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Sixty different types of human papillomavirus (HPVs) have been isolated and characterized by molecular cloning in becteria (1). Animal models and pathological studies suggest an estiological role of HPV infection in the development and etiological role of HPV infection in the development of intraepithelial neoplasia and squamous cell carcinoma, particularly in the anogential tract, in the larynx and in edidermodysplasia verruciformis(2,3,4).

Cervicovaginal lavages from 752 pregnant women at term were investigated by polymerase chain reaction to evaluate human papillomavirus (HPV) infection prevalences and were compared with cervicovaginal samples from two series of nonpregnant subjects (504 healthy women attending a family planning service and 560 symptomatic patients attending a vaginitis outpatient service). The odds ratios (ORs) of HPV infection were computed by conditional logistic regression analysis on age-matched sets. In pregnant women, the overall risk of HPV infection was about the same as in nonpregnant healthy subjects (adjusted OR, 0.90; 95% confidence interval [CI], 0.51-1.58) and was 50% less than in patients with symptomatic vaginitis (adjusted OR, 0.48; 95% CI, 0.30-0.76). Moreover, the prevalence of oncogenic HPV types 16 or 18 (or both) was lower in pregnant women (P = .015 and P = .0018 respectively).

Objective: The purpose of this study was to evaluate the frequency and natural history of cervical intraepithelial neoplasia (CIN) during pregnancy in past or current intravenous drug users infected with human immunodeficiency virus type 1 (HIV-1). Study design: We prospectively evaluated 48 pregnant HIV-1 seropositive patients and 38 HIV seronegative controls. All the subjects were current or past intravenous drug users. Follow-up visits were carried out each trimester of pregnancy and 8–12 weeks post-partum with Papanicolau smears, colposcopic examinations and, when necessary, colposcopically directed cervical biopsies. Results: Thirteen of 48 HIV-seropositive women (27.1%) and three of 38 HIV-seronegative controls (7.9%) (P = 0.027 by Fisher exact test) had biopsy-proven CIN at the beginning of pregnancy. High-grade CIN was detected in 10 cases (20.8%) and in two (5.3%) controls (P = 0.058 by Fisher exact test). None of the cervical squamous intraepithelial lesions progressed throughout pregnancy, in both cases and controls. Post-partum cold-knife cervical conization was performed on seven patients with CIN III and examination of the cone biopsy specimens demonstrated persistence of CIN III. Conclusions: HIV-infected intravenous drug users are at high risk of CIN during pregnancy, thus requiring adequate screening programs. Our preliminary data suggest that the progression rate of CIN during gestation is low in this high-risk group.

The authors investigated by PCR 138 infiltrating cervical adenocarcinoma (27 grade 1, 76 grade 2, and 35 grade 3) for the presence of human papillomavirus (HPV) 16 and 18 infection. They included 95 (68.8%) mucinous and 43(31.2%) non-mucinous tumors. The overall prevalence of HPV infection was 84.8%; 28.3% of the cases were positive for HPV 16, 29.7% for HPV 18, and 26.8% for both HPVs. Amplification of HPV 16 and 18 negative cases with consensus primers MY09/MY11 failed to yield any additional tumors with HPV DNA sequences. Patients with HPV infection were younger than the patients who were HPV-negative (P = .001). The type of HPV was unrelated to age. Human papillomavirus infection was found in 95.8% mucinous and in 60.5% non-mucinous tumors (P < .001), with even distribution among grade 1, 2 and 3 adenocarcinoma. Our findings confirm the key role of HPV 16 and 18 in the development of cervical adenocarcinoma, particularly in mucinous histotypes. The absence of HPV infection, the old age of patients and the non-mucinous differentiation may identify a subset of cervical adenocarcinoma with different etiopathogenesis.

Experimental models indicate that activated ras genes and HPV oncogenic sequences may cooperate in inducing a completely transformed phenotype in epithelial cells. We searched for K-ras gene mutations and HPV type-16 and -18 sequences in 67 primary adenocarcinomas of the uterine cervix by analyzing DNAs from formalin-fixed, paraffin-embedded tissue samples. Target sequences were amplified by PCR and analyzed by denaturing gradient gel electrophoresis (DGGE) and sequencing for the detection of K-ras gene mutations and by Southern blotting for the detection of HPV infection. We found 16 mutations in 15 cases; 14 were at codon 12 and 2 at codon 13; 11 were base transitions and 5 were transversions. Mutations were more frequent in mucin-secreting than in non-mucinous tumors. HPV oncogenic sequences were detected in 58 cases with no significant difference between K-ras-mutated and wild-type tumors. HPV oncogenic sequences were also more frequent in mucin-secreting than in non-mucinous tumors. Both molecular events were present simultaneously in 13 out of 58 cases, all of which had histologically grade-2 and grade-3 tumors. Clinico-pathological parameters of the disease and the overall survival, however, were independent of K-ras mutations and of HPV-16 and -18 infection, as shown by univariate and multivariate analysis. In contrast, stage of disease, lymph-node metastases, deep infiltration, clear-cell histology and low grade of differentiation were risk factors for tumor-related death. © 1995 Wiley-Liss, Inc.

Frequency and pattern of expression of eight markers of gastric, intestinal, and pancreatobiliary duct epithelial cells have been investigated by histochemical and immunohistochemical techniques in 85 cases of cervical adenocarcinomas. M1, a mucin antigen, and Cathepsin E (CaE), an aspartic proteinase, markers of normal gastric superficial/foveolar epithelial cells, are expressed in 40 and 55 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or Pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, are found in 24 tumors, 13 of which also express M1 and CaE. CAR-5 and M3SI, markers of intestinal mucin, are expressed in 68 and 12 tumors and DU-PAN-2, marker of normal pancreatobiliary duct cells, is found in 46 tumors. All but two tumors express at least one of the eight markers studied, none express PG I, marker of gastric chief cells. The different histologic subtypes of cervical adenocarcinomas expressed to a variable degree both gastrointestinal and pancreatobiliary markers. Only endocervical type tumors, however, showed the full spectrum of mucosal pyloric type differentiation, including the expression of PGII which is not present in any other histotype. A correlation between expression of gastroenteropancreatic markers and tumor grade is not apparent in our series.

The mean counts of Langerhans' cells were evaluated in cervical biopsies obtained from 30 patients with human immunodeficiency virus (HIV) infection and cervical intraepithelial neoplasia (CIN) and from 30 HIV-seronegative control patients. Each HIV-seronegative control was matched to a seropositive case with respect to grade of CIN, age, and smoking habits. Langerhans' cells were identified by immunohistochemical staining for S-100 protein. In situ hybridization with biotinylated probes was performed to detect human papillomavirus (HPV) DNA 6/11, 16/18, and 31/35/51. The mean counts of S-100 positive cells per 100 basal cells were lower in HIV-seropositive patients than in controls (0.99 +/- 0.08 vs 1.9 +/- 0.2 P = 0.024). These differences occurred independent of any coexisting HPV infection. Positive correlations between S-100 positive cell counts and CD4+ and CD8+ cell counts were found in HIV-infected women. AIDS patients had lower Langerhans' cell counts compared both to patients with AIDS-related complex or asymptomatic HIV infection. Our results suggest that local cervical immunity, as evaluated by Langerhans' cell counts, is impaired in HIV-seropositive women. The severity of impairment seems to correlate with the stage of the HIV disease.

In 100 mucinous tumors of the ovary (37 benign, 24 borderline, and 39 malignant), the authors determined by histochemical and immunohistochemical techniques the frequencies and patterns of expression of a total of nine markers of gastric, intestinal, and pancreatobiliary duct epithelial cells. M1, a mucin antigen, and cathepsin E (CaE), an aspartic proteinase, two markers of normal gastric superficial/foveolar epithelial cells, were expressed in 95 and 92 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, were found in 79 tumors. All of these tumors also expressed M1 or CaE. DU-PAN-2 and the N-terminal epitope of gastrin-releasing peptide, markers of normal pancreatobiliary duct cells, were found in 70 and 49 tumors, respectively, and CAR-5 and M3SI, markers of intestinal mucin, were expressed in 51 and 30 tumors, respectively. All tumors expressed at least two of the nine markers studied; none expressed PG I, a marker of gastric chief cells. The mucopeptic cell marker, PG II, was significantly more common in benign and borderline than in malignant tumors (P less than 0.005), whereas CAR-5 and M3SI, markers of intestinal mucin, were expressed significantly more often in malignant than in benign and borderline tumors (P less than 0.001). By electron microscopic examination, many tumor cells had fine structural features characteristic of gastric superficial/foveolar and pyloric gland cells, intestinal columnar or goblet cells, and endocervical cells. The results indicate that gastroenteropancreatic cell differentiation--and, in particular, gastric type differentiation--is a prominent feature of ovarian mucinous tumors.

The prevalence of lower genital neoplasia and Human Papilloma-virus-related genital lesions were evaluated in a cohort of 75 women with Human Immunodeficiency Virus type 1 (HIV-1) infection at different stages of HIV disease. The overall rate of cervical intraepithelial neoplasia (CIN) in the group studied was 29.3% ( 22 75 ). Eight out of 10 high-grade CIN lesions contained ‘high-risk’ HPV-DNA 16 18 and/or 31/35/51 as demonstrated by ‘in situ’ hybridization with biotinylated probes. Vulvar and/or perianal condylomata were histologically diagnosed in 14 patients (18.7%); nine of these biopsies contained detectable HPV-DNA which was always related to HPV 6 11 . The rate of high-grade CIN in symptomatic HIV-infected patients was 28% ( 7 25 ) as compared to 6% ( 3 50 ) of the other cases (P = 0.022). CD4 lymphocyte counts, white blood cell counts, CD4 + CD8 + cell ratio and percentage of CD4+ lymphocytes were lower in patients with high-grade CIN in comparison to the patients with negative colposcopical and/or cytological examination. After adequate standard treatment (cryotherapy, electrocauterization, cold-knife conization) only one case of CIN 2 recurred during the 2 years of follow-up period. The prevalence of lower genital neoplasia and HPV-related lesions among HIV-infected women is high and seems to correlate with the severity of HIV disease.

M1, a mucin antigen, and cathepsin E, an aspartic proteinase, are both expressed in normal gastric superficial-foveolar epithelial cells. In this study, we determined by immunohistochemical staining the prevalence of these antigens in 316 gastric cancers representative of the main histologic types and stages of the disease. M1 was expressed in 201 cases (64%) and cathepsin E was expressed in 235 cases (75%) of the 313 cases investigated. Both antigens were expressed more commonly in diffuse and mixed cancers than in glandular tumors. M1 was found in 64 of 83 (77%) diffuse cancers and in 48 of 59 (81%) mixed cancers, but in only 74 of 146 (51%) glandular cancers. For cathepsin E, the prevalence was 93% in diffuse cancer, 81% in mixed cancer, and 71% in the 143 glandular cancers examined. Among 25 mucoid tumors, 15 (60%) expressed M1 but only eight (32%) expressed cathepsin E. Overall, 262 (84%) of the tumors expressed at least one of these antigens and of these, 173 (66%) expressed both antigens. No significant difference in the prevalence of M1 or cathepsin E was found between early and advanced cancer or between metastatic and nonmetastatic cancer. The two markers differed in their intracellular localization. In superficial-foveolar cells, M1 immunostaining was concentrated in secretory granules, Golgi complex, and luminal mucous, whereas cathepsin E was found in the endoplasmic reticulum. Moreover, cathepsin E, but not M1, was found in the enterocytes of duodenal villi and, occasionally, in mucopeptic cells. Parallel histochemical and ultrastructural investigations confirmed the occurrence in gastric cancer of foveolar-type cells, manifested by periodic acid-Schiff- and/or alcian blue-reactive mucous granules having a punctate substructure. We conclude that superficial-foveolar cell differentiation is common in gastric cancer and is a major component of this type of tumor. However, pure foveolar cell differentiation is rare. Rather, most gastric cancers consist of cells exhibiting features of foveolar, intestinal, and mucopeptic cell lines.

The combination of ultrasonography (US) and computed tomography (CT) proved useful in recognizing and defining the characteristics of a primitive mucinous cystadenocarcinoma of the retroperitoneum, a rare anatomopathological finding which consistently presents certain macroscopic features that help in the formulation of a diagnosis with imaging techniques.

Seventy-nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40.5 per cent of the cases; the percentage of positive cases was significantly lower in low-grade (G1 and G2) TCCs than in high-grade (G3) tumours (10.6 per cent vs. 84.4 per cent; P < 0.0001). The overall rate of HPV infection was 32.9 per cent; 20.3 per cent of the cases were positive for HPV 16, 3.8 per cent for HPV 18, and 8.9 per cent for both. Consensus primers as well as type-specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low-grade than in high-grade tumours (44.7 per cent vs. 15.6 per cent; P = 0.0061). p53-positive cases were more common among papillary, deeply infiltrating tumours, and HPV-positive cases among papillary, non-infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low-grade and in invasive high-grade tumours is suggested.

Two cases of primary retroperitoneal mucinous cystoadenocarcinoma of the ovarian type are reported. Both tumors occurred in females with bilateral normal ovaries and contained benign, borderline, and malignant mucinous epithelium. Full-thickness infiltration of the cyst wall was not found. In addition to surgery, one patient was given chemotherapy because of spillage from the tumor during intervention. There were no recurrences and no evidence of metastatic disease 19 and 33 months after diagnosis. Histologic findings suggest that the tumors had developed through mutinous metaplasia in preexisting mesothelial cysts.

Objective : Our purpose was to evaluate the proliferative activity of cervical intraepithelial neoplasia lesions in human immunodeficiency virus-seropositive women. Study Design : The proliferative activity of cervical intraepithelial neoplasia lesions was measured by nucleolar organizer regions—associated proteins count. Twenty-two biopsy specimens of cervical intraepithelial neoplasia lesions from patients positive for human immunodeficiency virus were compared with 22 matched biopsy specimens obtained from controls negative for the virus. Results : The mean count of nucleolar organizer regions-associated proteins per cell was 9.5 ± 3.7 (SD) in human immunodeficiency virus-positive patients and 7.6 ± 2.8 in human immunodeficiency virus-negative controls ( p ≤ 0.0001 by Poisson test of heterogeneity of counts). The difference in counts between the two groups, which was confirmed by log-linear analysis, persisted within each severity stratum of cervical intraepithelial neoplasia and was independent of associated human papillomavirus infection. In human immunodeficiency virus-positive patients log-linear analysis showed that high-grade cervical intraepithelial neoplasia, the presence of human papillomavirus infection, and the severity of human immunodeficiency virus disease were independently correlated with increased nucleolar organizer regions—associated protein counts per cell. Conclusion : The results of this study indicate that the proliferative activity of cervical intraepithelial neoplasia lesions of human immunodeficiency virus-positive patients was increased compared with matched lesions from human immunodeficiency virus-negative women. This finding suggests the possibility of an increased oncogenic progression of cervical intraepithelial neoplasia lesions in human immunodeficiency virus-positive patients.

Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.

It has been suggested that women carrying the HLA-DQ3 antigen are at increased risk of developing cervical. squamous cell carcinoma (SCC)1. Since the association between cervical. SCC and human papillomavirus (HPV) types 16 and 18 has been proved by molecular studies2 and in animal. models the tumorigenic effect of HPV may differ according to the immunogenetic background,3 the presence of a given HLA type might help linking environmental. risk factors with individual. susceptibility to cervical. SCC. Subsequent studies however have reported different findings4,5 that could be in part explained by differences in HLA phenotype among populations.

The distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development.

THE ADVENT of sophisticated diagnostic tests has reduced the number of necropsies in patients who die while in hospital, due to the conviction that this procedure is unnecessary for verification of diagnosis [ 1, 21. Many clinicians, however, are rediscovering the benefits of necropsy [3-61. Our experience of the past 10 years has demonstrated that necropsy can reveal unexpected findings, even in apparently simple cases. Of 704 patients treated for gynaecological neoplasms, 54 died in our hospital and necropsy was requested for 29 (54%) (Table 1). Request forms were always filled out by oncology group clinicians, and contained detailed information about the clinical course. A clinician was almost always present at the necropsy. In 9 deaths due to postoperative complications, the clinical diagnosis was confirmed. In a patient with stage IIIC ovarian cancer, who died from a pulmonary embolism, a second primary neoplasm was found in the pancreas. The necropsies in the other 20 cases were done to confirm and evaluate better the spread of disease in patients who died of cachexia. In 2 of these cases necropsy revealed a missed major diagnosis [S]. Case 2 (49 years) underwent first surgery in September 1987 for a stage IV (pleural) serous papillary ovarian carcinoma with residual tumour of 10 cm (the omentum was not removable). On completion of chemotherapy with cisplatin plus cyclophosphamide (with pulmonary disease radiologically negative), a second-look laparotomy demonstrated a good partial response and permitted debulking of the residual omental disease. The patient then received consolidation with the same drugs; at the end of this treatment, in keeping with the protocol [7], a thirdlook laparotomy was done in February 1988 and demonstrated complete response to therapy. The patient did well until July 1988 when intestinal occlusion developed. CT showed abdominal relapse, confirming the suspicions raised at clinical examination. Palliative derivative surgery seemed useless because of diffuse peritoneal carcinomatosis. The patient died 2 months later, and necropsy revealed diffuse fibrous adhesions conglobating the large and small intestines; however, no tumour was found in the abdominal cavity. Only a microscopic residual tumour was present in the pleural cavity. Thus modern technology has not eliminated the need for postmortem verification: diagnostic imaging may have serious difficulties in the differential diagnosis between neoplasia and some therapy complications [8]. Necropsy provides valuable medical audit and can uncover missed diagnoses which could be helpful for future practice. When possible necropsy should be performed in all cases, and an effort should be made to overcome the natural resistance of relatives.

Two pregnancies of a family at risk for Sanfilippo disease type B were monitored in the first trimester. In one case an affected fetus was diagnosed on chorionic villi by the assay of N-acetyl-alpha-D-glucosaminidase and confirmed on cultured fibroblasts from the aborted fetus. Pathological findings are also reported and compared with changes observed later in life. The disease was excluded in the second pregnancy.

The ultrastructure of immunohistochemically identified PP cells has been investigated by applying the serial semithin/thin section technique to the human pancreas, with special reference to the posterior part of the head, reputed to originate from the ventral primordium. PP cells of this area differ from those already identified in the rest of the pancreas and correspond to a cell, not yet described in the human pancreas, characterized by larger granules of very variable shape and structure. Such granules resemble those of so-called "F cells", i.e. the PP cells of dog uncinate process and cat duodenal lobe, also coming from the ventral primordium. Thus, human "ventral lobe" PP cells have peculiar potentialities which are expressed in distinctive structural patterns of presently unknown functional meaning.

Summary Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucos al signet-ring cell type. in general, an increased tendency to foveolar cell, differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.

Endocrine-paracrine cells are specialized cells scattered in the epithelium lining the gastric glands, intestinal crypts, and villi. They are characterized by secretory granules, which, as a rule, are concentrated in the basal part of the cytoplasm, while the Golgi complex is supranuclear. In the pyloric and intestinal mucosa, most of such cells reach the lumen in a narrow, specialized area showing tufts of microvilli and a centriole; this area probably acts as a receptor surface facing the luminal contents (Solcia et al. 1967). Such a pattern suggests some functional polarity of the cell (Figs. 1, 2). In the fundic mucosa endocrine-paracrine cells lack luminal contacts and show less evident polarity (Solcia et al. 1975).

BD-5 monoclonal antibody reacted with tumour cells in 262 of 316 cases of gastric cancers, including 121 of 134 early, 141 of 182 advanced tumours (p less than 0.01), and 113 of 146 glandular, 72 of 83 diffuse, 22 of 25 mucoid, and 55 of 59 mixed tumours. No difference in reactivity was observed between metastatic and non-metastatic advanced tumours. Immunocytochemical techniques applied to light and electron microscopical specimens of colorectal mucosa and gastric cancer showed that BD-5 immunoreactive material occurred in the Golgi complex, in small clear, to dense cored, cytoplasmic vesicles, and in the glycocalix of the luminal and lateral membranes of normal and neoplastic cells in the glands, as well as in the peripheral membrane of dispersed neoplastic cells. Mucin granules stored in the cytoplasm of goblet cells were unreactive or poorly reactive. Ultrastructural features consistent with colorectal type differentiation were observed in many reactive tumours. Unreactive tumours showing ultrastructural patterns consistent with intestinal differentiation, especially of small bowel type, were also observed. Signs of intestinal differentiation, including BD-5 immunoreactivity, often occur in gastric cancer, irrespective of histological type and stage of disease.

A series of 15 Merkel cell tumours of skin is reported. They occur dominantly on the head and neck and on the extremities of elderly women, frequently presenting as a reddish nodule. Three cases were associated with squamous carcinoma at the same site, an association deserving further study. There are two main patterns: the commoner one takes the form of a trabecular carcinoma in the dermis mimicking metastatic carcinoma, including oat-cell carcinoma and neuroblastoma: a dissociated-cell form mimicks malignant lymphymphoma. The triad of vesicular nuclei with very small nucleoli, abundant mitotic activity and apoptosis is so characteristic as to be virtually pathognomonic in conjunction with structural features. Argyrophilia is common, but Bourn fixation is necessary to demonstrate it regularly. Small round secretory granules (89 ± 18 nm) with narrow haloes, and an abundance of intermediate size filaments are among the ultrastructural hallmarks. There is a close similarity between better differentiated tumour cells and normal Merkel cells. The neural crest origin of MC is in doubt both on the basis of studies of the development and regeneration of MC and from the study of Merkel cell tumours.

Objective: To evaluate the risk of perinatal human papillomavirus (HPV) transmission from mothers with latent infections to the oropharyngeal mucosae of their infants. Methods: Seven hundred eleven mother-newborn pairs were tested. Polymerase chain reaction was done with MY09/MY11 consensus primers to identify HPV DNA in maternal cervicovaginal lavages and newborn nasopharyngeal aspirates. Positive cases were further amplified with type-specific primers for HPVs 6, 11, 16, 18, and 33. All infants born to HPV-positive mothers were observed to 18 months for appearance of HPV in oropharyngeal mucosae. Results: Human papillomavirus DNA was detected in 11 neonates born vaginally to HPV-positive women, a vertical transmission rate was 30% (95% confidence interval [CI] 15.9, 47). Nasopharyngeal aspirates were HPV-negative in all 11 cases in which rupture of membranes occurred less than 2 hours before delivery. When rupture preceeded delivery by 2–4 hours, and when it occurred after more than 4 hours, the respective rates for HPV positivity were seven of 21 and four of five ( χ 2 for trend = 10.7, P = .001). At follow-up, virus was cleared from the oropharyngeal samples as early as the 5th week. Conclusion: Pregnant women with latent HPV infections have low potential of transmitting the virus to the oropharyngeal mucosae of their infants. The time between rupture of the amnion and delivery seems to be a critical factor in predicting transmission. Human papillomavirus–positive infants should be considered contaminated rather than infected since virus is cleared over several months after birth.