TY  - JOUR
AB  - In this study, we sought to determine the prognostic value of both the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) score and the histologic parameters viable tumor, coagulative necrosis, hyalinization/fibrosis, and infarction in patients (n=64) with localized, nonmetastatic high-grade soft-tissue sarcomas after preoperative radiomonotherapy. A standardized macroscopic workup for pretreated surgical specimen including evaluation of a whole section of high-grade soft tissue sarcomas in the largest diameter, was used. Association with overall survival and disease-free survival was assessed. Limb salvage could be accomplished in 98.4% of patients. Overall, 90.6% tumors had negative resection margins. The median postoperative tumor diameter was 9 cm. Undifferentiated pleomorphic sarcoma (42.2%) and myxofibrosarcoma (17.2%) were the most common diagnoses. In all, 9.4% of patients had local recurrence despite clear resection margins, and 50% had distant metastases. Morphologic mapping suggests an overall heterogenous intratumoral response to radiotherapy, with significant differences among histologic subtypes. Complete regression (0% vital tumor cells) was not seen. Categorizing the results according to the proposed EORTC-STBSG 5-tier response score, <1% viable tumor cells were seen in 3.1%, ≥1% to <10% viable tumor cells in 20.4%, ≥10% to <50% viable tumor cells in 35.9% and ≥50% viable tumor cells in 40.6% of cases. Mean values for viable tumor cells were 40% (range: 1% to 100%), coagulative necrosis 5% (0% to 60%), hyalinization/fibrosis 25% (0% to 90%) and infarction 15% (0% to 79%). Hyalinization/fibrosis was a significant independent prognostic factor for overall survival (hazard ratio=4.4; P=0.047), while the other histologic parameters including the EORTC-STBSG score were not prognostic.
AU  - Boxberg, M.*
AU  - Langer, R.*
AU  - Woertler, K.*
AU  - Knebel, C.*
AU  - Rechl, H.*
AU  - von Eisenhart-Rothe, R.*
AU  - Weichert, W.*
AU  - Combs, S.E.
AU  - Hadjamu, M.*
AU  - Röper, B.*
AU  - Specht, K.*
C1  - 65444
C2  - 52684
SP  - 1060-1070
TI  - Neoadjuvant radiation in high-grade soft-tissue sarcomas: Histopathologic features and response evaluation.
JO  - Am. J. Surg. Pathol.
VL  - 46
IS  - 8
PY  - 2022
SN  - 0147-5185
ER  - 

TY  - JOUR
AB  - Initial treatment planning in esophageal squamous cell carcinoma mainly relies on clinical staging. Recently, a highly prognostic grading system based on the cellular dissociation parameters Tumor Budding and Cell Nest Size has been proposed for resected esophageal squamous cell carcinoma. To probe for the transferability and relevance of this established novel grading system in the pretreatment setting, we evaluated Tumor Budding/Cell Nest Size in pretherapeutic biopsies of either primarily resected (cohort 1, n=80) or neoadjuvantly treated (cohort 2, n=75) esophageal squamous cell carcinoma. Grading data were correlated with clinicopathologic and survival parameters. High Tumor Budding Activity and small Cell Nest Size in pretherapeutic biopsies were strongly associated with shortened overall survival, disease-free survival, and disease-specific survival in both cohorts. A modified histopathologic grading system incorporating both factors termed Cellular Dissociation Grade showed excellent prognostic demarcation between well (G1), moderately (G2), and poorly differentiated (G3) carcinomas in both scenarios (overall survival: cohort 1: P<0.001; cohort 2: P=0.009) and was predictive for a high pathologic tumor stage and the presence of nodal metastases in primarily resected patients. Multivariate analyses revealed the Cellular Dissociation Grade to be a predictor of poor outcome in the pretherapeutic setting independent of clinical stage (overall survival, disease-free survival, and disease-specific survival: P<0.001). Hazard ratio for disease-free survival was 3.19 for G2 and 5.66 for G3 carcinomas compared with G1 neoplasms. Our data not only prove the transferability of histopathologic grading based on Tumor Budding/Cell Nest Size to biopsy specimens in esophageal squamous cell carcinoma, but also demonstrate that the Cellular Dissociation Grade is a strong outcome predictor in this entity even in the pretreatment scenario. Therefore, we believe that this novel type of grading has the ability to serve as a powerful histology-based pretherapeutic biomarker, that might supplement clinical staging for choosing the most suitable therapy decision.
AU  - Jesinghaus, M.*
AU  - Brühl, F.*
AU  - Steiger, K.*
AU  - Klare, P.*
AU  - Reiser, M.*
AU  - Scheiter, A.*
AU  - Konukiewitz, B.*
AU  - Kühn, P.*
AU  - Münch, S.*
AU  - Quante, M.*
AU  - Schmid, R.M.*
AU  - Wilhelm, D.*
AU  - Feith, M.*
AU  - Friess, H.*
AU  - Combs, S.E.
AU  - Saur, D.*
AU  - Boxberg, M.*
AU  - Weichert, W.*
C1  - 55642
C2  - 46475
CY  - Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
SP  - 618-627
TI  - Cellular dissociation grading based on the parameters tumor budding and cell nest size in pretherapeutic biopsy specimens allows for prognostic patient stratification in esophageal squamous cell carcinoma independent from clinical staging.
JO  - Am. J. Surg. Pathol.
VL  - 43
IS  - 5
PB  - Lippincott Williams & Wilkins
PY  - 2019
SN  - 0147-5185
ER  - 

TY  - JOUR
AB  - We report a case of primary Epstein Barr virus (EBV) negative peripheral T-cell lymphoma (PTCL) NOS in a 56-year-old female who-after an initially indolent course - simultaneously developed an aggressive, EBV+ cytotoxic large T-cell lymphoma, clonally related to the primary PTCL, and an EBV+, clonal large B-cell lymphoproliferation. The initial, EBV-negative PTCL had shown some features of angioimmunoblastic T-cell lymphoma and had responded well to steroid therapy. Two years later, rapidly fatal, progressive disease with multivisceral involvement developed. Histologically, extensive infiltrates of EBV+, CD8(+) large cells were present, in addition to areas of the initial PTCL. Extensive comparative phenotypic and molecular analyses confirmed the presence of an identical CD8(+) T-cell clone in the initial EBV-negative PTCL and the EBV+, CD8(+) large cell lymphoma at the time of aggressive transformation. These results also justified the retrospective classification of PTCL, NOS for the initial lymphoma. This case shows that secondary EBV infection of an established malignant T-cell clone can occur and may contribute to aggressive transformation of PTCL.
AU  - Langer, R.*
AU  - Geissinger, E.*
AU  - Rudiger, T.*
AU  - von Schilling, C.*
AU  - Ott, G.*
AU  - Mandl-Weber, S.*
AU  - Quintanilla-Martinez, L.
AU  - Fend, F.*
C1  - 6145
C2  - 28242
CY  - Philadelphia
SP  - 1382-1387
TI  - Peripheral T-cell lymphoma with progression to a clonally related, Epstein Barr Virus plus, cytotoxic aggressive T-cell lymphoma: Evidence for secondary EBV infection of an established malignant T-cell clone.
JO  - Am. J. Surg. Pathol.
VL  - 34
IS  - 9
PB  - Lippincott Williams & Wilkins
PY  - 2010
SN  - 0147-5185
ER  - 

TY  - JOUR
AB  - The JAK2V617F mutation is an essential oncogenic event in Philadelphia negative chronic myeloproliferative disorders (Ph-cMPD). It is still unclear how a unique tyrosine kinase mutation can give rise to the broad clinical and morphologic spectrum of Ph-cMPD. One possible explanation could be differences in the JAK2V617F gene dosage, or different maturation stages on which myeloid lineages are affected by the mutation. The extent of lymphoid lineage involvement in JAK2V617F-positive cMPD is still controversial. We comparatively studied the zygosity status of microdissected megakaryocytes, nonmegakaryocytic hematopoietic cells, and reactive as well as neoplastic lymphoid nodules from bone marrow trephines of 61 patients with Ph-cMPD. The presence of the mutation and mutant gene dosage were determined by allele-specific polymerase chain reaction and TaqMan analysis, respectively. The mutation was detected in 22/32 (68%) cases of essential thrombocythemia, all cases of polycythemia vera, and 4/8 (50%) idiopathic myelofibrosis. Comparison of whole bone marrow sections and the different myeloid lineages showed similar percentages of the mutated allele. Restriction to a particular lineage or major differences in allele dosage were not observed, except for 2 cases in which megakaryocytes revealed a higher frequency of the mutated allele. A heterozygous JAK2V617F mutation was detected in 3/8 "reactive" lymphoid nodule in patients with Ph-cMPD, whereas all concomitant non-Hodgkin lymphoma of B-cell type were negative. These results demonstrate that different myeloid lineages usually show similar frequencies of the JAK2V617F allele. The occasional detection of JAK2V617F in benign lymphocytes points to involvement of the lympho-myeloid stem cell.
AU  - Kremer, M.*
AU  - Horn, T.*
AU  - Koch, I.*
AU  - Dechow, T.*
AU  - Gattenloehner, S.*
AU  - Pfeiffer, W.*
AU  - Quintanilla-Martinez, L.
AU  - Fend, F.*
C1  - 135
C2  - 25384
SP  - 928-935
TI  - Quantitation of the JAK2V617F mutation in microdissected bone marrow trephines: Equal mutational load in myeloid lineages and rare involvement of lymphoid cells.
JO  - Am. J. Surg. Pathol.
VL  - 32
IS  - 6
PB  - Lippincott Williams & Wilkins
PY  - 2008
SN  - 0147-5185
ER  - 

TY  - JOUR
AB  - Rare cases of CD20+ T-cell lymphoma (TCL) have been reported, but the clinicopathologic spectrum of this disorder is not known. We identified 9 cases of CD20+ TCL diagnosed at our institution and 26 additional cases through a search of the English language literature. Among current cases, there were 7 men (ages 71 to 81, median 75 y) and 2 women (ages 36 and 37 y). Five patients presented with predominantly nodal disease (localized in 3 and widespread in 2 cases) and 4 patients presented with purely extranodal disease involving the parotid glands, skin, or small intestine. CD20 was uniformly and strongly expressed in 5 cases and dimly expressed or present on a subset of neoplastic cells in 4 cases. The proportion of CD20+ T cells changed over time in 3 cases. Three cases fulfilled diagnostic criteria for clinicopathologically defined subtypes of TCL (2 mycosis fungoides; 1 enteropathy-type TCL), whereas 6 were peripheral TCL unspecified with variable cytomorphology, T-cell immunophenotype, and sites of involvement. In 8 of 9 cases, a clonal T-cell population was identified by molecular genetic analysis. Among 8 cases with clinical follow-up, 5 behaved aggressively with death from disease within 3 years of diagnosis in 4 cases (median survival: 11 mo, range: 1 to 35 mo), and recurrent disease at 10 months in 1 case; 1 patient died of an EBV+ B-cell lymphoma (BCL) 66 months after the original diagnosis; in the remaining 2 cases, patients were alive and undergoing treatment (follow-up: 4 and 18 mo). Historical cases showed similar clinicopathologic variability. CD20+ TCL is rare, and clinically and pathologically heterogeneous. When CD20 expression is present in TCL, it may be dimmer than that of normal B cells, suggesting neoplastic transformation of a normal CD20dim+ T-cell subset. Cases of CD20+ TCL in which the proportion of CD20+ cells changes over time may reflect aberrant expression of CD20, possibly as an activation marker, by neoplastic T cells. CD20+ TCL may cause diagnostic difficulty, particularly in cases that clinically and pathologically mimic BCL. Knowledge of the unusual phenomenon of CD20 expression in TCL, in conjunction with careful morphologic analysis, the use of a panel of antibodies, and molecular genetic studies, is important in avoiding a misdiagnosis of BCL.
AU  - Rahemtullah, A.*
AU  - Longtine, J.A.*
AU  - Harris, N.L.*
AU  - Dorn, M.*
AU  - Zembowicz, A.*
AU  - Quintanilla-Fend, L.
AU  - Preffer, F.I.
AU  - Ferry, J.A.*
C1  - 3527
C2  - 25810
SP  - 1593-1607
TI  - CD20+ T-cell lymphoma: Clinicopathologic analysis of 9 cases and a review of the literature.
JO  - Am. J. Surg. Pathol.
VL  - 32
IS  - 1
PB  - Lippincott Williams & Wilkins
PY  - 2008
SN  - 0147-5185
ER  - 

TY  - JOUR
AB  - Approximately 5% of B-cell chronic lymphocytic leukemia (B-CLL) patients develop a secondary aggressive lymphoma, usually of diffuse large B-cell type (DLBCL), termed Richter's transformation (RT). Rarely, classic Hodgkin lymphoma (HL) is observed. Published small series suggest that tumor cells in DLBCL and HL can be clonally identical to the B-CLL clone or arise as an independent, secondary lymphoma. We describe the morphology, immunophenotype, and clinical features of 34 classic RT patients with DLBCL, 6 cases of B-CLL with HL, and 8 cases with scattered CD30-positive Hodgkin and Reed-Sternberg (HRS)-like cells. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes. In classic RT, 18/23 B-CLL cases (78%) showed clonal progression to DLBCL with identical IgVH sequences in both lymphoma components, whereas in 5 cases (22%) the DLBCL was clonally unrelated. Among clonally related RT samples, 73% carried unmutated IgVH genes, whereas 4/5 unrelated cases were mutated. Immunophenotypically, most cases of DLBCL irrespective of clonal relatedness showed significant differences in phenotype compared with the B-CLL, with common loss of CD5 and CD23. Using immuno-laser capture microdissection, sequencing of the IgVH CDR3 region of isolated HRS cells showed that 2/2 cases with HL were clonally unrelated, whereas they were clonally identical in 1/2 cases of B-CLL with scattered HRS-like cells. HRS or HRS-like cells in all 3 unrelated cases showed evidence of Epstein-Barr virus infection. Of interest, 5/6 cases of B-CLL with HL, and 5/6 cases of B-CLL with HRS cells showed mutated IgVH genes.
AU  - Mao, Z.*
AU  - Quintanilla-Martinez, L.
AU  - Raffeld, M.*
AU  - Richter, M.
AU  - Krugmann, J.*
AU  - Burek, C.*
AU  - Hartmann, E.*
AU  - Rudiger, T.*
AU  - Jaffe, E.S.*
AU  - Müller-Hermelink, H.K.*
AU  - Ott, G.*
AU  - Fend, F.*
AU  - Rosenwald, A.*
C1  - 3276
C2  - 24642
SP  - 1605-1614
TI  - IgVH mutational status and clonality analysis of Richter's transformation: Diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution.
JO  - Am. J. Surg. Pathol.
VL  - 31
IS  - 10
PB  - Lippincott Williams & Wilkins
PY  - 2007
SN  - 0147-5185
ER  -