study revealed that most cells labeled positive for EBV RNA showed immunostaining with the CD45RO antibody.
Based on the above results, the case reported was classified as extranodal peripheral T-cell lymphoma with cytotoxic phenotype and EBV associated. The present case does not fit neatly into any of the specific types of peripheral T-cell lymphomas of the REAL classification, so a diagnosis of peripheral T-cell lymphoma unspecified was made.
UTERUS Primary Endometrial T-Cell Lymphoma A Case Report
Cheryl M. Kirk, etal.
Am J Clin Pathol 2001;115:561-566 Abstract quote
Primary lymphomas of the female genital tract are rare. Most involve the cervix rather than the uterine corpus. All of those previously reported have been B-cell lymphomas, with the exception of 1 case report of an endometrial T-cell lymphoma in a Japanese woman.
We report the case of a white woman from the United States with a diffuse large cell lymphoma of the endometrium, characterized as a peripheral T-cell type on the basis of immunophenotypic and molecular probe studies. Staging evaluation revealed tumor limited to the endometrium (stage IE). The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection and received 6 cycles of combination chemotherapy, after which she remained free of disease at last follow-up of 36 months. Unusual features of this lymphoma case are discussed, with emphasis on differential diagnosis and speculation on histogenesis.
This case illustrates that, while most peripheral T-cell lymphomas are widely disseminated at presentation, those limited to a single extranodal site may have a favorable outcome akin to that associated with high-grade extranodal B-cell lymphomas of early stage.
HISTOLOGICAL TYPES CHARACTERIZATION General In general, there is little distinguishing histologic features between the different clinical entities
Diffuse or sinusoidal population of atypical lymphocytes, varying from small to large
Mixed inflammatory cell infiltrate with eosinophils, plasma cells, histiocytes, and small lymphocytes Adult T cell leukemia/lymphoma (HTLV-1) Peripheral blood contains hyperlobated neoplastic cells
Lymph node with pleomorphic mixture of small and large cellsAngioimmunoblastic T-cell lymphoma (AILD) Diffuse effacement of lymph node with increase in high endothelial venules and overall lymphocyte depleted appearance
Large intercellular deposits fo PAS positive material
May have high content of epithelioid cells, sometimes with clear cytoplasmHepatosplenic T-cell lymphoma Neoplastic cells infiltrate the red pulp of the spleen and liver sinusoids
Lack CD5 and CD7 antigensEnteropathy type T-cell lymphoma
(Intestinal T-cell lymphoma)Diffuse involvement of the epithelium and adjacent mucosa
CD103 positiveAnaplastic Large Cell lymphoma (CD30+) T-cell lymphoma with high content of epithelioid histiocytes (Lymphoepithelioid lymphoma, Lennert's lymphoma) Epithelioid histiocytes and polymorphic collection of inflammatory cells CD4+ Peripheral T-Cell Lymphoma With Follicular Involvement and a CD4+/bcl-6+ Phenotype Am J Surg Pathol 2001;25:395-400
A truly follicular pattern is thought to be restricted to B-cell lymphomas. We observed a prominent follicular growth pattern in three cases of nodal peripheral T-cell lymphomas, of which two were initially diagnosed as follicular lymphomas.
All three patients were male, ranged in age from 50 to 70 years, and had generalized lymphadenopathy at the time of diagnosis.
The follicles were sharply demarcated in two cases and large and vague in one case; in all cases, they contained abundant follicular dendritic cells. Neoplastic cells were small to medium, with irregular cleaved or round nuclei and clear cytoplasm, which was abundant in one case. Lymphoma cells in all cases were CD4+ CD8– CD57– bcl-6, with CD10 coexpression in 2 cases. Clonal rearrangement of the gamma chain of the T-cell receptor gene was demonstrated in each case.
Conclusions:
These cases expand the differential diagnosis of lymphomas with a follicular growth pattern and suggest that neoplastic T cells may have the capacity to induce or home to follicular structures.CD20+ Peripheral T-Cell Lymphoma with Aberrant Expression of CD79a and CD20: A Diagnostic Pitfall Mod Pathol 2001;14:105-110
A case of peripheral T-cell lymphoma with aberrant expression of B-cell–associated antigens L-26 (CD20) and mb-1 (CD 79a) is described. The disease pursued an aggressive clinical course, and the patient died of disease 6 weeks after presentation.
Results:
Immunohistochemical studies demonstrated expression of both T- and B-cell–associated antigens, including CD3, CD8, CD43, TIA-1, CD20, and CD79a. Other markers expressed by the tumor cells included CD56 and S-100. Of interest, ßF-1 staining for the ß chain of T-cell receptor (TCR) complex was positive in the small admixed T lymphocytes but was negative in the tumor cells, raising the possibility of a / T-cell lymphoma. Molecular studies by polymerase chain reaction (PCR) demonstrated clonal TCR- chain gene rearrangement without evidence for a clonal rearrangement of the immunoglobulin heavy chain gene. PCR for HHV-8 related sequences was negative. Mb-1 is an IgM-associated protein that was thought to be restricted to normal and neoplastic B cells. Although its coexpression has been reported in up to 10% cases of precursor T-cell lymphoblastic lymphoma, the coexpression of both CD20 and CD79a has not been described in mature T-cell malignancies. Biphenotypic lymphomas associated with HHV-8 have been reported in immunodeficiency, but no evidence of immune deficiency was identified, and studies for EBV and HHV-8 were negative.Conclusion:
This case illustrates that no marker has absolute lineage specificity and that immunophenotypic studies should always be performed with panels of monoclonal antibodies. Moreover, cases with ambiguous phenotypes may require genotypic studies for precise lineage assignment.CD20+ positive PTCL-occurring after case of nodular sclerosis Hodgkin's disease Mod Pathol 2000;13:1244-1252
Rarely may occur-T cell origin confirmed by PCR gene rearrangementCYTOTOXIC T-CELL CD8+ Spontaneously Relapsing Clonal, Mucosal Cytotoxic T-Cell Lymphoproliferative Disorder Case Report and Review of the Literature
Erik A. Ranheim, M.D., Ph.D.; Carol Jones, B.S.; James L. Zehnder, M.D.; Roger Warnke, M.D.; Alan Yuen, M.D.
From the Departments of Pathology (E.A.R., C.J., J.L.Z., R.W.) and Internal Medicine (J.L.Z., A.Y.), Stanford University Medical Center, CA, U.S.A.
Am J Surg Pathol 2000;24:296-301 Abstract quote
Primary T-cell lymphoma of the gastrointestinal tract is a rare and usually aggressive disorder that may be associated with celiac disease.
The authors describe a unique case of a clonal proliferation of CD8+ T cells involving the oral mucosa, ileum, and colon of a 35-year-old man that has regressed spontaneously and recurred numerous times over a 9-year period without treatment.
The patient's symptoms were limited to occasional rectal bleeding and recurring painful oral ulcers. Within the intestine, these collections of small T cells induced minimal architectural distortions and did not show extensive epitheliotrophism. Polymerase chain reaction and sequencing analyses revealed that the identical T-cell clone has been present for more than 9 years and in different mucosal locations in this patient.
This may represent a unique T-cell lymphoproliferative process akin to a mucosal counterpart of lymphomatoid papulosis of the skin.
Nodal CD8 positive cytotoxic T-cell lymphoma: a distinct clinicopathological entity.Mukai HY, Hasegawa Y, Kojima H, Okoshi Y, Takei N, Yamashita Y, Nagasawa T, Mori N.
Division of Hematology (HYM, YH, HK, YO, NT, TN), Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Mod Pathol 2002 Nov;15(11):1131-9 Abstract quote We studied 11 cases of nodal cytotoxic T-cell lymphoma, which express the CD8+ phenotype and cytotoxic molecules (T-cell intracellular antigen-1, granzyme B and perforin), to characterize the clinicopathologic spectrum of these neoplasms. The 11 cases consisted of four men and seven women, aged 5 to 82 years (mean, 53 years).
All cases were nodal, and eight of 11 had extranodal involvement, the most common being in bone marrow (eight cases) and liver (six cases). The expression of these cytotoxic molecules has been reported in some T/natural killer cell lymphomas mostly involved in extranodal sites of skin, nasopharyngeal region, or gastrointestinal tracts, but these types of extranodal involvement were rare in our cases.
Morphologically these lymphomas could be divided into two groups. One group (n = 6) showed a diffuse large cell type and massive necrosis or apoptosis that was accompanied by disseminated intravascular coagulation (DIC) or hemophagocytic syndrome (HPS) on the initial. The prognosis of this group was generally poor (survival = 1-19 months, median = 5 mo), and four of these six cases were fulminant. The other group (n = 5) showed a diffuse medium or mixed cell type, and the prognosis was not so poor (median survival = 17 mo).
Our results suggest that these nodal cytotoxic T-cell lymphomas originated from activated cytotoxic T-cells and were highly accompanied with DIC or HPS.
FOLLICULAR
- Peripheral T-cell lymphoma with a "follicular" pattern and the perifollicular sinus phenotype.
Jiang L, Jones D, Medeiros LJ, Orduz YR, Bueso-Ramos CE.
Department of Pathology and Laboratory Medicine, the University of Texas-Houston Medical School.
Am J Clin Pathol. 2005 Mar;123(3):448-55. Abstract quote
We report a case of peripheral T-cell lymphoma (PTCL) with an exclusively "follicular" pattern at one lymph node site and a diffuse pattern at a second lymph node site. Molecular studies confirmed the clonal identity of the tumor at both sites. In the lymph node showing a follicular pattern, the tumor cells appeared to infiltrate follicles where the perifollicular sinuses remained patent. The infiltrated follicles retained nonneoplastic B cells and a follicular dendritic cell network.
By contrast, in the lymph node showing diffuse involvement, intranodal sinuses were no longer identifiable and there was no evidence of tumor cells infiltrating follicles. The tumor immunophenotype was influenced by the pattern: the follicular component was positive and the diffuse component was negative for bcl-6 and CD31.
We suggest that the follicular growth pattern in this case of PTCL arose secondarily to tumor spread via the perifollicular sinus.PROLYMPHOCYTIC LEUKEMIA
BACKGROUND: T-cell prolymphocytic leukemia (T-PLL), formerly categorized as T-cell chronic lymphocytic leukemia, is a rare and aggressive hematologic malignancy. Although the skin is characteristically involved, it is not a well-recognized entity in the dermatologic literature.
METHODS: Six cases of cutaneous T-PLL are presented from a clinical, light microscopic, and phenotypic perspective.
RESULTS: The patient population comprised 2 women and 4 men, with a mean age of 69.8 years. The disease was associated in all with skin involvement with facial preference; edema, purpura, and lesional symmetry were characteristic. The skin biopsies demonstrated a largely non-epidermotropic angiocentric lymphocytic infiltrate with accompanying hemorrhage. The cells showed irregular- to reniform-shaped nuclei with small nucleoli and eosinophilic rims of cytoplasm. Phenotypic studies revealed three prevailing profiles: CD4 dominant in 4, CD8 dominant in one, and co-expression of CD4 and CD8 in one. CD3 loss was seen in one case. All expressed T-cell leukemia 1 (TCL-1) and CD7; cutaneous lymphocyte antigen expression was discernible in a dot-like perinuclear array. All cases tested excluding one expressed TCL-1 and CD52. In two cases tested, T-cell receptor beta rearrangements were observed. Cytogenetic studies demonstrated a paracentromeric chromosome 14 inversion. Polysomy 8 and MYC amplification was seen in one case, manifesting an aggressive clinical course. Four patients died from their disease within 18 months of diagnosis.
LIMITATIONS: Cytogenetic MYC amplification, FISH, and TCR beta studies were conducted on each of 2 cases, respectively, due to limitations of tissue block samples and/or peripheral blood. cMYC translocation studies were conducted on 3 of the 6 cases, again due to limitations imposed by the tissue samples on the cases. The last case was recently diagnosed and, therefore, long-term follow-up is not possible.
CONCLUSION: T-PLL is a distinctive post-thymic T-cell malignancy with frequent cutaneous tropism. A diagnosis is possible in almost all cases based on characteristic clinical, light microscopic, phenotypic, and cytogenetic features. While a chromosome 14 inversion is highly characteristic, additional inherent cytogenetic differences, such as trisomy 8 with CMYC over-amplification, may account for some case to case variation in clinical course.
SPECIAL STAINS/
IMMUNO-
PEROXIDASECHARACTERIZATION Immunophenotypic Analysis of Peripheral T-Cell Neoplasms A Multiparameter Flow Cytometric Approach
Saba Jamal, MD
Louis J. Picker, MD
Deborah B. Aquino, MD
Robert W. McKenna, MD
D. Brian Dawson, PhD
Steven H. Kroft, MDAm J Clin Pathol 2001;116:512-526 Abstract quote
We retrospectively reviewed multiparameter flow cytometric analyses in 50 peripheral T-cell neoplasms (PTCNs).
Results were interpreted within the context of a large cohort of nonneoplastic T-cell populations. All PTCN diagnoses were confirmed with morphologic and/or molecular analysis. Aberrant populations were defined as discrete immunophenotypic clusters exhibiting loss of or increased or diminished expression of T-cell antigens relative to internal immunophenotypically normal T-cell populations. An antigenic pattern was considered abnormal if it exceeded ranges for T-cell subsets in specific anatomic sites or was not normally encountered. Forty-six of 50 and 41 of 50 demonstrated 1 or more and 2 or more aberrations, respectively. The most common abnormally expressed antigen was CD3, followed by CD7, CD5, and CD2. Except for CD7, abnormally dim or bright antigen expression was more common than deletion. Only 3 cases were abnormal solely based on expansion of an otherwise immunophenotypically normal population; the remainder had patterns of antigen expression not seen in nonneoplastic populations.
These data indicate that most PTCNs are aberrant by multiparameter flow analysis. However, results must be interpreted within the context of thorough knowledge of the immunophenotypic spectrum of nonneoplastic T cells.
Aberrant expression of T cell markers May show absence of one or more of pan-T cell markers:
CD2
CD3
CD5
CD7CD4 and CD8 Most are CD4+ CD8-
20% are CD4-CD8+1/6 of cases are CD4-CD8-
Rare cases CD4+CD8+CD3+, CD4+, CD8-, betaF1+, CD7-/+, TCRdelta- CD2+, CD3-/+ (cytoplasmic), CD5-, CD4/8-, EBER+, TIA-1+, betaF1-TCRdelta- CD3+, CD4+, CD8-, betaF1+, TCRdelta+ CD3+, CD4-, CD8+, TIA-1+, betaF1+, TCRdelta-(occasional cases +), CD56-/+, EBER- CD3+, CD4-, CD8-/+, betaF1-, TCRdelta+, TIA-1+, CD56+/-, EBER- CD3+, CD4-, CD8+, TIA+, EBER-, CD103+ CD3-/+, CD15-, CD30+, EMA+/-, ALK1+/-, EBER-, TIA1+/- CD3+/-, CD4>CD8, CD5+/-, CD7-/+, TIA1-/+ CD3+, CD7+, CD4-/+, CD8-/+, Tdt+ CD10
- CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells.
Reichard KK, Schwartz EJ, Higgins JP, Narasimhan B, Warnke RA, Natkunam Y.
1Department of Pathology, Stanford University Medical Center, Stanford, CA, USA.
Mod Pathol. 2006 Mar;19(3):337-43. Abstract quote
CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap.
Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13).
Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10(+) atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10(+) peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity.
The predominant staining pattern in the CD10(+) cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively.
This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.CD30 AND CD 15
Peripheral T-cell lymphomas expressing CD30 and CD15.
Barry TS, Jaffe ES, Sorbara L, Raffeld M, Pittaluga S.
Hematopathology Section, Laboratory of Pathology, National Cancer Intitute, National Institutes of Health, Bethesda, MD 20892, USA.
Am J Surg Pathol. 2003 Dec;27(12):1513-22. Abstract quote
Coexpression of CD30 and CD15 is typically associated with classic Hodgkin's lymphoma (HL). Peripheral T-cell lymphomas (PTCLs) can often display histologic features that simulate classic HL. However, reports of PTCLs coexpressing both CD30 and CD15 have been infrequently described.
We report 11 cases of PTCL in which at least a subset of the neoplastic cells coexpressed CD30 and CD15. The patients included 4 women and 7 men and age ranged from 43 to 83 years (median, 62 years). Nine of 10 patients had advanced stage III or IV disease at presentation. Nodal involvement predominated in 8 of 11 patients, whereas 2 patients presented primarily with skin involvement. Two distinct groups were identified based on morphologic and immunophenotypic features. The first group of 5 cases had histologic features mimicking classic HL with CD30+, CD15+ Reed-Sternberg (RS)-like cells in an inflammatory background of varied extent and composition. The background lymphoid cells showed minimal cytologic atypia. The RS-like cells were negative for CD20 and CD79a in all cases, and CD45 expression was absent in 4 of 5 cases. The RS-like cells expressed CD25 and at least one T-cell-associated marker in all cases. The background T-cell population showed convincing subset predominance in 4 of 5 cases and loss of T-cell-associated antigens in 3 of 5 cases and coexpression of CD30 and CD15 in one case. The second group of 6 cases had morphologic features more in keeping with PTCL than classic HL.
The proportion of neoplastic cells coexpressing CD30 and CD15 varied. Loss of T-cell antigens was noted in all cases and CD4 predominated in 4 of 5 cases. Three of the 6 cases expressed CD45. PCR analysis revealed clonal T-cell receptor gamma (TCR-gamma) chain gene rearrangements in 9 of 11 cases, but no immunoglobulin heavy (IgH) chain gene rearrangements. In situ hybridization studies for Epstein-Barr virus were negative in all cases. In some PTCL cases, the overlap with classic HL can be striking, and combined immunophenotypic and molecular studies are often necessary to confirm the diagnosis.CD69
CD69 expression correlates with expression of other markers of Th1 T cell differentiation in peripheral T cell lymphomas.Dorfman DM, Shahsafaei A.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Hum Pathol 2002 Mar;33(3):330-4 Abstract quote CD69, a marker of early T cell activation, is associated with Th1 T cell differentiation. Previously we found that peripheral T cell lymphomas could be subdivided based on the expression of markers of Th1 versus Th2 differentiation, including CXCR3, CD134/OX40, CCR4, and CD30.
Here we report immunohistochemical staining for CD69 in frozen and paraffin sections of peripheral T cell lymphomas that exhibit immunoreactivity for markers of Th1 or Th2 differentiation. CD69 expression correlated with immunoreactivity for other Th1 differentiation markers in 18 of 19 frozen specimens of peripheral T cell lymphomas (P = 0.0005). In 10 of these cases in which paraffin-embedded tissue was available for study, CD69 immunohistochemical staining of paraffin sections correlated with frozen section expression. CD69 immunostaining was performed on paraffin sections from 53 additional cases of peripheral T cell lymphoma and correlated with immunoreactivity for other Th1 differentiation markers (P < 0.0001) and was associated with specific subtypes of peripheral T cell lymphoma, including angioimmunoblastic lymphoma, Lennert's lymphoma, and mycosis fungoides/Sezary syndrome, previously noted to express Th1 differentiation-associated markers.
Anaplastic large cell lymphoma, both systemic and cutaneous, which typically exhibits immunoreactivity for markers of Th2 expression, was negative for CD69 immunostaining in 22 of 24 cases. CD69 immunostaining results support previous findings that a subset of T cell lymphomas exhibits immunophenotypic features of either Th1 or Th2 T cell differentiation. In addition, CD69 is a useful immunohistochemical marker for specific T cell lymphomas in frozen and paraffin-embedded tissue.
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Stage is best predictor of survival 5 Year Survival Median survival varies from 10-30 months CYTOTOXIC MOLECULE EXPRESSION
- Clinicopathologic and Prognostic Significance of Cytotoxic Molecule Expression in Nodal Peripheral T-Cell Lymphoma, Unspecified.
Asano N, Suzuki R, Kagami Y, Ishida F, Kitamura K, Fukutani H, Morishima Y, Takeuchi K, Nakamura S.
From the *Department of Pathology and Molecular Diagnostics, daggerDivision of Molecular Medicine, and double daggerDepartment of Hematology and Chemotherapy, Aichi Cancer Center, Nagoya; section signDepartment of Internal Medicine, Shinshu University School of Medicine, Matsumoto; parallelDepartment of Internal Medicine, Ichinomiya Municipal Hospital, Ichinomiya; paragraph signDepartment of Internal Medicine, Prefectural Aichi Hospital, Okazaki; and #Department of Pathology, Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan.
Am J Surg Pathol. 2005 Oct;29(10):1284-1293. Abstract quote
Cytotoxic molecules (CMs) are apoptosis-inducing molecules that are present in azurophilic cytoplasmic granules of T lymphocytes.
Expression of TIA-1 and granzyme B was examined for 100 cases of nodal peripheral T-cell lymphoma, unspecified (PTCL-U) to assess clinicopathologic significance of CM. Forty-one were positive for at least one CM. Patients with CM-positive PTCL-U showed younger onset (median, 55 years vs. 64 years, P = 0.01) and less male predominance (male:female ratio, 21:20 vs. 44:15, P = 0.02).
CM-positive PTCL-U was significantly associated with several clinical factors to indicate poor prognosis, in comparison with CM-negative PTCL-U, such as poorer performance status (P = 0.006), more frequent B-symptoms (68% vs. 35%, P = 0.002), higher serum lactate dehydrogenase levels (P = 0.003), and more frequent extranodal involvement, particularly bone marrow involvement (33% vs. 9%, P = 0.004). Epstein-Barr virus was mostly found in CM-positive PTCL-U (51% vs. 2%, P < 0.0001). The CM-positive group showed higher distribution of the International Prognostic Index (P = 0.009) and the Prognostic Index for T-cell lymphoma (P = 0.004) scores than CM-negative group. Complete remission rate was 30% for the former but 63% for the latter. Overall survival of CM-positive PTCL-U was significantly lower than that of CM-negative patients (P = 0.004). Multivariate analyses confirmed that CM expression is a significant prognostic factor, independent from other clinical factors or prognostic index scores.
These findings suggest that nodal CM-positive PTCL-U show distinct clinicopathologic characteristics among the current category of PTCL-U.Treatment Combination chemotherapy
Lower stage patients may be treated with radiation and surgery firstHenry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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