Renato Rosso

Immunophenotypic characterization of the cell infiltrate in five cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

Little is known about the nature of the large intrasinusoidal cells exhibiting cytophagocytosis, which are the histologic hallmark of sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease). Using a broad panel of monoclonal and polyclonal antibodies, we analyzed the immunophenotype of the cell infiltrates in seven lymph node biopsy specimens from five cases of SHML. The SHML cells constantly expressed the S-100 protein, concanavalin agglutinin and peanut agglutinin lectins, and monocyte-macrophage-associated antigens CD 11c, CD 14, CD 33, CD 68, and LN 5. Labeling with other antimacrophage antibodies was extremely variable, with some (MAC 387, lysozyme) restricted to clusters of SHML cells and others (CD11b, CD 36, alpha-1-antichymotrypsin) staining only scattered cells. The CD 1a antigen was found on some cells in only one case, whereas HLA-DR and the HLA-DR-associated invariant chains were absent. The heterogeneity of SHML cell marker expression might be related to the local content of factors (eg, cytokines) capable of modulating the phenotype of monocytes and derived cells. All cases presented with huge amounts of medium-sized mononuclear cells accumulated in the sinuses and intersinusoidal tissue. These cells expressed the S-100-/CD 11b+/CD 11c+/CD 14+/CD 16+/CD 33+/CD 36+/lysozyme+/MAC 387+/HLA-DR+ phenotype. These recently immigrated monocytes might represent the immediate precursors of SHML cells.

Littoral cell angiosarcoma of the spleen: case report with immunohistochemical and ultrastructural analysis

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.

Acquired progressive lymphangioma of the skin following radiotherapy for breast carcinoma

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.

Anaplastic large cell lymphoma, CD30/Ki-1 positive, expressing the CD15/Leu-M1 antigen. Immunohistochemical and morphological relationships to Hodgkin's disease.

In this report we analyze the morphological and immunohistochemical findings observed in 5 cases of CD30/Ki-1 positive anaplastic large cell lymphoma, a recently recognized neoplastic entity. In comparison with the Ki-1 lymphomas so far described, these cases showed a fairly large number of Reed-Sternberg-like cells, often admixed with small lymphocytes and occasional eosinophils. Moreover, in all our cases immunohistochemical reactions detected the CD15/ Leu-M1 antigen, together with markers of the T-lineage and of lymphoid activation. In previous studies the CD15/Leu-M1 antigen has been found in the majority of cases of Hodgkins disease, but has been stated to be absent typically in Ki-1 lymphomas. Our results indicate that this antigen cannot be considered a reliable tool to distinguish between Ki-1 lymphomas and Hodgkins disease. Furthermore, the morphological and immunohistochemical findings reported suggest that in some cases Ki-1 cell lymphoma and Hodgkins disease may be closely related. They may represent different steps in the progression of the same lymphoproliferative disorder.

Paederus fuscipes dermatitis: A histopathological study

Paederus fuscipes (PF) dermatitis is a self-healing blistering disorder of the skin caused by a small insect belonging to genus Paederus, family Staphylinidae, order Coleoptera. Crushing PF on the skin causes acute dermatitis within 24 hours, corresponding in shape and dimensions to the area affected by the substance released (pederin). The acute vesicular lesions become crusted and scaly within a few days and heal completely in 10–12 days, with a transitory postinflammatory hypercromic patch. Twenty consecutive cases of PF dermatitis at different stages were studied histologically by routine light microscopy. The pederin causes a spectrum of histopathologic changes ranging from acute epidermal necrosis and blistering in acute stages, to marked acanthosis with mitotic figures in the late stages. PF dermatitis is an entomological model of irritant contact dermatitis, having histopathologic features of intraepidermal and subepidermal blistering, epidermal necrosis and acantholysis. The presence of some acantholytic foci, relatively far from the foci of clinically involved skin, in four of the cases considered suggests a possible role of pederin in inducing acantholysis indirectly. Acantholysis is probably caused by the release of epidermal proteases.

The Ron proto-oncogene product is a phenotypic marker of renal oncocytoma

The proto-oncogene product Ron is the receptor for macrophage stimulating protein, a scatter factor that stimulates cell proliferation, prevents apoptosis, and induces an invasive cell phenotype. We investigated the expression of Ron, Ki-67 (proliferation index), p53, and bcl-2 (proapoptotic and antiapoptotic proteins, respectively) in 50 renal tumors (19 clear cell carcinomas, 18 oncocytomas, 7 papillary cell carcinomas, 5 chromophobe cell carcinomas, and 1 carcinoma with sarcomatoid areas). In addition, we studied Ron in normal kidney and in the renal carcinoma cell line Caki-1. Immunostaining and Western blot showed Ron in normal kidney and in all oncocytomas but never in renal cell carcinomas or in Caki-1. In addition, Western blot showed that Ron was expressed in phosphorylated, i.e., active, form. Bcl-2 was strongly expressed in oncocytomas, whereas Ki-67 and p53 were much less expressed in oncocytomas than in carcinomas. These results indicate in Ron a marker that differentiates oncocytoma from the other renal epithelial tumors. We therefore think that Ron may prove to be a new tool for a sound and precise diagnosis of oncocytoma, a benign tumor that cannot always be distinguished from carcinomas at histologic examination. The overexpression of bcl-2, but not p53 in oncocytoma, suggests that the MSP/Ron system sustains the growth of oncocytoma by opposing apoptosis.

Clinicopathologic and immunologic characteristics of non‐Hodgkin's lymphomas presenting in the orbit. A report of eight cases

Of 325 consecutive cases of non‐Hodgkins malignant lymphomas, 8 patients (2.4%) showed orbital presentation. The clinicopathologic and immunologic analysis of the eight patients revealed characteristic biologic features. Despite the apparently isolated orbital presentation, all cases had subclinical systemic disease. Seven of the eight cases exhibited lymphoplasmacytic/cytoid features, with concurrent type II cryoglobulinemia in five of them. In addition, during their clinical course, five patients showed single or multiple subcutaneous nodules with the same histologic and immunologic pattern as the orbital tumor. This study demonstrates that most orbital lymphomas share particular clinicopathologic and immunologic features, suggesting an origin from a B‐cell subset with preferential homing to orbital tissues and subcutis.

Cutaneous CD30+ lymphoproliferative disorders: expression of bcl-2 and proteins of the tumor necrosis factor receptor superfamily

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.

Relapsing eruptive multiple Spitz nevi or metastatic Spitzoid malignant melanoma

An unusual case of multiple relapsing Spitz nevus (SN) in a patient with pseudohypoparathyroidism is described. It arose initially as a single lesion, and recurred twice as multiple agminated lesions that maintained the same histological pattern as the original SN. Nevertheless, the clinical behavior led to a diagnosis of metastasis from malignant melanoma at another medical institution. This case emphasizes the need for relying on accurate histopathological criteria to distinguish SN from malignant melanoma if inappropriate and detrimental therapeutic procedures are to be avoided.

Reactive angioendotheliomatosis in an infant

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.