Guido Collina

Frequency and Distribution of Herpesvirus-like DNA Sequences (KSHV) in Different Stages of Classic Kaposi's Sarcoma and in Normal Tissues from an Italian Population

The frequency and distribution of herpesvirus‐like DNA sequences (KSHV) were investigated by PCR in the pathologic skin lesions of a series of 22 HIV‐negative elderly patients with classic Kaposis sarcoma (KS) from Italy, one of the few regions of the world where classic KS is prevalent. Viral sequences were clearly identifiable in 15 cases, in particular in 2 of 5 patch, in 3 of 6 plaque and in 10 of 11 nodular lesions. Our findings confirm the association of these herpesvirus‐like DNA sequences with KS in unrelated populations, providing evidence of the putative KS‐associated agent in all different histologic lesions of the disease, mainly in the nodular stage. The search for other herpesviruses by PCR showed that Epstein‐Barr virus (EBV) sequences were present in 7 of 22 pathologic skin lesions. In 4 cases, both EBV and KSHV were present. On the contrary, all 22 classic KS specimens were negative for human herpesvirus‐6 sequences. Two of 3 patch and the 1 nodular lesions from AIDS‐related KS patients examined were positive for KSHV but negative for both EBV and HHV‐6 sequences. Furthermore, we evaluated the prevalence of KSHV sequences in the normal population of the same geographical area. Thirteen peripheral blood mononuclear cell samples, 9 salivary gland tissues and 6 saliva samples from healthy subjects were invariably found negative for KSHV, using the same PCR technique. Of interest, 2 of 11 hyperplastic tonsils harboured these herpesvirus‐like sequences, suggesting that, like other herpesviruses, the KS‐associated agent may be harboured in a proportion of normal individuals and tonsils may represent at least one of the possible reservoirs of this putative lymphotropic γ‐herpesvirus in vivo.

Detection of human papillomavirus in extragenital Bowen's disease using in situ hybridization and polymerase chain reaction.

Extragenital Bowens disease (EBD) has rarely been studied for the presence of human papillomaviruses (HPVs). Twenty consecutive patients with EBD were investigated for the presence of HPVs using in situ hybridization with a generic probe that can detect HPV DNA types 6, 11, 16, 18, 30, 31, 33, 35, 45, 51, and 52 and specific probes for HPV DNA types 6/11, 16/18, and 31/33/35. All cases were tested with the polymerase chain reaction (PCR) technique employing the L1 consensus primer pair, MY11 (primer for the positive strand) and MY9 (primer for the negative strand) complementary to genital and dermal HPV types. Seven Caucasian patients, five males and two females, with an average age of 70.4 years, showed positive in situ hybridization (ISH) for HPV DNA. The positivity varied from 5 to 40% of neoplastic cells. Three of seven of the ISH DNA-positive cases showed a positive PCR for DNA HPVs. The role of HPVs in human tumors is not fully understood since oncogenic types of HPVs have been found in normal tissue and the actions of cofactors have been postulated. Bowens disease usually occurs in elderly people in whom the efficiency of the immune systems may be compromised. The association between HPV infection and low efficiency of the immune response may be responsible for HPV-related Bowens disease in elderly people.

Actin-rich desmoplastic malignant melanoma: report of three cases.

We report three cases of desmoplastic malignant melanoma (DMM) rich in smooth muscle actin. They occurred in two men (Cases 1 and 3) and in one woman (Case 2). Cases 1 and 2 were recurrent lesions from common melanomas excised, respectively, 3 and 1 years previously. In Case 3, DMM was associated with lentigo maligna at the time of presentation. Morphologically, DMMs were composed of spindle neoplastic cells organized in haphazardly orientated long fascicles separated by collagen bundles. Perineural invasion was present and mitotic activity was prominent in all cases. The neoplastic spindle cells were intensely positive with S100 protein and smooth muscle actin antisera and negative with HMB45 and Melan-A (Mart-1) antibodies. Double staining for smooth muscle actin and S100 protein revealed no definite coexpression of the two antigens. Follow-up was available for patients 1 and 2 who had local recurrences and are still alive. It is possible that actin rich elements differentiate toward mesenchymal elements, paralleling the phenotypic changes seen in sarcomatoid carcinomas. Therefore, multidirectional differentiation may explain the mesenchymal (sarcomatoid) differentiation of neoplastic melanocytes and may be responsible for the different biologic behavior of DMMs, which is closer to mesenchymal tumors than to conventional melanomas.

Expression of MHC class I and class II antigens in primary breast carcinomas and synchronous nodal metastases

Expression of the major histocompatibility (MHC) class I and class II antigens was studied by immunohistochemistry in a series of 70 primary breast carcinomas and in nodal metastases. In particular, the expression of class I (HLA A-B-C) and class II (DP, DQ and DR) molecules was compared in: a) primary breast cancers devoid of nodal metastases (n = 36) and tumors exhibiting metastatic deposits (n = 34) at the time of surgery, and b) primary breast carcinomas and their corresponding synchronous axillary nodal metastases. Reduced or absent HLA A-B-C antigen expression was seen in approximately 54.3% of primary breast carcinomas, whereas a partial or complete induction of class II products was observed in 18.5% (DQ), 30% (DP) or 48.5% (DR) of the same cases. An almost complete overlap of antigen expression was observed in breast tumors in which no metastases were found by histological examination of axillary nodes and in neoplasms showing histologically-diagnosed synchronous metastases. The reactivity for class I and class II antigens in nodal metastases roughly paralleled that exhibited by corresponding primary tumors. A discordant expression was seen in 11 cases (32%) stained for HLA A-B-C and in 8 (24%), 7 (21%) and 6 (18%) cases assayed for DP, DQ and DR products, respectively. When a discordant expression was detected, either decreased or increased staining patterns were observed in metastases. The finding of overlapping MHC antigenic profiles in the majority of primary breast tumors and nodal metastases casts doubts on the hypothesis that loss of MHC antigens can play an important role in the seeding and growth of metastatic breast carcinoma cells.

Syringoid eccrine carcinoma: a case report.

We report a case of syringoid eccrine carcinoma, a rare syringomatous tumor of the skin, occurring in a 70-year-old woman. Histological and immunohistochemical criteria are given to differentiate this neoplasm from other primary carcinomas of the skin as well as from skin metastases of internal malignancies.

Sclerosing adenosis of the prostate. Report of three cases with electronmicroscopy and immunohistochemical study

Three cases of a rare variant of prostatic adenosis with the features of sclerosing adenosis, an uncommon lesion sometimes confused with prostatic carcinoma, are reported. The lesions consisted of a small, single nodule in prostates otherwise showing typical adenomatous and fibromuscular hyperplasia. The lesions were composed of crowded small glands, small solid nests and individual cells embedded in a cellular stroma. Immunohistochemistry showed that the glands were lined by basal cells positive for high‐weight keratins (EAB‐903 and AE‐3), a finding which confirms the benign nature of the lesion. S‐100 protein and smooth muscle actin were also positive in the same basal cells suggesting myoepithelial differentiation, a character not found in basal cells outside this lesion. This finding was confirmed at ultrastructural level by the finding of numerous thin filaments in the cytoplasm of basal cells. It is important to recognize this lesion in order to avoid confusion with well‐differentiated prostatic carcinoma.

Myxoid metastases of melanoma: report of three cases and review of the literature.

We report three cases of melanoma whose metastases to skin and regional lymph nodes showed myxoid foci, findings absent in their cutaneous primary tumors.

Histoplasma capsulatum var. capsulatum occurring in an HIV‐positive Ghanaian immigrant to Italy

Histoplasmosis, which is highly endemic in the United States, is rare in Europe, usually imported but sometimes autochthonous. In Africa, histoplasmosis capsulati coexists with “African histoplasmosis”, a characteristic skin infection caused by H. capsulatum var. duboisii. Histoplamosis due to H. capsulatum is one of the 12 secondary infections listed in the surveillance definitions of AIDS. We report the case of a 36‐year‐old black man with acquired immunodeficiency syndrome (AIDS) who was living in Italy but originally came from Ghana. Histoplasmosis was disseminated with fever and cutaneous manifestations. The diagnosis was demonstrated morphologically based on the presence of yeast, observed by light microscopy, in skin lesions and by identification of H. capsulatum var. capsulatum DNA by nested PCR from a paraffin sample. No clinical reports of histoplamosis capsulati in Ghana have been published until now. The present case stresses the role of immigration of subjects from outside Europe who have been infected in their native country.

Cutaneous metastasis of chordoma.

A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.

Combined neuroendocrine carcinoma of the skin (Merkel cell tumor) and trichilemmal cyst.

We report a case of neuroendocrine (Merkel cell) carcinoma (NC) of the skin, associated with a trichilemmal cyst, showing pagetoid spread into the trichilemmal epithelium. The association of the two lesions may strengthen the hypothesis that NC originates from pluripotent stem cells of adnexal epithelium.