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The aim of the study was to assess incidence rate, hormonal activity, and local invasiveness and evaluate outcomes of so-diagnosed atypical pituitary adenomas that underwent endoscopic endonasal surgery at the Division of Neurosurgery of Universita degli Studi di Napoli Federico II. According to the 2004 WHO classification, atypical pituitary adenomas are defined by an invasive growth, Ki-67/MIB-1 proliferative index greater than 3 %, high p53 immunoreactivity, and increased mitotic activity. A retrospective analysis of a series of 434 pituitary adenomas that underwent endoscopic endonasal surgery at our department between March 2007 and February 2013 was performed. Fifty adenomas (11.5 %) met the criteria of diagnosis of atypical lesions; 10 (21.6 %) of the 50 patients were recurrent tumors with a previous transsphenoidal surgery. Forty-one (82 %) were macroadenomas, and 21/50 (42 %) showed a clear invasion of the cavernous sinus. Histotype of atypical adenomas figured out to be nonfunctioning in 23 cases (46 %), PRL secreting in 10 cases (20 %), ACTH secreting and GH secreting each apart in 8 patients (16 %), and in a single case a GH/PRL secreting adenoma (2 %). The Ki-67 labeling index ranged from 3.5 to 22.5 % (mean 5.6 %). Tumor recurrence was observed in six cases (12 %) after a mean time of 18 months (range 9-24 months). Mean follow-up was 36.5 months (range 2-80 months). Atypical pituitary adenomas account for ca. 10 % of all pituitary adenomas; these lesions have peculiar features. It should be considered that a strong immunopositivity of p53 and higher Ki-67 LI could predict an increased risk of tumor recurrence, but more studies and larger series are expected to confirm and enlarge the diagnostic and therapeutic management process of these lesions.

In this paper we report the 1st case of a congenital intracranial mesenchymal chondrosarcoma in a 2-month-old infant, apparently present at birth. A magnetic resonance image showed a large left parietal solid mass, while microscopy revealed a mixture of undifferentiated small cells and mature hyaline cartilage islands, positive for vimentin, S-100, and CD99. A surgical excision was performed but the patient died after a few weeks as a result of a rapid relapse of the tumor. We also review the pediatric cases (in patients less than 20 years old) of extraskeletal (intracranial) mesenchymal chondrosarcomas of the literature, with a focus on the most recent cytogenetic and immunohistochemical studies.

Object The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors. Methods Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor–β [TGFβ], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFβ expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFβ, PDGF, and tenascin in more aggressive cavernomas. Conclusions The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.

Background and Objectives B-cell MALT lymphoma is a well-recognized entity and its characterization as low-grade (LG) and high-grade (HG) lymphoma has been widely accepted. In the present study we reviewed a series of 95 surgical specimens of primary gastric MALT lymphoma selected between 1979 and 1998. Immunohistochemical expression of p53, bcl-2, and Ki67 and Helicobacter pylori (Hp) infection was evaluated, along with a correlation with clinical outcome. Methods A morphologic and immunohistochemical analysis, including p53, bcl-2, and Ki67 expression, was carried out in all cases. A complete follow-up was obtained in 49 patients and in these cases a survival analysis was performed. Results bcl-2 protein was highly expressed in 25 of 25 assessed LG tumors and in 20 of 24 assessed HG tumors. p53 protein was expressed in 13 of 25 assessed LG tumors and in 21 of 24 assessed HG tumors. High proliferation rate as expressed by Ki67 was detected in 15 of 25 assessed LG tumors and in 23 of 24 assessed HG tumors. Hp infection was detected in 11 of 16 assessed LG tumors and 2 of 10 assessed HG tumors. Median survival rates were 72 months for LG tumors and 24 months for HG tumors. Conclusions A significant inverse relationship between Hp infection and histological grade was found. High p53 expression and high-proliferation rate correlated with HG tumors. However, a correlation between p53, bcl-2, and Ki67 expression with clinical outcome was not found. J. Surg. Oncol. 2003;83:106–111. © 2003 Wiley-Liss, Inc.

We have established a cell line (TB) from a cerebrospinal fluid (CSF) specimen of a patient with a primary leptomeningeal melanomatosis. TB cell line was immunoreactive with the antibodies for low molecular weight neurofilament protein, vimentin, neuron-specific enolase, chromogranin, synaptophysin and HMB-45 (an antibody sensitive and specific for melanoma). When TB cells were transplanted into nude mice, the same immunohistochemical pattern present in cultured cells was found but surprisingly, a positive staining for desmin was observed. Significant amounts of serotonin and its metabolite were detectable. Retinoic acid but not nerve growth factor was able to induce differentiation towards a neuronal phenotype. In summary, TB cells represent primitive neuroectodermal cells having the potential for neuronal, myoblastic and possibly melanoblastic differentiation.

• Intracranial Mycobacterium avium complex (MAC) infection in immune-competent hosts is exceptional.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with increased risk of embryonal tumors, such as Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma. We report on a patient with BWS that developed a giant fibroadenoma of the breast that was surgically removed. The tumor relapsed 8 months after the surgery and the patient underwent partial mastectomy. Although the patient presented several clinical features of BWS, a molecular diagnosis was not achieved despite extensive molecular investigations on both blood and tumor tissue. A SNP array revealed a de novo 7p22.1 loss in both blood and breast tumor involving the mismatch repair gene PMS2 gene that may be potentially associated with the breast tumor. In conclusion, it remains unclear whether BWS patients have an increased risk of breast lesions or a yet unknown molecular defect is responsible for the rare occurrence of this tumor in BWS. © 2013 Wiley Periodicals, Inc.

Isolated mediastinal amyloidosis is a rare condition. We report an unusual case of amyloid presented as an isolated mass, entirely confined within anterior mediastinum and FDG-avid, mimicking a neoplastic lesion. Because the differential diagnosis included several diseases as lymphoma, a biopsy via mediastinotomy was attended to avoid unnecessary sternotomy. The pathological results diagnosed to be an amyloidosis. The patient was asymptomatic and biopsy allowed an exact diagnosis, thus we decided against the complete excision. No monoclonal gammopathy and/or amyloid deposition were found. Thus, other treatments as high-dose melphalan and/or autologous stem cell transplantation were not indicated.

Sex cord-stromal tumors of the pediatric testis present diagnostic and therapeutic challenges. This study examines the clinicopathologic features of 16 testicular sex cord-stromal tumors from children less than 18 years of age. Four juvenile granulosa cell tumors and five tumors of Sertoli or incomplete differentiation in this study had high mitotic rates and/or sarcomatoid areas that suggested malignancy, but none of these children developed recurrence or metastases. Some of these tumors had been initially misdiagnosed as yolk sac tumors or rhabdomyosarcomas because of the presence of areas superficially resembling these neoplasms. These morphologic pitfalls have received little attention in the literature. Even incompletely differentiated sex cord-stromal tumors have at least focal areas characteristic of juvenile granulosa or Sertoli cell differentiation. In addition, immunohistochemical negativity for alpha-fetoprotein, muscle specific actin, and desmin are useful for ruling out yolk sac tumor and rhabdomyosarcoma. Four patients had Leydig cell tumors and three had large cell calcifying Sertoli cell tumors. Children with Leydig cell tumors are not at risk for metastasis, but children with large cell calcifying Sertoli cell tumors are at risk for endocrine syndromes as illustrated by one of our cases. The differential diagnosis of these tumors is also discussed.

Background. This study assessed the prognostic effect of lymphatic and blood vessel invasion (LVI and BVI) on survival in a retrospective sample of 1408 patients with breast cancer. Methods. Survival analysis was evaluated by univariate (Kaplan-Meier product limit method and log rank test) and multivariate (Cox model) analysis. Correlations among variables were studied by contingency tables and statistical significance was evaluated by chi-square test. Results. Lymphatic vessel invasion was present in 34.2% of cases, and BVI in 4.2%. Lymphatic vessel invasion correlated with BVI (P < 0.0001), and both were correlated with metastatic axillary lymph nodes and increasing tumor size and grade; BVI was sporadic (only 10 cases) among lymph node negative patients. Although LVI was more frequent among premenopausal patients and those with ductal carcinomas, BVI was unrelated to menopausal status and tumor type. Lymphatic vessel invasion and BVI were associated with poor survival by univariate analysis (P < 0.0001). By multivariate analysis, relative risk of death was significantly increased when LVI was present both in the whole series as well as in the lymph node negative and lymph node positive subgroups; the prognostic role of LVI was independent of menopausal and lymph node status, tumor size, tumor grade, or adjuvant treatment. In the lymph node negative sample, LVI had strong prognostic power. In the lymph node positive sample, the prognostic role of LVI was also independent of the number of lymph nodes with metastases. Blood vessel invasion had no prognostic role in any subgroup. Conclusion. The prevalence of BVI was particularly low in this study, and the question of its possible prognostic role for patients with breast cancer should be assessed with methods that amplify its detection. LVI is a strong prognostic factor for operable patients with breast cancer. In lymph node negative patients, LVI is a predictor of poor prognosis for those who are consequently candidates for adjuvant therapy. Similarly, in lymph node positive patients, LVI is a predictor for a high risk of death for those who are candidates for highly intensive adjuvant strategies. Cancer 1995; 76:1772–8.

Two cases of fibromatosis of the breast, characterized by a proliferation of spindle cells containing intracytoplasmic, spherical, eosinophilic inclusion bodies, are reported. The light and electron microscopic features, as well as the immunohistochemical features, are indistinguishable from those found in infantile digital fibromatosis. The proliferating spindle cells are characterized as myofibroblasts, whereas the inclusion bodies show an immunohistochemically nonreactive, hollow-like pattern with peripheral reactivity for actin filaments. This lesion, observed for the first time in the breast, expands the number of extradigital inclusion body fibromatoses.

We analysed the immunohistochemical expression pattern of the distinct carbohydrate epitopes of the TAG-72 molecule, defined by the monoclonal antibodies (MAbs) B72.3, CC-49 and CC-83, in 92 breast carcinomas of different histological type, and in other histological components identified in the mammary tissue samples studied. The results were correlated with the clinico-pathological characteristics of the tumours, and with their proliferative activity, assessed by thymidine labelling index (TLI). Expression of the TAG-72 epitopes was detected in all the tumour histotypes analysed, but patterns of immunoreactivity tended to vary in relation to type and level of differentiation. The comparative analysis of the reactivities of the three anti-TAG-72 MAbs revealed differences in their ability to recognise neoplastic lesions. MAb CC-49 reacted with the highest percentage of tumours (82\%), and also tended to yield the highest percentages of immunoreactive cancer cells, while B72.3 and CC-83 reacted with lower percentages of tumours (respectively, 55 and 51\%), and identified lower percentages of immunoreactive cells. High levels of expression of the three TAG-72 epitopes were detected in areas of in situ ductal carcinoma. Comparatively lower levels of immunohistochemical positivity were found in atypical epithelial hyperplasia, normal mammary epithelium and epithelium with cystic disease. TAG-72 epitope expression was correlated with prognostic parameters. The synchronous expression of the three epitopes significantly correlated with large tumour size (> 2 cm), and with high histological grade. No correlations could be demonstrated between TAG-72 phenotypes and nuclear grade, lymph node status and proliferative activity (high versus low).

Fine-needle aspiration (FNA) diagnosis of oncocytic lesions is challenging. In fact, oncocytic changes occur in inflammatory, hyperplastic, and neoplastic settings, including both benign and malignant tumors. The rare oncocytic variant of papillary thyroid carcinoma (PTC), shows papillae composed by cells with large oncocytic granular cytoplasm featuring clear PTC nuclear features. A morphological similar, but biologically distinct lesion, is the encapsulated papillary oncocytic neoplasia. Here, we first report on FNA, its cytological features together with histological, immunohistochemical, and molecular correlates. Diagn. Cytopathol. 2011;. © 2011 Wiley-Liss, Inc.

This study reports a series of 19 extrapleural solitary fibrous tumors. The patients included 6 men and 13 women with age ranging from 27 to 86 years. Three patients showed local recurrence. In 2 tumors, a diagnosis of malignancy was made. All of the tumors were strongly positive for CD34, and 3 of them expressed high levels of progesterone receptor. Solitary fibrous tumors are fairly rare, occurring in many parts of the body, and their behavior is unpredictable.

Aim The use of a non-toxic tyrosine kinase receptor inhibitor, Imatinib Mesylate (IM), has become an ever-more common therapeutic alternative in some Kit (CD117) over-expressing neoplasms. As the treatment eligibility for these drugs hinges on CD117 expression, Kit immunostaining has recently been widely examined in various tumours. There are only limited data in the literature on the expression of c-kit expression in Wilms' Tumour. We examined CD117 expression in Wilms' tumour in order to correlate this marker with clinico-pathological data and to clarify its prognostic impact. Methods This study included 40 cases of Wilms' tumour. Sections from paraffin-embedded tumour samples were immunostained by standard ABC technique using c-kit polyclonal antibody with antigen retrieval. Results and conclusions In the case of C-kit positive examples, the staining was focal, with patch distribution. On univariate analysis, significantly higher c-kit expression was observed in neoplasms in a more advanced stage of development than those in a less advanced stage ( p =0.0055). In addition, over-expression of this marker was significantly correlated with the death of patients ( p =0.0294) and recurrences of disease ( p =0.0118). Moreover, all our Wilms' tumour anaplastic subtypes showed over-expression of c-kit and this was significantly higher than in favourable histology examples ( p =0.0182). The results of multivariate analysis, instead, did not reveal any correlation of c-kit expression and prognosis. In our opinion these results could be due to the number of cases considered which is not particularly high. However, it seems likely that c-kit expression could be a secondary event related to tumour progression and could be influenced by chemotherapy and unfavourable histology.

BackgroundGastrointestinal stromal tumors (GIST) exhibit an unpredictable clinical course and can rapidly progress to lethality. Predictions about the biological behavior of GIST are based on a number of canonical clinical and pathologic parameters whose validity in distinguishing between a benign and a malignant tumour is still imperfect. The aim of our study was to investigate the role of morphologic parameters and expression of cells cycle regulators as prognosticators in GIST.MethodsWe performed an immunohistochemical analysis for Ki67, p27Kip1, Jab1, and Skp2, on a Tissue Microarray (TMA) containing 94 GIST. Expression of the above proteins was correlated to classically used prognosticators, as well as to risk groups. Clinical significance of histologic and immunohistochemical features were evaluated in 59 patients for whom follow-up information was available.ResultsOverexpression of Ki67 and Skp2, and p27Kip1loss directly correlated with the high risk group (p = 0.03 for Ki67 and Skp2, p = 0.05 for p27Kip1). Jab1 expression did not exhibit correlation with risk. In 59 cases provided with clinical follow-up, high cellularity, presence of necrosis, and Ki67 overexpression were predictive of a reduced overall survival in a univariate model. The same parameters, as well as mitotic rate, tumour size, and p27Kip1loss were indicative of a shortened relapse free survival interval. High cellularity, and high mitotic rate retained their prognostic significance by multivariate analysis.ConclusionOur data suggest that a number of histologic parameters in combination with immunohistochemical expression of cell cycle regulators can facilitate risk categorization and predict biologic behavior in GIST. Importantly this study demonstrates, for the first time, that Skp2 expression correlates with Ki67 expression and high risk in GIST.

Primary childhood germ cell tumors (GCTs) represent a rare and heterogeneous group of tumors that varies in histologic differentiation, age of presentation and clinical outcome. In malignant neoplasms, apoptosis is a prognostic marker and a predictive factor of response to therapy. Therefore, the study of the expression and mutation of molecules involved in the regulation of apoptosis could be useful in order to both predict the clinical outcome and design self-tailored therapeutic approaches. We retrospectively analysed tissue samples of 54 childhood GCTs. The expression of p53 and BAX protein was assessed by immunohistochemistry (IHC). Moreover, we investigated the presence of mutations in the BAX and p53 genes SSCP-PCR and direct sequencing. IHC analysis of BAX protein expression showed that 14 out of 54 tumors (26%) had no BAX protein expression, in the remaining 40 patients (74%) the intensity of BAX was low in 20 patients (37%) and high/intermediate in 20 (37%). BAX was mutated in 6 patients. p53 was expressed in 43 patients (79.6%), was not detectable in the remaining 11 (20.4%) and mutated in only 3 patients. p53 mutational status and expression were not correlated to the overall survival (OS). On the other hand, both IHC score and mutations for BAX were correlated to sacrococcygeal primary localization. BAX mutations were inversely correlated with OS (p=0.0419) while BAX IHC intensity was directly correlated with OS (p=0.0376). The stratification for histotype showed a direct correlation between BAX IHC and OS in both immature teratoma (p=0.045) and mixed malignant GCT (p=0.010) while the correlation was lost in mature teratoma (p=0.300). These results indicate that both mutations and BAX protein levels are useful molecular biological markers for prognosis and clinical management of pediatric GCT.

Objective: Recurrence of apparently completely resected benign meningiomas is a rather frequent event, the mechanisms of which are still unclear. The aim of this study is to define the pathological features, proliferation indexes, growth factors and hormone receptor expression in predicting the meningioma recurrence. Methods: Two groups of 50 completely resected benign WHO I meningiomas, with and without recurrence respectively, have been reviewed. Tumor location, consistency, vascularity, and histological types have been considered. Immunohistological studies include mitotic index (MI), Ki-67 LI, estrogen and progesterone receptors (ER and PR), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and Bcl-2. All these factors have been correlated with the recurrence. Results: The tumor recurrence was not correlated with the patient age, tumor location, consistency, vascularity and histology. There was not difference in the histological pattern between local and diffuse recurrences. M.I. and Ki-67 LI were significantly correlated with the recurrence (P

We report 62 cases of invasive micropapillary carcinoma of the breast characterized by delicate pseudopapillary structures lacking a fibrovascular core and by tubuloalveolar structures freely floating in clear, empty spaces. All patients but 1 were women (median age, 57 years; range, 25–89 years). Tumor size ranged from 0.7 to 10 cm (median, 2.8 cm); 54 (87%) were grade 3. Psammoma bodies were identified in 29 (47%). Focal to massive lymphatic permeation was present in 39 (63%). Architectural features were retained in the node metastases, dermal lymphatics, and recurrences. Fifty-six patients (90%) had metastatic axillary nodes: 18 tumors were estrogen receptor–positive (32%); 11 were progesterone receptor–positive (20%); HER2/neu was overexpressed in 53 (95%) and p53 in 39 (70%). A peculiar immunoreactivity for MUC1 limited to the cytoplasmic membrane oriented toward the stroma and an absence of immunoreactivity for E-cadherin in the same side of the cytoplasmic membrane indicated inversion of cell polarization and a disturbance in the cell adhesion molecules. Of 41 patients with available follow-up, 29 (71%) had local recurrence (mean, 30 months) and 20 (49%) died of disease. These results underscore the aggressive behavior and poor prognosis of this breast carcinoma variant. Aggressive preoperative neoadjuvant chemotherapy should be considered.

Autoimmune lymphoproliferative syndrome is a disorder due to a defect of lymphocyte apoptosis, whose clinical manifestations consist of hyperplasia of lymphoid tissues and autoimmune diseases. We report on a 26-month-old child who presented with frequent eruptions of weals and angioedema without any apparent triggering factor, who subsequently developed an erythematopapular rash with a histological pattern of a lymphoplasmacellular infiltrate. Familial anamnesis revealed a history of lymphoadenomegaly and massive spleen and liver enlargement in her sister. Functional and molecular analysis led to a diagnosis of type 1a autoimmune lymphoproliferative syndrome. Immunophenotyping of the cutaneous lesion revealed the presence of an inflammatory infiltrate with a considerably high number of Langerhans cells. Cutaneous features such as urticaria, angioedema and vasculitis in children with a personal and familial history of hyperplasia of lymphoid tissues may be a presenting sign of a systemic disease, such as autoimmune lymphoproliferative syndrome.

This article describes histopathologica, immunohistologic, and morphometric features of an epithelioid haemangioendothelioma that presented in the breast of a 30-year-old woman. Histologically the tumour was composed of large round, polygonal, slightly spindle shaped endothelial cells lying in a myxoid matrix. The lesion exhibited primitive vasoformation characterized by the presence of cytoplasmic vacuoles. The tumour cells reacted positively to F-VIII related antigen, whereas mammary ducts entrapped by the tumour cells reacted positively with keratin. Although the breast is an unusual location for this type of lesion, epithelioid haemangioendothelioma should be considered a rare differential diagnosis of a breast mass.

We report the history of a pitfall in thyroid histopathology of a 47-yr-old man with a euthyroid nodular goiter involving the right lobe. The ultrasound-guided fineneedle aspiration of the dominant (3 cm) nodule, showing benign-appearing follicular cells, colloid, and scattered Hurthle cells, was consistent with a benign hyperplastic nodule (1). Because the left lobe had not shown evidence of nodular disease, the patient was submitted to a right lobectomy. The pathologist described a heavy lymphoplasmacyticbackgroundwithoccasionalgerminalcenter formation, as observed in Hashimoto thyroiditis, and a microscopic ( 1cm) follicularproliferationofepithelial thyroidcellswhose nucleidisplayedmembrane irregularityandchromatinclearing with occasional grooves. Thus, a histological report of a follicular variant of papillary microcarcinoma was issued. The patient underwent a completion thyroidectomy at the Federico II UniversityofNaples.At thatoccasion, thecompletesetofslides from both surgeries was reviewed by expert pathologists in the field of thyroid disease.

We analysed the differential expression pattern of the three distinct TAG-72 carbohydrate epitopes detected by monoclonal antibodies (MAbs) B72.3, CC83 and CC49 in a consecutive series of 114 patients with primary breast cancer and in 39 synchronous lymph node metastases. B72.3, CC83 and CC49 were expressed in respectively 81 (71\%), 68 (60\%) and 96 (84\%) of the 114 cases. Interestingly, MAb B72.3 was significantly expressed in a subgroup of patients characterised by larger tumour size (p=0.013), lymph node metastasis (p=0.0002), high histopathological grade (p=0.006), high cell kinetics (p=0.04) and advanced clinical stage (p=0.0019). In 20 (51\%) of the 39 pairs of matched primary breast cancers and synchronous lymph node metastases, TAG-72 was expressed in the tumour but not in the corresponding metastatic lymph node; tumours with TAG-72-negative lymph nodes appeared to be clinicopathologically more aggressive. CC49, the most immunoreactive and widely used MAb, was not detected in 34\% of the metastases of expressing primary tumours. All three MAbs were found in a significantly lower per cent of synchronous metastases with respect to primary tumours (p

A case of Kaposi sarcoma with HIV-negative and sequence of HHV-8 positive and exclusive rectosigmoid and descending colon involvement without immunodeficiency is reported. Histologically, in addition to typical features of Kaposi sarcoma, Cowdry type A inclusions were seen. PCR analysis of the tumor showed positivity for human herpesvirus 8. Two of the six reported cases of Kaposi sarcoma limited to the bowel were from African men before the AIDS epidemic. J. Surg. Oncol. 2001;76:197–200. © 2001 Wiley-Liss, Inc.

To the Editor: A 61-year-old man with no symptoms was found to have an enormous mass that occupied the entire right flank and pushed the right kidney down. A preoperative cytologic specimen obtained from a computed tomography–guided fine-needle biopsy showed many huge epithelial cells, with naked or doubled nuclei, suggesting a diagnosis of a clear-cell carcinoma of the right kidney. At surgery, an ovoid mass (24 by 18 cm) distinct from the right kidney was found. After the mass was removed (Figure 1), the appearance of the kidney was normal. A definitive histologic examination showed adrenocortical carcinoma (Figure 2). The . . .

Summary Ten cases of breast hamartomas were reviewed; the patients' age ranged from 31 to 55 (mean 40.4, median 39). All cases presented with a palpable, sometimes tender, lump. The typical mammographic feature was a well defined, round to lens shaped, variable dense mass, occasionally surrounded by a thin radiolucent zone. All hamartomas were unilateral (4 in the right and 6 in the left breast, respectively) and no recurrence occurred after local excision. The tumor size ranged from 5 to 150 mm (mean 54 mm). Histologically all hamartomas were composed of a typical fibrous, adipose and glandular tissue combination. Immunohistochemically there was a strong positivity for cytokeratin and epithelial membrane antigen in the epithelial cells, a positive finding for vimentin and muscle-specific actin in stromal and myoepithelial cells, and for S-100 protein in myoepithelial cells. Vessels endothelial cells were immunoreactive for Factor VIII. Immunohistochemical analysis of hormone receptors completed on formaldehyde-fixed paraffin-embedded specimens, showed estrogen and progesterone receptors positivity in 9 cases and estrogen positive progesterone negative receptors in one case. In all cases the receptorial positivity was limited to the epithelial elements. These data revealed that 1) breast hamartoma is a benign, tumor-like lesion, histologically dissimilar from other lesions such as fibroadenoma and pseudoangiomatous hyperplasia; and 2) hamartoma tissue is influenced by hormones like the surrounding normal breast parenchyma.

0 RTHOTOPIC liver transplantation (OLT) is the only clinically effective treatment for fulminant or chronic liver failure, whether genetic in origin or due to acquired hepatocellular dysfunction. However, wider application of OLT is limited by organ shortage and a relatively high mortality rate. Consequently, there is increasing interest in hepatocyte transplantation, especially in the treatment of metabolic disorders, or, in combination with plasmapheresis, of fulminant hepatic failure (bioartificial liver).’ With genetic defects, it may be possible to introduce genes into hepatocytes before autotransplantation. In recent years, the spleen has been the most popular site for inoculation of hepatocytes in experimental studies. Several authors have reported good survival and function,‘.” but problems remain in respect to long-term survival, ccl1 proliferation and differentiation, and the provision of sufficient number of cells to support failing liver function. Additionally, with one exception,4 most studies have been performed in the rat, and there has been little work carried out in large mammals. In order to address these concerns, we describe a method of autotransplantation in the pig which simplifies the surgical procedures and allows estimation of hepatocyte proliferation and survival in the spleen.

A new case of breast tumor with features of eccrine spiradenoma is described. This neoplasm is exceedingly rare, because only two cases, arising in breast parenchima, have been previously reported. The patient was a 43-year-old woman and she experienced three local recurrences at 7, 20, and 30 months from the first excision. No distant metastases were observed. Microscopically, the tumor was circumscribed and showed a lobulated pattern. Neoplastic lobules consisted of packed, monotonous, basaloid epithelial cells with round to ovoid nuclei and scant cytoplasm. At the periphery, the lobules were delimitated by smaller cells with dark nuclei. Immunohistochemical reactivity in tumoral cells was found for both cytokeratin and epithelial membrane antigen; vimentin, muscle-specific actin, glial fibrillary acidic protein, S-100 protein, and carcinoembryonal antigen were all negative. Furthermore, the lesion showed a diffuse positivity for estrogen and progesterone receptors and a high growth fraction labelled by MIB-1 (Ki-67) antibody. These findings, in conjunction with the deep location of the tumor, suggest an origin of the neoplasm from the breast epithelium. Because of a potential local aggressive behavior, the excision of a wide rim of uninvolved breast tissue is recommended.

Most of the data regarding the significance of c-erbB-2 oncogene expression as a prognostic marker in breast cancer have been generated in many large retrospective studies by retrieving the corresponding oncoprotein in archival paraffin embedded sections. Recently, employing fresh breast cancer cells obtained by means of fine-needle aspiration biopsy, we found a rate of c-erbB-2 positive breast tumors (58\%) higher than that reported in paraffin-embedded tissue sections by others studies. The present analysis was undertaken to investigate the impact of routine tissue processing on the preservation of the c-erbB-2 immunoreactivity. This issue was addressed by assessing the relative rate of c-erbB-2 oncoprotein immunodetection on FNAB smears and matched surgical specimens of breast cancer. The expression of c-erbB-2 oncoprotein was evaluated using the alkaline phosphate-anti-alkaline phosphatase (APAAP) technique in 54 breast aspirates and corresponding surgical specimens of primary breast cancer. Twenty-six (48\%) smears and 23 (43\%) matched paraffin sections gave specific signal for c-erbB-2 oncoprotein. The slightly higher incidence of c-erbB-2 expression found on smears seems to be mainly due to the better antigen preservation in the fresh cytological preparations. We conclude that routine histological processing may affect c-erbB-2 immunoreactivity; therefore, in mounting prospective studies, it is advisable to assess c-erbB-2 status in fresh tissue. Moreover, the assessment of c-erbB-2 expression on aspirate samples may yield additional information to the pre-surgical prognostic evaluation of breast cancer diagnosed by FNAB.

Paraffin-embedded tissues are used in retrospective studies to evaluate the prognostic significance of DNA-flow cytometry (DNA-FCM) in human breast cancer. Although paraffin-embedded samples yield information on disease-free survival (DFS) and overall survival (GAS) of homogeneously selected patients, the resulting DNA-histograms have a lower resolution of aneuploid subpopulations and higher debris levels than those of fresh tumor samples. The aim of this study was to evaluate, retrospectively, the prognostic value of ploidy and the S-phase fraction (SPF) using 515 samples of paraffin-embedded consecutive primary breast cancer tissue (median follow-up: 75.4 months). Ploidy was detectable in 89% cases (34% diploid and 66% aneuploid) and SPF in 77%. The optimal cut-off for SPF was 6%. High SPF values were significantly correlated with shorter DFS (p=0.028) and OAS (p=0.018); aneuploidy was significantly correlated only with a shorter OAS (p=0.0058). Using the Cox proportional hazards regression model to evaluate the independence of DNA-FCM derived parameters, only high SPF was able to predict both a shorter DFS (p=0.02) and OAS (p=0.002). Furthermore, high SPF values were found correlated to aneuploidy (p

Our study was prompted by the observation that a large number of patients with DTC attending our hospital were from the area around the volcano Mt. Vesuvius (Campania, Italy). In an attempt to shed light on a possible association between volcanoes and DTC, we retrospectively examined 500 new cases admitted to the University of Federico II of Naples in Campania from 2000 to 2009. Age, sex, tumor size, lymph-node invasion, distant metastases, and cancer histotype were analyzed. We recorded the place of birth and of residence of each patient.In conclusion, we found a higher risk of papillary thyroid cancer and an earlier onset of this disease in the Vesuvius area than in other areas of Campania, although the risk was not as high as around Mt. Etna

We report a case of pilomatrix carcinoma in a 42 year old woman. The patient presented a rapidly growing 4-cm subcutaneous mass in the right preauricular area. She was free of recurrence 24 months after surgery. Immunoreactivity was studied for cytokeratins, epithelial membrane antigen, S-100 protein, blood group antigens, Leu-M1, β-2-microglobulin, vimentin, neuron-specific-enolase and cellular binding for peanut agglutinin. Squamous cells were reactive for cytokeratin AE1/3, epithelial membrane antigen, blood group antigens B and H, and peanut agglutinin. Basaloid cells were focally reactive for cytokeratin AE1/3 and epithelial membrane antigen. Flow cytometry revealed a euploid DNA content and a high proliferative rate of the pilomatrix carcinoma and in benign pilomatrixoma studied for comparison. The pathological diagnosis must be based on histomorphological criteria.

The diagnostic accuracy of frozen section (FS) examination and intraoperative cytology (IOC) has been compared in two different series of breast biopsies in which only one of the two methods has been used. The intraoperative results have been compared with the final histological diagnoses. Five-hundred-ten cases have been investigated by using FS only, and 407 by means of IOC. The two series were comparable because they included the same pathologies; moreover we have subdivided each series into four groups of pathologies to better evaluate the diagnostic accuracy of two methods. The total diagnostic accuracy of FS has been 93.13% vs. 95.-33% of IOC The value of diagnostic accuracy of FS and IOC in the four sub-groups substantially overlapped; there was only a little difference in the group of “various lesions” in which the diagnostic accuracy of IOC was higher. No false positive has been observed in IOC. FS have produced one false positive (0.19%), whereas false negatives have amounted to 1.77% for IOC and to 1.72% for FS. Deferred diagnoses have been 2.95% in IOC and 4.90% in FS examination. For both methods according to Galen and Gambino the following values have been calculated: sensitivity, specificity, efficiency, and predictive value. By comparing the data, the value of the cytological examination in the intraoperative diagnoses results is evident mainly when the latter is coupled with the gross observation. Causes of diagnostic errors clearly overlap both in IOC and in FS: (1) lesions with a fibroadenomatous appearance can involve an overdiagnosis or an underdiagnosis; (2) low-grade lesions like tubular carcinomas or in situ lobular carcinomas can be interpreted as benign; (3) the differential diagnosis of intraductal lesions may be very difficult, and a conservative approach is the best choice; and (4) infiltrating lobular carcinoma may be neglected both in FS and IOC. The few disadvantages of the cytologic method are offset by its low cost, the wider sampling, the possibility of sparing tissue for further investigations (such as steroid receptors, cellular kinetic, electron microscopy, and other biological studies) proved more useful in prognostic evaluation of breast cancer.

The adenoid variant of squamous cell carcinoma has been well-documented in several anatomic sites, including the skin. This tumor is characterized by acantholytic arrays of neoplastic keratinocytes that form pseudoglandular profiles. Although it is typically confused with adenocarcinomas, adenoid squamous cell carcinoma also may be mistaken for malignant vascular proliferations. This report concerns six acantholytic cutaneous squamous cell carcinomas that closely simulated angiosarcomas on conventional histologic examination. They arose in sun-exposed skin areas in middle-aged or elderly patients (mean age, 60 years), five of whom were men. In contrast to the typical clinical appearance of angiosarcoma, pseudovascular adenoid squamous cell carcinoma presented itself as a discrete cutaneous ulcer or crusted tanpink nodule. Microscopically, this lesion was characterized by interanastomosing cordlike arrays of polygonal or flattened tumor cells, with internal pseudolumina that contained detached tumor cells. A connection between the dermal neoplasm and the epidermis was apparent in three cases, but it was focal. Erythrocytes were seen in pseudovascular spaces in five tumors. Immunohistochemically, all examples of pseudovascular adenoid squamous carcinoma were reactive with antibodies to cytokeratin and epithelial membrane antigen (EMA). In addition, three expressed vimentin, two exhibited blood group antigen-positivity, and two bound Ulex europaeus I agglutinin. None of them was immunoreactive for Factor VIII-related antigen, and two of three studied for CD34-reactivity were likewise negative. A control group of six cutaneous angiosarcomas was uniformly nonreactive for cytokeratin and EMA, but they showed positivity for vimentin, Ulex binding, and CD34 positivity in all instances. Pseudovascular adenoid squamous cell carcinoma may be distinguished effectively from angiosarcoma of the skin by attention to its clinical features and by appropriate immunohistochemical studies. These two tumors differ in biologic behavior; three patients with pseudovascular adenoid squamous cell carcinoma died of their tumors, whereas all angiosarcomas in this series proved fatal.

Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 19.5 years). Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses. Gross examination showed that they were solid, cystic, and hemorrhagic. Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases. Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae. Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found. Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein. None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers. Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common. No diagnostic secretory granules were found. DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 1.1) DNA content in one case. Fourteen patients with follow-up were free of disease (mean, 2.6 years). Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation.

Six cases of intestinal ganglioneuromatosis (GN) included in this study reveal the occurrence of two morphologic patterns. Transmural GN was characterized by neural hyperplasia in all layers of the bowel wall with predominant involvement of the myenteric plexus. It was found in three patients affected by multiple endocrine neoplasia IIb. Mucosal GN, having predominant involvement of the mucosa without concomitant hyperplasia of the myenteric plexus, was associated with von Recklinghausen's disease, adenocarcinoma of the colon, and multiple adenomas with megacolon in one case each. Clinicopathologic correlations and review of the literature suggest that mucosal GN might represent a distinct entity with a lower morbidity rate than the transmural variant. Immunohistochemical stains reveal considerable heterogeneity. S-100 protein, neuron-specific enolase, and synaptophysin immunostaining followed the distribution of the nervous hyperplasia in the different intestinal layers as identified morphologically and allowed precise determination of the proliferating cells. Increased reactivity for vasoactive intestinal polypeptide, opioid peptides leu-enkephalin and met-enkephalin, and substance P was present in all cases with transmural involvement; mucosal GN showed normal reactivity for opioid peptides and focal increased staining for substance P (one case) and vasoactive intestinal polypeptide (two cases) in the lamina propria. Mild increased immunoreactivity for tyrosine hydroxylase was present in the myenteric plexus of four out of four cases. Histochemical determination of acetylcholinesterase, performed in one case of transmural type, demonstrated hyperplasia of parasympathetic fibers and neurons. Electron microscopic study of another case suggested the presence of several neurotransmitters. These results indicate that the physiopathology of GN is related to a complex hyperplasia of several peptidergic, cholinergic, and probably adrenergic nerve fibers instead of a selective overgrowth of one type of nerve fiber.

We describe a malignant pelvic tumor with rhabdoid-like features that arose in the sacroiliac region of a 15-year-old girl. Fine-needle aspiration (FNA) cytology showed large cells with glassy cytoplasm, globular hyaline cytoplasmic inclusions, and prominent nucleoli. Immunocytochemical methods applied to FNA material revealed immunoreactivity for cytokeratin, epithelial membrane antigen, and vimentin; the cells failed to react with antibodies to desmin. This distinct appearance and phenotype was most consistent with a diagnosis of extrarenal malignant rhabdoid tumor. Electron microscopy confirmed this interpretation, showing whorled filamentous aggregates in the cytoplasm of the tumor cells.

Twenty cases of inflammatory myofibroblastic tumor (IMT) were studied; 19 involved the lung and 1 the esophagus only. The patients' ages ranged from 3 to 72 years. There were 9 males and 11 females. Involvement of a bronchus was seen in one case and of mediastinal structures in four. Chest pain and dyspnea were common symptoms; eight patients were asymptomatic. Seven patients underwent lobectomy, 12 local excision, and 1 biopsy alone. The lesions were nonencapsulated and ranged from 1.2 to 15 cm. Various proportions of plasma cells, histiocytes, and spindle cells were observed; the latter corresponded ultrastructurally to fibroblasts and myofibroblasts, were immunoreactive for vimentin and actin and focally for desmin, and were negative for epithelial markers. Plasma cells were polyclonal for light chains. One patient had two recurrences, and in one case a large pleural IMT was found eight years after the excision of a similar lesion in the lung. All patients with follow-up (ten) were well as long as ten years after the diagnosis (average, 3.7 years).

Sixteen cases of congenital mesoblastic nephroma (CMN) were studied. The tumors showed variable patterns of growth, degrees of cellularity, and mitotic activity. Six tumors had the classical pattern of CMN, seven were of the cellular or atypical variant and three showed combined features. The mean ages at presentation were 16 days, 5.3 months, and 2.3 months, respectively. Average size and weight were 5.1 cm and 94 g for classical CMN, 9.1 cm and 620 g for cellular CMN and 10.5 cm and 150 g for combined tumors. Cyst formation, hemorrhage and necrosis were confined to cellular CMNs and to cellular areas of combined CMNs. Mitotic activity ranged from 0 to 110 high-power fields (HPFs) in classical tumors to 25 to 3010 HPFs in cellular tumors. Clear cell sarcoma-like areas were observed in three neoplasms. In ten cases there was invasion of perirental fat; in one case each, invasion of the psoas muscle, renal vein wall, and renal vein lumen was observed. Ultrastructural and immunohistochemical studies showed features consistent with myofibroblastic differentiation. Flow cytometric analysis revealed euploidy in one classic CMN, one cellular CMN and in classic areas of a combined CMN; cellular areas of the latter tumor were aneuploid. All patients with follow-up were alive without evidence of disease after a mean period of 5 years following nephrectomy alone. No correlation was observed between the pathologic features assessed and the biologic behavior of these neoplasms.

Cutaneous adenoid squamous carcinoma (ASCC) is a distinctive neoplasm featuring tumor cell acantholysis. Because this lesion occasionally may prove troublesome diagnostically, we studied the clinical, histologic, and immunohistochemical features of 55 examples in order to further elucidate its characteristics. ASCC most often occurred in the skin of the head and neck in elderly patients. Of 49 patients in this series, 46 were men and 3 were women; their ages at diagnosis ranged from 25 to 90 yr, with a mean of 71. Six individuals had 2 metachronous neoplasms. ASCC generally behaved in an indolent manner, although 19\% of cases did metastasize widely and prove fatal. Tumor size of greater than 1.5 cm appeared to correlate with the risk of an adverse clinical outcome. In addition, 10 patients with ASCC of the skin subsequently developed visceral malignancies. The cutaneous neoplasms were typified by invasive, tubular or pseudoglandular profiles of polygonal cells in the dermis, with glassy eosinophilic cytoplasm and focal squamous pearl formation. Connections to the overlying epidermis were commonly apparent. Immunohistochemically, ASCC demonstrated uniform reactivity for cytokeratin, but lacked markers of specialized glandular cells. These findings militate against the interpretation that such tumors demonstrate partial adnexal differentiation, and show that immunohistology may prove helpful in the differential diagnosis between ASCC and primary or metastatic adenocarcinomas of the skin.

The recognition of myogenic differentiation is not always possible using routine light or electron microscopic techniques. In this article, we describe our experience with two small round-cell neoplasms occurring in young children, each of which exhibited an undifferentiated light microscopic appearance. In both cases, myogenic features were revealed by immunocytochemical methods applied to fine-needle aspiration (FNA) biopsies. Each was immunoreactive for desmin and vimentin and failed to react with antibodies to leukocyte-common antigen. Moreover, formalin-fixed tissue sections of one case were negative for cytokeratin and epithelial membrane antigen. Sporadic reactivity for neuron-specific enolase and Leu-7 antigen was observed in occasional cells in FNA specimens, but synaptophysin was not identified. The rapidity of the method and the reliability of the immunocytochemical findings, when compared with routine cytologic evaluation, emphasize the diagnostic utility of immunocytochemical analysis when FNAs of pediatric soft-tissue tumors are obtained.

The first case of plasma cell granuloma (PCG) of the breast is presented. The lesion was seen as a circumscribed firm mass in the right breast of a 29-year-old woman. Histologically, a prominent plasma cell infiltrate was seen in a fibrous hyalinized stroma that contained spindle- and large stellate-shaped stromal cells with bizarre nuclei. Immunohistochemical study demonstrated the polyclonal nature of the plasma cells and characterized the stromal cells as myofibroblasts. The nature of these cells was confirmed ultrastructurally. PCG of the breast should be considered analogous to inflammatory pseudotumors of the lung and extrapulmonary sites.

An autoimmune hemolytic anemia has been detected in a patient suffering from a dermoid cyst of the mesentery. Early recognition of the teratoma is important, since only removal of the tumor is consistently curative. Investigations showing immunocompetent cells within the cyst's wall lend further support to the contention that the tumor tissue itself produces, for reasons yet unknown, antitumor autoantibodies that could cross-react with the patient's erythrocytes. The role of computerized tomography (CT) in the diagnosis of abdominal teratoma is emphasized, since CT has permitted visualization of the cystic structure of the tumor before the surgical removal of the mass.

The authors present a case of exophthalmos caused by invasion from a hypo-physeal tumour, rare both for this type of metastasis and for the patient’s young age. Histological study of biopsy material enabled the tumour to be classified. Comparison of clinical and microscopic data helps towards a better understanding of the behavioui of invasive adenomas.

The clinical course and the pathologic features of 29 patients with the prune belly syndrome (PBS) are reviewed. There were 26 males and 3 females. In addition to the classical triad of deficient abdominal musculature, urinary tract abnormalities, and cryptorchidism, a broader spectrum of other defects was found including musculoskeletal (58\%) and gastrointestinal (31\%) abnormalities. Genital anomalies were present in all three female patients. Many of these defects may be inapparent at birth, but are the cause of morbidity and mortality later in life. Severe urinary tract maldevelopment and pulmonary hypoplasia as part of the oligohydramnios syndrome was the most common cause of perinatal deaths. In these patients, major portions of the renal parenchyma were dysplastic, but in survivors, renal dysplasia, when present, was minor by comparison, and affected less than 1/3 of the parenchyma. Although several questions remain unanswered, we believe that the PBS results from the effect of one or more teratogenic agents on the somatic mesoderm, producing inappropriate mesenchymal development and inadequate mesenchymal-epithelial interactions that lead to abnormal development and dilatation of some of its derivatives (abdominal muscles, ureter, bladder, prostate, urethra, and gubernaculum). Although abnormalities in derivatives of the intermediate mesoderm (kidney) may also be produced by the injurious agent(s), they are more likely a result of urinary obstruction. Abnormalities in other organs and systems are the consequence of oligohydramnios.