Feasibility of vaginal mesh for anterior vaginal wall prolapse in an ambulatory setting: A retrospective case series.

INTRODUCTION: Vaginal mesh has been proven to be an effective aid in the treatment of cystocele. Could an ambulatory approach be feasible for the Uphold Lite®-mesh? HYPOTHESIS: We investigate the feasibility of an ambulatory approach of Uphold Lite® insertion in a well-selected population. Risk factors for a non-successful ambulatory approach are identified. METHODOLOGY: We conducted a retrospective case series of 236 women who underwent Uphold Lite® vaginal mesh insertion for the treatment of pelvic organ prolapse at our center. Indications for surgery were symptomatic anterior and/or apical prolapse, stages POPQ≥2. We compared women having an ambulatory approach, to those having a one day hospitalization planned but needed to stay. Comparisons between percentages were calculated using the chi-square or Fisher's exact test, depending on the number of women in each group. The mean comparisons were performed using the Student t-test, and the median test comparisons by the Kruskal-Wallis test. A difference was considered significant if p<0.05. RESULTS: The most common reason for staying (85.7% of all ambulatory failures) after Uphold® surgery is the presence of an elevated post void residual. This complication was more found in the following: surgery in the afternoon, use of high-dose morphinics in general anesthesia, and in women with a higher parity. CONCLUSIONS: Our study shows that Uphold® surgery in a one-day setting is feasible and safe. Women desiring this approach should be counselled on the 42.6% risk of one-day failure though, mostly due to non-validation of a post void residual. General anesthesia with high-dose morphinics, a higher parity, and surgery in the afternoon are risk factors for failure of an ambulatory protocol.

Hepatocellular carcinoma with distant double bile duct tumoral thrombus: a case report.

The authors report a case of a 3 cm hepatocellular carcinoma at the junction of segments VI and VII with double bile duct tumoral thrombi (Types I and III). The type I thrombus was suspected during the pre-operative workup, but the type III bile duct tumoral thrombus (BDTT) was an intra-operative additional finding on cholangiography. The patient underwent a bisegmental posterolateral resection to remove the primary tumour and the first tumoral thrombus located in the posterolateral intrahepatic duct. A choledocotomy was also performed to remove, by balloon catheter, the floating thrombus located in the common bile duct just over the papilla. The authors discuss their diagnostic and therapeutic approach and review the literature.

High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma.

PURPOSE: To determine the toxicity and the therapeutic efficacy of the combination of the recombinant tumor necrosis factor alpha (rTNF alpha), recombinant interferon gamma (rIFN-gamma), and melphalan, we designed a protocol using isolation limb perfusion (ILP) with hyperthermia for in-transit metastases of melanoma and recurrent sarcoma. The triple combination was chosen because of the reported synergistic antitumor effect of rTNF alpha with IFN-gamma and of rTNF alpha with alkylating agents. PATIENTS AND METHODS: Twenty-three patients received a total of 25 ILPs with the triple combination. There were 19 females and four males with either multiple progressive in-transit melanoma metastases of the extremities (stage IIIa or IIIab; 19 patients) or recurrent soft tissue sarcoma (five). The rTNF alpha was injected as a bolus in the arterial line, and total dose ranged between 2 and 4 mg, under hyperthermic conditions (40 degrees C to 40.5 degrees C) for 90 minutes. The rIFN-gamma was given subcutaneously (SC) on days -2 and -1 and in the perfusate, with rTNF alpha at the dose of 0.2 mg. Melphalan (Alkeran; Burroughs Wellcome Co, London, England) was administered in the perfusate at 40 micrograms/mL. RESULTS: Toxicity observed during three ILPs in a pilot study with rTNF alpha included only two severe toxicities: one severe hypotension with tachycardia and transient oliguria and one moderate hypotension for 4 hours followed by severe kidney failure with complete recovery on day 29. In all 18 ILPs performed in the triple combination protocol, the patients received continuous infusion dopamine at 3 micrograms/kg/min from the start of ILP and for 72 hours and showed only mild hypotension and transient chills and temperature. Regional toxicity attributable to rTNF alpha was minimal. There have been 11 cases with hematologic toxicity consisting of neutropenia (one grade 4 and one grade 3) and neutropenia with thrombocytopenia (one grade 4 and three grade 2). Twelve patients had been previously treated with melphalan in ILP (11) or with cisplatin (one). The 23 patients are assessable: there have been 21 complete responses (CRs; range, 4 to 29 months; 89%), two partial responses (PRs; range, 2 to 3 months), and no failures. Overall disease-free survival and survival have been 70% and 76%, respectively, at 12 months. In all cases, softening of the nodules was obvious within 3 days after ILP and time to definite response ranged between day 5 and 30. CONCLUSION: This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration. Tumor responses can be evidenced in melanoma and sarcoma. Furthermore, combination of rTNF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy with melphalan alone.

Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients.

PURPOSE: A prospective study was performed to assess plasma measurement of tumor necrosis factor (TNF), lymphotoxin alpha (LTalpha), and their soluble receptors (p55 and p75) for prognostic risk assignment in patients with malignant lymphomas. PATIENTS AND METHODS: One hundred forty-two patients, 124 with non-Hodgkin's lymphoma (NHL) and 18 with Hodgkin's disease (HD), were analyzed. Plasma samples were tested by enzyme-linked immunoabsorbent assay (ELISA). RESULTS: Elevated plasma levels of TNF, p55,and p75 were associated with an Eastern Cooperative Oncology Group (ECOG) status > or = 2, Ann Arbor stage III/IV, elevated serum lactate dehydrogenase (LDH) and beta2-microglobulin levels, > or = two involved extranodal sites, B symptoms, anemia, and low serum albumin level. Elevated levels of p55 and p75 were associated with older age and higher values of C-reactive protein. TNF, p55, and p75, but not LTalpha, plasma levels higher than median predicted shorter freedom from progression (FFP) survival and overall survival. Three distinct risk groups for patient outcome were identified: patients with low risk (TNF, p55, and p75 below median values), intermediate risk (one or two parameters higher than median), and high risk (all three parameters higher than median). At a median follow-up duration of 25 months, the actuarial 2-year FFP survival rates were 79%, 60%, and 37%, respectively (P < .0001), and overall survival rates were 91%, 82%, and 51% (P < .0001). The addition of the TNF ligand-receptor-based model to the International Prognostic Index (IPI) yielded a significant improvement of the predictive value of IPI. CONCLUSION: TNF and its soluble receptors' plasma measurements represent valuable prognostic markers in lymphoma patients.

Proliferation of MIELIKI a novel t(7;9) early pre-B acute lymphoblastic leukemia cell line is inhibited concomitantly by IL-4 and IL-7.

The present study describes a novel cell line, MIELIKI, established from bone marrow of a pediatric patient with B lineage acute lymphoblastic leukemia (ALL) at diagnosis. The MIELIKI cell line displays an early pre-B cell phenotype (CD10+, CD19+, CD20+, CD34-, Cmu-, sIg-) with rearrangements on both Ig heavy chain and k light chain alleles, and carries an unfrequent t(7;9) chromosomal translocation identical to the freshly isolated leukemic blasts. The proliferation of MIELIKI cells was abrogated by IL-4 and by IL-7, as measured by DNA replication and viable cell recovery. The effects of IL-4 and IL-7 were mediated, respectively, through the CDw124 and CDw127 IL-4 and IL-7 receptor components. Growth inhibition by IL-4 was not mediated by soluble factors released by MIELIKI cells in response to IL-4, suggesting the existence of an intrinsic negative signaling pathway. Finally, neither IL-4 nor IL-7 were found to induce maturation of MIELIKI into cells expressing cytoplasmic or surface membrane mu chain. The present cell line should constitute a useful model of t(7;9) early pre-B ALL and allow investigation of the relationship between IL-4 and IL-7 negative signaling in leukemic B cell ontogeny.

Characterization of germinal center dendritic cells in follicular lymphoma.

A subset of dendritic cells called germinal center dendritic cells (GCDC) has recently been described inside germinal center from reactive lymphoid organs. We investigated this newly recognized population in follicular lymphoma (FL), which is considered to be the pathologic counterpart of germinal center B cells. Immunohistochemistry analysis with a panel of antibodies demonstrated the presence of a cell population with the peculiar GCDC phenotype in FL biopsies and a similar localization of these cells inside tumoral and reactive follicles. Therefore, we analyzed the relationships between GCDC and the other cell subsets of the tumor follicles. Some of CD4+ and CD8+ T lymphocytes present inside the follicle were found to be in close association with GCDC, suggesting a potential implication of GCDC in their activation. In addition, the distribution of GCDC inside FL and reactive follicles did not appear disrupted, in contrast to follicular dendritic cells, the other follicle dendritic cell type. Finally, we demonstrated that GCDC could be detected from FL lymph node cell suspension by flow cytometry. Taken together, these results indicate that FL development is not associated with a disappearance of GCDC or with a lack of physical interactions between GCDC and T cells inside the follicles. In addition, the fact that GCDC can be observed in FL samples by flow cytometry should allow their purification to further study their putative role in FL development and maintenance.

Rapid induction of anti-idiotypic responses to unmodified monoclonal antibodies from syngeneic mice following primary immunization.

A single foot-pad immunization in adjuvant of BALB/c mice with non-modified BALB/c monoclonal antibodies (HyHEL 5, 9 and 10) specific for hen egg lysozyme permitted isolation of anti-idiotypic monoclonal antibodies 10 days later. An evaluation of different screening tests revealed that antibodies were detected more easily by isotype-specific or direct binding assays than by cross-linking ELISA procedures. These results were confirmed by a direct cell-binding assay on B cells transgenic for one of the immunizing antibodies. The use of these cells also permitted an evaluation of the ability of these antibodies to inhibit antigen binding under conditions in which the target antibody, in its cell-surface configuration, is minimally modified by potential artifacts induced by purification or fixation to a solid support. This study demonstrates that anti-idiotypic responses to anti-protein antibodies may be rapidly generated in syngeneic animals.

Dopaminergic lateral efferent innervation of the guinea-pig cochlea: immunoelectron microscopy of catecholamine-synthesizing enzymes and effect of 6-hydroxydopamine.

We have used an immunocytochemical approach to gain further data supporting a possible neurotransmitter or neuromodulator function for dopamine at the level of efferent (olivocochlear) innervations of the guinea-pig cochlea. Immunofluorescence screening was first done on cochleas two or seven days after infusion with the neurotoxin 6-hydroxydopamine. Two days after neurotoxin perfusion, the intensity of the tyrosine hydroxylase-like immunoreactivity was decreased in the inner and tunnel spiral bundles of the organ of Corti (and in known noradrenergic sympathetic fibers outside this organ), with respect to the control contralateral cochleas. In cochleas screened seven days after 6-hydroxydopamine infusion, no tyrosine hydroxylase-like immunoreactivity could be found in the organ of Corti. Only occasional faint fluorescence could be detected in sympathetic fibers. In another set of experiments, a pre-embedding immunoperoxidase technique was used to localize tyrosine hydroxylase and aromatic amino acid decarboxylase, another catecholamine-synthesizing enzyme, at the ultrastructural level. With both types of antibody, the same kind of results were observed. Immunoreactivities were only seen in vesiculated fibers within the inner and tunnel spiral bundles, thus are likely in lateral efferent varicosities. These immunostained fibers accounted for approximately half of the efferent profiles in the inner spiral bundle. Within this bundle, the immunoreactive fibers established axodendritic synapses with the radial afferent processes of type I neurons which contacted the inner hair cells. In no case was immunoreactivity to either enzyme observed in the outer hair cell region, at the level of medial efferent terminals. The synaptic localization of tyrosine hydroxylase- and aromatic amino acid decarboxylase-like immunoreactivities in the lateral efferent varicosities of the inner spiral bundle, as well as the effect of 6-hydroxydopamine on the tyrosine hydroxylase-like immunoreactivity in this same bundle, further support the hypothesis that a catecholamine could act as a lateral efferent neurotransmitter or neuromodulator. Based on previous data reporting a lack of dopamine-beta-hydroxylase-like immunoreactivity within the organ of Corti, and the effectiveness of a D2 agonist on the cochlear compound action potential of the auditory nerve, this catecholamine could well be dopamine.

Heterogeneity of the inhibitory effects of IL-4 in two novel B lineage acute lymphoblastic leukemia cell lines.

The present study describes two novel cell lines, DUNATIS and SILVANUS, established from B lineage acute lymphoblastic leukemia patients. Respectively, DUNATIS and SILVANUS display an early pre-B cell and a pre-B cell phenotype. Spontaneous DNA replication of both cell lines was strongly inhibited by IL-4. This effect was directly mediated by IL-4 and exerted through the CD124 IL-4 receptor chain. Notably, IL-4 was associated with rapid cell death and reduction of cellularity in DUNATIS, whereas these parameters were considerably less pronounced and only observed after longer-term exposure of the SILVANUS cells to IL-4. In addition to these differences, although both cell lines expressed FES oncoprotein, a 100 kDa protein associated with FES was strikingly found to be tyrosine-phosphorylated in response to IL-4 exclusively in DUNATIS cells. These data demonstrate that IL-4 displays heterogenous effects on leukemic B cell precursors responsive to inhibition of DNA synthesis via IL-4 mediated engagement of the CD124 receptor chain. The present findings may be of use for appreciation of the effects of IL-4 in B lineage ALL, and the novel cell lines could represent a model for further identification of target molecules in IL-4 signalling.

Correlation between complete response to anthracycline-based chemotherapy and topoisomerase II-alpha gene amplification and protein overexpression in locally advanced/metastatic breast cancer.

UNLABELLED: Anthracycline-based regimens are among the most active but also with greater risk of both acute and long-term side effects, namely cardiotoxicity. Predictive markers of response to anthracyclines are therefore essential. Topoisomerase-IIalpha (topo-II) is the target of anthracyclines and preliminary data suggest its promising role as a predictive marker of sensitivity to these drugs. After screening a population of about 350 patients with locally advanced or metastatic breast cancer, two subgroups were selected for the present analysis: a study group (31 patients), composed of 14 complete responders (CR-a) and 17 true non-responders (PD-a) to anthracycline-based CT, and a control group (28 patients), composed of 7 CR (CR-t) and 21 true non-responders (PD-t) to taxane-based CT. True non-responders were defined as progressive disease (PD) within the first three cycles of CT. Archival tumor samples of these patients were collected, biological markers evaluated and their status correlated with response to therapy. HER-2 and topo-II gene status were evaluated by FISH (Vysis multi-color probe-positivity cut-off: >/=2 ratio for HER-2 and >/=1.5 for topo-II), topo-II protein was evaluated by IHC (positivity cut-off >10%). All cases in which HER-2 gene was non-amplified did not show topo-II gene aberrations. No association was found between HER-2 gene amplification and response to anthracyclines (5/14 (36%) CR and 5/17 (29%) PD to anthracycline-based CT were HER-2+). The topo-II gene was amplified in 3/14 (21%) CR but only in 1/17 (6%) PD to anthracyclines. Amplification of the topo-II gene was seen in 1/7 (14%) CR and in 3/21 (14%) PD to a taxane-based CT. Topo-II protein was overexpressed in 6/11 (55%) CR and in 2/17 (12%) PD to anthracyclines, while in the control group, overexpression was seen in 5/7 (71%) CR and 8/20 (40%) PD. IN CONCLUSION: i) HER-2 gene amplification did not seem to be correlated with response to anthracyclines. ii) Both topo-II gene amplification and protein overexpression seem to correlate with response to anthracyclines, although other factors, such as p53 and cell proliferation, are most likely to be involved. iii) The role of combined evaluation of several relevant markers and of potential 'molecular signatures' are currently being evaluated in prospective randomized clinical trials.

Antisense oligonucleotides to the GluR2 AMPA receptor subunit modify excitatory synaptic transmission in vivo.

In the brain, fast wxcitatory synaptic transmission is mostly mediated by the alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) subtype of the glutamate receptors. Molecular cloning has revealed that four subunits, GluR1, GluR2, GluR3, and GluR4 form heteromeric receptors with high affinity for AMPA. Because antagonists and agonists do not discriminate between individual AMPA receptor subunits, we decided to use antisense oligonucleotides to block the expression of the GluR2 subunit within the receptor complex in adult animals. In the present study, we exploited several advantages afforded by the guinea pig cochlea to determine whether an antisense oligonucleotide directed to the mRNA of the GluR2 subunit could modify primary auditory neurotransmission. While a random probe with the same base composition had no effect, a GluR2 antisense oligonucleotide, continuously delivered into the cochlea, transiently reduced the compound action potential and diminished spontaneous activity of single auditory nerve fibers. Although antisense oligonucleotides penetrated a variety of cells, their effect could be physiologically localized to a single site of GluR2 antisense probe action, the primary auditory neuron. Subunit specificity of this effect was confirmed by a significant reduction in GluR2/3, but not GluR4 immunoreactivity in primary auditory neurons. Besides being the first demonstration that transient knockout of GluR2 subunit in adult animal modifies excitatory synaptic transmission in vivo, these results support the use of the antisense strategy as a powerful tool for blocking expression of any gene in the cochlea.

Molecular cloning and expression of alpha parvalbumin in the guinea pig cochlea.

We have cloned and sequenced an alpha parvalbumin cDNA from the guinea pig cochlea. The deduced amino acid sequence shows greater identity with the rabbit sequence (86.3%) than with other mammalian sequences (< 82%). Using in situ hybridization and immunohistochemistry, alpha parvalbumin mRNA and protein were found in primary auditory neurons and inner hair cells, in agreement with RT-PCR data showing alpha parvalbumin mRNA expression in the spiral ganglion and the organ or Corti.

Protein kinase C may be involved in synaptic repair of auditory neuron dendrites after AMPA injury in the cochlea.

A suitable model of sudden deafness occurring after acoustic trauma or ischemia, is obtained in guinea pigs by an acute intracochlear perfusion of 200 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate analog. By overloading the AMPA/kainate receptors, located post-synaptically to inner hair cells (IHCs), it induces a massive swelling of primary auditory neuron dendrites, which disconnects the IHCs. This synaptic uncoupling and the resulting hearing loss are followed by a progressive regrowth of dendrites, which make new synapses with IHCs, leading to a functional recovery of auditory responses that is completed after 5 days. Knowing the role of protein kinase C in neuroplastic events, we studied the expression of its isoforms alpha,beta(I,II) and gamma, respectively pre- and post-synaptic, in auditory neurons at various times after AMPA administration. In untreated cochleas, we observed an expression of PKC alpha,beta(I,II) and gamma in cell bodies of primary auditory neurons. After the intracochlear administration of AMPA, both isozymes were transiently overexpressed, with a peak at 3-6 h, followed by a decrease after about 24 h. At this point in time immuno-electron microscopy revealed some regrowing dendrites immunoreactive for PKCgamma. Five days after AMPA, when the auditory responses were restored, PKCgamma levels were still elevated in ganglion cell bodies.

Modulation of costimulatory molecules on follicular lymphoma cells by TNF and CD40.

TNF has recently been implicated in the formation of germinal center cells in lymphoid organs. Follicular lymphoma (FL) is thought to represent the pathological counterpart of germinal center B-cell. High levels of TNF and its soluble receptors were found in the plasma of FL patients whereas the transcripts of these molecules were previously found to be present in FL patients lymph nodes. We therefore studied here the effects of TNF on the expression of costimulatory molecules implicated in the cytotoxic T cell response on purified FL cells. In contrast to results described with B-type chronic lymphocytic leukemia, also characterized by high levels of circulating TNF, none of the tested samples showed a regulation of CD80, CD86, CD27 and CD70 in response to TNF. To confirm that the lack of regulation of these molecules was not due to the FL cells inability to modulate their expression, we therefore analyzed costimulatory molecules expression after CD40 pathway stimulation. After culture with human CD40L-transfected L-cells, an up-regulation of CD80, CD86 and CD70 expression was observed, while TNF addition in this model did not influence these changes. In this context, the CD27 molecule was down-regulated except in a single case, where its expression was increased. Taken together, this data demonstrates that in vitro expression of costimulatory molecules such as CD80, CD86, CD27 and CD70, which are implicated in the anti-tumoral response, can be regulated by CD40 ligand but not by TNF.

Correlation between gender and cytomorphonuclear characteristics in human melanomas and in vitro evidence of sex steroid-induced modifications in the morphonuclear characteristics of three human melanoma cell lines.

The influence of gonadal steroids on human melanoma still remains a controversial issue. The aim of our study was to investigate whether sex steroids may influence the biological characteristics of human melanoma. Such biological characteristics were monitored at the morphological level by means of computer-assisted microscope analysis of Feulgen-stained nuclei, which provides 28 quantitative variables describing the nucleus morphometry (size, anisonucleosis level) and chromatin pattern. This methodology was used to characterize the morphonuclear features in a series of 69 human melanomas (from formalin-fixed paraffin embedded tissues) including 28 male, 17 premenopausal and 24 postmenopausal female patients, and to investigate the effect of two sex steroids (5-alpha-dihydrotestosterone [DHT] and 17-beta-oestradiol [E2]) on three human melanoma in vitro models--the HT-144, SK-MEL-28 and C32 cell lines. The results show that the morphonuclear characteristics of melanoma originating from male and female patients are very distinct (P < 0.01). This difference is still more marked (P < 0.0005) when only premenopausal female patients are compared with male patients. The in vitro data show that both DHT and E2 are able to modify markedly (P < 0.001 to P < 0.0001) the nucleus morphometry and chromatin pattern of the three cell lines. Although the mechanism and the physiological outcome are still unknown, the present work shows that there is in vivo and in vitro evidence that the biological behaviour of human melanoma is influenced by sex steroids.

Glutamine synthetase and glutamate metabolism in the guinea pig cochlea.

Glutamate is thought to act as a neurotransmitter of the sensory hair cells of the organ of Corti. Glutamine synthetase could be involved in a type of glutamate-glutamine cycle in the cochlea which could clear glutamate off the synaptic cleft and replenish the hair cell glutamate neurotransmitter store. Using both light and electron microscopic immunocytochemistry to localize this enzyme in the guinea pig cochlea, we have observed immunoreactive satellite glial cells surrounding parvalbumin-immunoreactive primary auditory neurons in the spiral ganglion. Glutamine synthetase was also detected in Schwann cells of the osseous spiral lamina which form the myelin sheath of nerve fibers. On the contrary, no immunoreactivity could be observed in the cochlear nerve and in the organ of Corti, although this organ contains structures able to take up glutamate. Although they confirm earlier works involving glutamine synthetase in the conversion of L-[3H]glutamate taken up by glial cells, our results suggest that the cochlear glutamate-glutamine cycle is not primarily involved in the recycling and replenishment of hair cell neurotransmitter glutamate. Alternatively, it is proposed that glutamine synthetase functions to limit the perilymphatic glutamate concentrations.

Immunocytochemical detection of choline acetyltransferase in the human organ of Corti.

In the mammalian cochlea acetylcholine has been considered a major neurotransmitter of the lateral and medial efferent fibers. The aims of the present study were to investigate the expression of ChAT in the human cochlea and to develop a new method for immunohistochemical investigations in the human cochlea both at the light and electronmicroscopic level. We thus examined the ChAT-like immunoreactivity in the human inner ear using light and electron microscopy with a pre-embedding technique. Our present results agree with the previously published data acquired in rodent species. The ChAT-like immunostaining could be found in the inner spiral fibers, the inner spiral bundle, tunnel crossing fibers and at the base of the outer hair cells. No staining was noted in the negative controls experiments, while rat cochleas used as positive controls showed the usual ChAT-like immunostaining as described above. The main difference between human and rat cochleas was that the efferent nerve supply seems to be less pronounced in the human cochleas.

Cutaneous cysts: a plea for systematic analysis.

So-called cutaneous cysts are extremely frequent tumours that could need surgical attention. Most of the time, due to their quite pathognomonic clinical presentation and indolent course, they are simply enucleated. Often, the clinical diagnosis is easily confirmed at surgery by the typical appearance of a cystic formation filled with a creamy fluid. It is frequent for such "typical" lesions to escape histological investigation following removal. However, some mimicking lesions could also be found as "cutaneous cysts" and have quite different prognoses. This paper present five patients with such lesions, three basal cell carcinomas, one benign proliferating trichilemmal cyst and a malignant proliferating trichilemmal cyst. None of the lesions was clinically distinguishable from a classical epidermis cyst.

Apocrine adenocarcinoma of the nipple: a case report.

Apocrine adenocarcinoma of the skin is a rare and, most of the time, clinically misdiagnosed malignant adnexal tumour. A 66-year-old female patient presented with an asymptomatic swelling of the left nipple that on pathological evaluation was confirmed as an apocrine adenocarcinoma. Surgery is to be considered as the mean treatment for such a lesion and the diagnosis is always difficult to establish. To our best knowledge, this is only the second reported apocrine adenocarcinoma arising from a nipple and the first presenting with Paget's phenomenon.