The impact of histopathologic examination of graft-versus-host disease in the era of reduced-intensity conditioning regimen: a study from the Gruppo Italiano Trapianto di Midollo Osseo.

Reduced-intensity conditioning regimens have reshaped the clinical presentation of graft-versus-host disease after hematopoietic stem cell transplants. However, histopathologic features of graft-versus-host disease following reduced-intensity conditioning regimens have not been fully characterized. In a series of 112 biopsies (skin, n = 60; gastrointestinal [GI] tract, n = 44; liver, n = 8), we described the morphologic profile of graft-versus-host disease following reduced-intensity conditioning and investigated whether histopathologic changes of graft-versus-host disease following reduced-intensity conditioning have a diagnostic and/or prognostic value. Forty-four patients (49.5%) experienced acute graft-versus-host disease, 2 (2.2%) late-onset acute graft-versus-host disease (grade I, n = 13; grade II-IV, n = 33), 24 (27.0%) chronic graft-versus-host disease (de novo n = 12, progressive n = 12) and 19 (21.3%) overlap syndrome. In the skin, we observed: (i) phase-nonspecific changes, such as acute graft-versus-host disease features in chronic graft-versus-host disease patients (n = 4/24; 16.6%), (ii) subtle alterations such as superficial fibrosis in widened dermal papillae (n = 8), in acute graft-versus-host disease/late-onset graft-versus-host disease (n = 6/46; 13.0%) or chronic graft-versus-host disease (n = 2/24, 8.3%) patients, and (iii) features of chronic and acute graft-versus-host disease coexisting in the same specimen in overlap syndrome (n = 3/19; 15.7%). In the GI tract, we did not demonstrate peculiar features differing from those commonly observed in the myeloablative setting. By univariate analysis, a reduced overall survival was associated with graft-versus-host disease type (chronic graft-versus-host disease P = .006, acute graft-versus-host disease P = .03), older age (P = .04), and histopathologic diagnosis of "consistent with" + definite graft-versus-host disease (P = .02). Histopathologic diagnosis retained an independent prognostic value by multivariate analysis (P = .01). The present study indicates that pathologists should be aware of the peculiar morphologic changes of cutaneous graft-versus-host disease following reduced-intensity conditioning and further recommends histopathology in the diagnostic workup of graft-versus-host disease in patients undergoing reduced-intensity conditioning regimen.

Primary high-grade B-cell lymphoma of the choroid plexus.

Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma arising from and confined to the neuraxis. It represents about 3-4% of all primitive brain neoplasms and is mainly located in deep supratentorial regions. A ventricular involvement is quite frequent, but in the vast majority of cases it is secondary to an extension from a subependymal location. Amongst the primary ventricular forms occasionally reported, a choroid plexus origin is extremely rare; to date, only three cases have been described in the English literature. We report the case of a 71-year-old left-handed woman admitted to our department after a progressive 2-week history of confusion, motor speech disturbances and left hemiparesis. A brain MRI scan displayed an intraventricular lesion located in the right atrium, about 2.5cm in its major axis, homogeneously enhancing after gadolinium administration, surrounded by edema in the homolateral deep hemispheric region; the main diagnostic hypothesis was meningioma. She underwent a parieto-occipital craniotomy and a navigation-assisted posterior parietal transcortical approach, achieving complete removal of the intraventricular lesion originating from the choroid plexus. The histological diagnosis was of high-grade diffuse large B-cell lymphoma. Both an MRI scan of the entire craniospinal axis and a thoracic and abdominal CT scan showed no other neoplastic lesions; a bone marrow biopsy was normal; a final diagnosis of primary central nervous system lymphoma was made. CSF cytological analysis did not show any signs of lymphoma dissemination. Adjuvant chemotherapy with methotrexate was administered, and at the last follow-up (26 months) our patient is clinically and radiologically disease-free. Primary choroid plexus lymphoma is a very rare tumor that should be included in the differential diagnosis of intraventricular neoplasms. It usually occurs in the lateral ventricles (with a predilection for the atrium) of adult people (>50 years of age), apparently with a male prevalence. Generally, the radiological picture mimics that of a meningioma, despite the fact that meningiomas usually reach a greater volume before clinical onset. Surgery is almost always necessary to obtain an adequate tissue sample and frequently leads to a radical removal of the lesion. Low-grade marginal zone B-cell, T-cell and high-grade diffuse large B-cell (present case) forms have been described. With a proper adjuvant therapy a relatively good outcome is observed.

Laminin-5 gamma2 chain immunohistochemistry facilitates the assessment of invasiveness and improves the diagnostic reproducibility of glandular lesions of the cervix uteri.

The aim of this study was to evaluate the influence of laminin-5 (LN-5) gamma2 chain immunohistochemistry on the assessment of invasiveness in cervical adenocarcinomas and its impact on the diagnostic reproducibility of glandular lesions of the cervix uteri. Immunohistochemistry with LN-5 gamma2 was performed on 30 cases, including 12 adenocarcinomas in situ (AISs), 5 AISs that were suggestive, albeit not conclusive, of infiltration (AIS+), 7 frankly invasive adenocarcinomas, and 6 nonneoplastic cases with reactive changes. Diagnostic agreement between 3 observers was evaluated by kappa statistics in routine histologic specimens and with the aid of LN-5 gamma2 immunohistochemistry. Laminin-5 gamma2 was expressed in 5 of the 12 AISs (41.6%), all AIS+ and invasive adenocarcinomas, and none of the reactive cases. Cytoplasmatic staining was detected at the invasion front of frankly invasive adenocarcinomas and in tumor buds of all AISs with minimal stromal infiltration. Overall, interobserver agreement was significantly improved by adding LN-5 gamma2 immunostains to the conventional slides (0.56 versus 0.86; P = .002). The difference in interobserver agreement further increased when including only AISs and AIS+ in the analysis (0.17 versus 0.72; P = .000). After immunohistochemical evaluation, the original AIS diagnosis was unanimously changed to adenocarcinoma with minimal stromal invasion in 3 of 12 cases (25%), whereas a discordant hematoxylin-eosin diagnosis turned into a concordant one in 10 of 13 cases (6 AISs, 2 AIS+, 2 adenocarcinomas; 76.9%). Immunohistochemistry with LN-5 gamma2 facilitates the assessment of the invasiveness of cervical adenocarcinomas and improves the interobserver agreement in glandular lesions of the cervix uteri.