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ABSTRACT: Erythema nodosum (EN) is a cutaneous inflammatory reaction, usually reported in young women, but it is rarely observed among transplant patients. Localization in the lower extremities is typical, mostly involving the anterior surfaces of the legs. Several viral, bacterial, mycotic, and non-infectious etiologies, such as autommune disorders, drugs, inflammatory bowel diseases, sarcoidosis, pregnancy, and malignancies, have been found. We describe the case of a young woman kidney transplant recipient developing bilateral, erythematous, warm nodules localized on the anterior surface of her legs after antibiotic treatment for pneumonia with levofloxacin. Her immunosuppression was sirolimus and mycophenolate mofetil. EN was diagnosed by skin biopsy; microscopic examination showed septal panniculitis with granulomas. As a complete remission of the lesions was obtained in our patient after interruption of levofloxacin therapy, we suspect that levofloxacin was involved in the pathogenesis of EN. In fact, the management of EN is based on the treatment of underlying or associated conditions.
Transplant Infectious Disease 04/2011; 14(1):72-4. · 2.22 Impact Factor
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C Esposito,
F Grosjean,
M Torreggiani,
V Esposito,
F Mangione,
L Villa,
G Sileno, R Rosso,
N Serpieri,
M Molinaro,
G Fasoli,
A Dal Canton
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ABSTRACT: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses.
Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-β, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography.
Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 μl/min, p < 0.05; 126 ± 170 vs. 567 ± 374 μl/min, p < 0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-β expression and matrix deposition. Only sirolimus increased metalloprotease activity.
Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.
American Journal of Nephrology 02/2011; 33(3):239-49. · 2.54 Impact Factor
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M Lucioni,
E Boveri, R Rosso,
M Benazzo,
V Necchi,
M Danova,
P Incardona,
C Franco,
A Viglio,
R Riboni,
M Lazzarino,
U Magrini,
A Canevari,
M Paulli
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ABSTRACT: To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma.
A 70-year-old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, alpha1-antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In-situ hybridization for Epstein-Barr virus was negative.
We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.
Histopathology 01/2004; 43(6):583-91. · 3.08 Impact Factor
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Contact Dermatitis 04/2002; 46(3):183-4. · 3.51 Impact Factor
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ABSTRACT: Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin.
We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen.
We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.
Archives of pathology & laboratory medicine 06/2000; 124(5):709-11. · 2.58 Impact Factor
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ABSTRACT: Splenic cystic lymphangioma is a very rare condition, and is classified among cystic proliferations of the spleen. It is considered to be the result of a developmental malformation of the lymphatic system and can involve the spleen alone or be a part of multiorgan disease. It is usually seen in children, often found incidentally. We describe a case of cystic lymphangioma of the spleen in an elderly woman putting emphasis on the rarity of the case in old age, and on the problems of differential diagnosis with the other cystic proliferations of the spleen, in particular hydatid disease, in the absence of histologic information.
Haematologica 04/2000; 85(3):314-7. · 6.42 Impact Factor
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ABSTRACT: Reactive cutaneous angioendotheliomatosis (RCA) is an uncommon benign disease characterized by intravascular proliferation of endothelial cells. The observation of RCA in infants is exceedingly rare. We describe a case of RCA in a 3-month-old infant. The lesions were characterized by six small purpuric papules (1-2 mm in diameter), distributed on the thighs and neck. The general condition of the patient was good, with no lymphadenopathy, systemic involvement, or fever. The histopathologic features of a papule were characterized by the presence of cohesive aggregates of large mononucleated cells protruding into the lumina of dilated vessels and filling some of them completely. Neither an inflammatory infiltrate nor a proliferation of pericytes were present around blood vessels. Intravascular proliferating cells demonstrated positive staining for Ulex europaeus agglutinin 1 (UEA-1) and for Factor VIII-RA and CD34 antigens. The course of the disease was unremarkable with persistence of the lesions for 8 months; no treatment was started.
American Journal of Dermatopathology 03/1999; 21(1):42-5. · 1.20 Impact Factor
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M Paulli,
E Berti,
E Boveri,
S Kindl,
E Bonoldi,
C Gambini, R Rosso,
G Borroni,
V Straccapansa,
U Magrini,
J E DeCoteau,
P H Krammer,
P Möller,
M E Kadin
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ABSTRACT: The spectrum of CD30+ cutaneous lymphoproliferative disorders is characterized by the histology of a high-grade lymphoma but frequent clinical regression of skin lesions in lymphomatoid papulosis (LyP) and occasional regression in CD30+ large cell lymphomas (LCLs). A recent study shows that apoptosis may be a significant mechanism of regression of LyP (Arch Dermatol 133:828-833, 1997). Therefore, we studied expression of proteins that induce apoptosis, including CD27, CD40, CD95, and nerve growth factor receptor (NGF-R), as well as anti-apoptotic protein bcl-2 in skin lesions from 25 patients within the spectrum of CD30+ cutaneous lymphoma. Our results show consistent expression of CD95 (APO-1/Fas), but rare or absent expression of CD27, CD40, and NGF-R on tumor cells from both regressing LyP lesions and nonregressing CD30+ lymphomas. Bcl-2 was expressed at low levels in LyP and at high levels in pleomorphic CD30+ lymphomas. These results indicate that, in addition to CD30, CD95 expression is preferentially expressed at high levels in all cutaneous CD30+ lymphomas and suggest that CD95 may play a role in the regression of CD30+ skin lesions. Expression of bcl-2 appears to protect tumor cells from apoptosis in CD30+ lymphoproliferative disorders.
Human Pathlogy 12/1998; 29(11):1223-30. · 2.88 Impact Factor
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ABSTRACT: We report a case of primary neuroendocrine carcinoma of the skin (PNECS) mimicking a lymphoepithelioma-like carcinoma of the skin (LELCS) with respect to both cytomorphology and the presence of a dense lymphoplasmacytic stroma. The tumor occurred in the left forearm of a 86-year-old woman, and its history was marked by aggressive behavior, with metastases to lymph nodes and to visceral sites within 1.5 years of diagnosis. The neoplastic epithelial cells had an immunophenotypic profile typical of PNECS, reacting for cytokeratin 20 and other low-molecular weight cytokeratins, neuron-specific enolase, neurofilament protein, synaptophysin, and chromogranin A. In addition, they were immunoreactive for epithelial membrane antigen, carcinoembryonic antigen, and S-100 protein, as observed in LELCS of supposed adnexal differentiation. The tumor-infiltrating lymphocytes were mostly of T-lineage, with a predominance of CD8+ cells. We believe the case is a morphologic variant of PNECS, retaining its aggressive behavior and high metastatic potential, and should not be confused with true LELCS, which has a more favorable outcome. Immunohistochemistry is paramount in establishing the diagnosis. Lymphoid infiltration, even if prominent, does not seem to be of favorable prognostic significance in such a context.
American Journal of Dermatopathology 11/1998; 20(5):483-6. · 1.20 Impact Factor
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M Paulli,
M Lazzarino,
U Gianelli,
E Sträter,
E Orlandi,
C Klersy,
A Viglio, R Rosso,
M Gambacorta,
T Rousset,
E Morra,
T Lavabre-Bertrand,
C Bernasconi,
C Manegold,
U Magrini,
P Möller
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ABSTRACT: The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.
Leukemia and Lymphoma 01/1998; 26 Suppl 1:115-23. · 2.58 Impact Factor
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M Paulli,
E Boveri, R Rosso,
M Aricò,
S Kindl,
A Viglio,
E Berti,
F Leithäuser,
F Locatelli,
U Gianelli,
G Beluffi,
A C Feller,
G Borroni,
U Magrini
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ABSTRACT: We describe the clinicopathologic features of an unusual case of CD30+/CD50+ T-cell lymphoma in a child who presented with simultaneous primary extranodal cutaneous and bone localizations. The expression of CD56 (neural cell adhesion molecule, or NCAM) is rare in non-Hodgkin's lymphomas other than in a group of haematopoietic/lymphoid neoplasms of natural killer and natural killer-like T-cells, which usually involve extranodal sites and often pursue an aggressive clinical behavior. Coexpression of CD30 and CD56 in T-cell lymphomas is exceedingly rare, and its biological significance is unknown. Our patient responded well to an intensive chemotherapy regimen, and she is now in complete remission 4 years after discontinuation of chemotherapy. Expression of NCAM could be regarded as responsible, in part, for the extranodal localization of lymphoma cells; expression of CD56 also might contribute to the definition of a subset of CD30+ lymphomas with distinctive clinicopathologic features.
American Journal of Dermatopathology 09/1997; 19(4):384-90. · 1.20 Impact Factor
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Histopathology 08/1996; 29(1):78-80. · 3.08 Impact Factor
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ABSTRACT: Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease, is rare histiocytic disorder of known origin which shares several cell markers with Langerhans' cell histiocytosis (LCH). Although Rosai-Dorfman cells exhibit an aberrant immunophenotype, the indolent clinical course of SHML suggests a reactive disorder rather than a neoplastic process. Until recently this was prevailing opinion concerning LCH also, but recent studies have detected clonal histiocytes in all forms of this latter condition, which is therefore considered a clonal neoplastic disorder with highly variable biological behaviour. To determine whether the histiocytic proliferation in SHML is polyclonal or clonal we used X-linked polymorphic loci to assess clonality in lesional tissues in two women. Polymorphic regions of the human androgen receptor (HUMARA) locus were amplified by polymerase chain reaction (PCR) analysis. The HUMARA locus was informative in both cases and, following digestion with methylation-sensitive enzymes, typical polyclonal X-inactivation patterns were observed. Since abnormal cells accounted for > 90% lesional tissue cells, we conclude that Rosai-Dorfman histiocytic proliferation was polyclonal in the women studied.
British Journal of Haematology 11/1995; 91(2):415-8. · 4.94 Impact Factor
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ABSTRACT: This report describes a case of a malignant vascular tumor of the spleen with the morphologic, immunologic, and ultrastructural features observed in splenic sinus-lining cells (littoral cells). Histological examination showed a well-differentiated neoplasm forming ectatic blood channels with intraluminal papillary fronds. Tumor cells displayed malignant nuclear features and hemophagocytosis. Solid neoplastic areas with mitotic figures were present. Ultrastructurally, the tumor cells showed the concomitant presence of lysosomes and Weibel-Palade bodies. Immunohistochemically, the tumor cells were positive for both endothelial (Factor VIII-AG, CD34) and histiocytic markers (cathepsin D, lysozyme, alpha-1-antichimotrypsin). Our results indicate that angiosarcoma may originate from all the vascular compartments of the spleen, including red-pulp sinuses, and may have morphologic and immunophenotypic similarities to littoral cell angioma, a recently described benign vascular tumor of the spleen.
American Journal of Surgical Pathology 11/1995; 19(10):1203-8. · 4.35 Impact Factor
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ABSTRACT: Recently, it has been shown that CD30 antigen expression is associated with a relatively favorable prognosis in primary cutaneous large-cell lymphomas (CLCLs). However, prognostic subsets within the CD30+ group have been difficult to identify due to lack of uniform clinicopathologic and immunophenotypic criteria, limited clinical information, and the inclusion of relatively few patients for statistical analysis in prior studies. To address these problems, we formed a multicentric study group of pathologists and dermatologists to classify and evaluate 92 cases of CD30+ cutaneous lymphoproliferative disorders.
An expert panel established consensus diagnoses for 86 CD30+ cutaneous lymphomas. Cases, clinically and histologically classified as lymphomatoid papulosis (LyP), anaplastic large-cell lymphoma (ALCL), nonanaplastic lymphoma, and borderline histology between LyP and ALCL, were then analyzed statistically by univariate, multivariate, and Cox regression model analysis of potential prognostic features.
Spontaneous regression and age less than 60 years were associated with a favorable prognosis, while extracutaneous disease and age greater than 60 had a poor prognosis. Patients with LyP had the best prognosis, followed by those with primary CD30+ lymphomas, regardless of cytologic type (anaplastic or nonanaplastic). Borderline cases, morphologically indistinguishable from LyP and CD30+ ALCL, had a favorable prognosis, similar to LyP.
Our findings indicate that CD30+ cutaneous lymphoproliferative disorders comprise a spectrum of closely related skin lesions, which can be assigned a relatively favorable or unfavorable prognosis by a combined clinical and pathologic analysis.
Journal of Clinical Oncology 07/1995; 13(6):1343-54. · 18.37 Impact Factor
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ABSTRACT: A case of a vascular tumor clinically and pathologically consistent with acquired progressive lymphangioma (benign lymphangioendothelioma) in a 48-year-old woman is reported. The lesion appeared in the skin close to a mastectomy scar 3 years after surgery and radiotherapy for invasive ductal carcinoma. On histologic examination, it mimicked an aggressive vascular neoplasm because of its infiltrative pattern. However, follow-up studies confirmed the benign nature of the lesion, clinically and histologically. This case indicates that acquired progressive lymphangioma may follow radiotherapy and must be considered in the differential diagnosis of other vascular proliferations occurring in the skin of the breast, especially of low-grade postradiation angiosarcoma, a recently described neoplastic entity.
Journal of Cutaneous Pathology 05/1995; 22(2):164-7. · 1.56 Impact Factor
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ABSTRACT: Splenic marginal zone (MRZ) cell lymphoma is a recently described neoplasm arising in a unique compartment of splenic white pulp, producing massive splenomegaly and spreading to bone marrow and distant lymph nodes. We report three cases of splenic lymphoma that morphologically and immunohistochemically appear to originate from MRZ cells that presented as indolent neoplasms involving the spleen but with no or only moderate enlargement of the organ, presumably representing an early clinical stage of this disorder. Despite the evidence of involvement of the liver in one case, lymph nodes and bone marrow proved to be uninvolved. Histologically, the three spleens showed similar features, being characterized by the involvement of white pulp follicles and periarteriolar lymphoid sheaths by medium-sized lymphoid cells with slightly irregular nuclei and ample cytoplasm. Immunohistochemically, all the specimens expressed a series of B-lineage markers that, in contrast to specimens of monocytoid B cell lymphoma (MBCL) and hairy cell leukemia (HCL) studied for comparison, did not react with KiB3, LN1, and DBA.44 monoclonal antibodies.
Human Pathlogy 02/1995; 26(1):39-46. · 2.88 Impact Factor
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ABSTRACT: The authors report a single case of primary soft tissue CD30+ non anaplastic non-Hodgkin's lymphoma. The clinical, histological and immunohistochemical features of this peculiar lymphoma type are discussed. Within extranodal lymphomas, a primary soft tissue involvement is rare and the literature lacks exhaustive data on the clinical behaviour of these malignancies. In our case, the prognosis appeared more closely related to the clinical stage of the disease than to histology.
Pathologica 11/1994; 86(5):504-8.
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M. Paulli,
E. Boveri, R. Rosso,
U. Magrini,
E. Solcia,
A. C. Feller,
H. Merz,
S. Kindl,
E. Berti,
F. Facchetti,
C. Gambini,
F. Bonetti,
M. -L. Geerts,
P. Möller,
M. Samloff
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ABSTRACT: Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/1994; 424(6):601-606. · 2.49 Impact Factor
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ABSTRACT: The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and frequently involving the skin and other extranodal sites. In cutaneous large cell lymphomas, the CD30 expression was indicated as a favorable prognostic marker independently from cytology, anaplastic versus nonanaplastic. The stomach is the most common site of extranodal lymphomas in the adult population, but primary gastric CD30+ lymphomas have been reported rarely.
The clinical, morphologic, and immunohistochemical features of six cases with primary CD30/Ki-1+ gastric large cell lymphomas were analyzed.
The mean age of patients was 64 years with a prevalence of women (M:F ration = 1:2). Patients were assigned to Stage IE or IIE. Three of them died of disease, whereas the others are still alive (mean follow-up, 18 months). Three of six cases had ALCL morphology, whereas other cases had centroblastic, immunoblastic, and high-grade mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B-cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and a null, non-B, non-T phenotype in two of six cases.
Within CD30+ primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic, did not affect clinical presentation and/or prognosis. The survival rate of the patients studied is in keeping with literature reports regarding prognosis of primary high-grade gastric NHL. The findings suggest that clinical behavior of this extranodal lymphoma is more closely related to clinical symptoms and initial stage of disease than to CD30 expression.
Cancer 03/1994; 73(3):541-9. · 4.77 Impact Factor
