Uterine PEComa with aggressive behavior: A review with an additional case of spontaneous vaginal expulsion.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor originating from perivascular epitheloid cells showing melanocytic and smooth muscle differentiation. The uterus represents the second most common site of origin. A 49 years woman presented to our Hospital for a vaginal spontaneous expulsion of a mass suggestive for malignant mesenchymal tumor. The patient underwent total hysterectomy and bilateral salpingo-oophorectomy and the histopathological report was compliant with a PEComa with aggressive behavior. Medical Literature databases about PEComa were searched. The current literature identified near 90 cases of uterine PEComas and they are categorized as uncertain malignant potential or with aggressive behavior. Primary surgical excision represents the gold-standard treatment. Recently targeted therapy with mTOR inhibitors has been introduced with an important beneficial. In this paper we review the Literature about the uPEComa with aggressive behavior reporting the first case of spontaneous vaginal expulsion.

CROCC-mutated rhabdoid colorectal carcinoma showing in intercellular spaces lamellipodia and cellular projections revealed by electron microscopy.

BACKGROUND: Rhabdoid colorectal carcinoma (RC) is a rare lesion localized to the proximal colon of patients with a mean age at diagnosis of around 70 years. This tumor shows an aggressive behavior with an overall survival period shorter than 12 months. The diagnostic hallmark is the presence of rhabdoid cells. Alterations in chromatin remodeling (SMARCB1) and in the centrosome structure (CROCC) are reported in RC usually BRAFmut and MSI-H. RKO intestinal neoplastic cells culture (BRAFmut, SMARCB1wt, MSI-H) with CROCC knockdown exhibit rhabdoid features and develop prominent projections from the edge of the cell. METHODS: Here, we investigated two cases of CROCCmutSMARCB1wt RC by scanning and transmission electron microscopy (SEM, TEM). RESULTS: TEM confirmed the diagnostic presence of intermediate cytoplasmic filaments and nucleolar margination. SEM showed cellular protrusions (lamellipodia) in the intercellular spaces not evident at light microscopy. CONCLUSIONS: These protrusions CROCC-related might represent the pathogenetic mechanism underlying the rhabdoid aggressive behavior, independently of tumor staging. To our knowledge, the SEM technique was applied in the study of this neoplasm for the first time.

Oil Red O Is a Useful Tool to Assess Donor Liver Steatosis on Frozen Sections During Transplantation.

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. METHODS: Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 µm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. RESULTS: Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. CONCLUSIONS: Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

Fast Chromotrope Aniline Blue Special Stain Is a Useful Tool to Assess Fibrosis on Liver Biopsy During Transplantation.

BACKGROUND: Assessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis. MATERIALS AND METHODS: Twenty consecutive intraoperative donor liver biopsy specimens were evaluated by a pathologist at the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service. The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6 (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB special stain. After a 3-week washout period, only the slides stained with H&E were re-assessed for fibrosis stage by the same pathologist blinded to donor patient data. RESULTS: Combination H&E-CAB staging fibrosis score was higher in 20%, lower in 10%, and the same in 70% of biopsy specimens as determined using only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain alone. CONCLUSIONS: CAB staining may be performed on frozen tissue from liver biopsy during a transplantation process without a significant delay in diagnosis. Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

Neurological complications prevalence and long-term survival after liver transplantation.

INTRODUCTION: Neurological postsurgical complications are a significant cause of morbidity and mortality occur in transplant recipients impacting their survival. METHODS: We analyzed the medical records of 269 patients who underwent transplantation between 2000 and 2011, after application of the exclusion criteria Neurological complications were examined according to the period in which they appeared: immediate (1-30 day) early (31-180 days), and late (after 180 days). The survival analysis was based on the first complication. RESULTS: The majority of transplant recipients were males (73.2%) and white (97.1%) with an overall median age of 49 (range, 18-73) years. Regarding the etiology for transplantation, the most common causes were hepatitis C virus (56.5%) and alcohol (33.1%). Complications, appearing in 29.4% (immediate), 31.5% (early), and 39.1% (late) cases, were encephalopathy, confusion, tremors, headache, and stroke. Patients who had the first complication between 1 and 6 months showed greater mortality than those who had one after 6 months. CONCLUSIONS: Neurological complications led to longer hospital stays with greater early morbidity and mortality. Knowledge of these complications appears to be extremely important for the multidisciplinary transplantation team to decrease its prevalence as well as to diagnose and treat early.

Venous invasion detection in colorectal cancer: which approach, which technique?

Colorectal cancer is one of the most commonly diagnosed human malignancies and is a major cause of death worldwide. A high-quality macroscopic examination and histopathology report enables correct tumour staging, affects patient prognosis, and provides indications for further therapy. Although venous invasion is a stage-independent indicator of poor prognosis that identifies high-risk patients for visceral metastases, it is not a stage-influencing factor. Accordingly the use of special stains to facilitate the detection of venous invasion is not universally recommended and therefore not widely used in routine histopathological analysis. In this report based on a case presentation, the different approaches and techniques for detecting venous invasion are presented and discussed.

Acute juvenile pityriasis rubra pilaris: a case report after mononucleosis infection.

A 24-year-old male boy presented dermatosis which first appeared acutely after an infection at age 17. Clinical and histopathologic examinations were consistent with a diagnosis of juvenile pityriasis rubra pilaris type III. Treatment with UVB narrow-band led to complete resolution of the dermatitis within 1 year. Pityriasis rubra pilaris is a papulosquamous disorder of unknown etiology, which can be treated with retinoids, methotrexate, cyclosporine, and narrow-band phototherapy.

Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma.

AIMS: Survivin is expressed in neoplastic cells and appears to be associated with resistance to therapy and shorter survival in various types of tumours. The aim of the present study was to determine whether nuclear or cytoplasmic expression of survivin is related to disease recurrence and overall survival of patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. METHODS AND RESULTS: Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of primary cutaneous melanoma from 50 patients. Survival rates were estimated using the Kaplan-Meier method and compared using the log rank test. Association of clinical variables (gender, age, tumour location, thickness, Clark level and AJCC stage) with survivin expression was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for survivin had an increased risk of disease recurrence during the first three postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic immunoreactivity was not correlated with either survival or clinical variables. CONCLUSIONS: Nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with Stage I and II melanoma.

Prognostic prediction of the immunohistochemical expression of p16 and p53 in cutaneous melanoma: a comparison of two populations from different geographical regions.

p16INK4a and p53 are tumor-suppressor genes frequently altered in various malignancies, including cutaneous melanoma. The purpose of the study was to establish the prognostic value of immunohistochemical expression of p16INK4a a and p53 in sporadic cutaneous melanoma (CM) in two regions with a high-risk for melanoma in Italy and Ecuador. Immunohistochemical staining of p16 and p53 was performed in samples of primary CM from 82 patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Survival differences between categories of p16 or p53 expression were analyzed using the product-limit procedure (Kaplan-Meier method, log-rank test). Clinical variables (gender, age, tumor location, Clark's level, thickness) were correlated with survival and p16 or p53 expression. p16 nuclear immunoreactivity was observed in 85% of Italian patients compared to 48.7% of Ecuadorians; a small number of cases showed p53 immunoreactivity in both populations. Only nuclear p16 expression exhibited a significant correlation with survival (Italians p=0.001, Ecuadorians p=0.017) but did not appear to correlate with any clinicopathological parameter. No significant difference was observed in survival with regard to p53 expression or cytoplasmic p16. Our results demonstrate that nuclear expression of p16 can be considered a molecular prognostic factor in patients with sporadic CM and indicate its importance as a clinical marker.

Finding of conjunctival melanocytic pigmented lesions within pterygium.

AIMS: Conjunctival pigmented lesions have characteristic clinical and histopathological appearances. Melanocytic pigmented lesions commonly occur in the conjunctiva, although they have not been previously reported in pterygium, a common lesion which originates from conjunctiva. Our aim was to evaluate the possibility of an association between pterygium and conjunctival melanocytic pigmented lesions. METHODS AND RESULTS: A total of 80 samples of pterygium excised from Ecuadorian patients in 2002 were collected. Clinical data were available regarding age, sex, race and place of residence. Histological sections were evaluated for the presence of melanocytic pigmented lesions. Nine cases of conjunctival melanocytic, pigmented lesions within pterygium were found and were classified according to the histopathological criteria previously published for pigmented lesions of the conjunctiva, as naevi and primary acquired melanosis (PAM) with varying degrees of atypia. Five of the nine cases showed primary acquired melanosis without atypia, while two cases had atypia; one case showed features of compound naevus and one lesion was designated as subepithelial naevus. CONCLUSIONS: Our findings suggest that conjunctival melanocytic, pigmented lesions occasionally occur in pterygium. All surgically removed pterygia should undergo careful histopathological examination.

In vivo investigation of hepatic iron overload in rats using T2 maps: quantification at high intensity field (4.7-T).

In vivo quantitation of hepatic iron content is useful in diagnosis and staging of several iron related diseases. We used an experimental model of hepatic iron overload to determine the correlation between iron content and T2 relaxation time in rat liver. Experiments were carried out at 4.7T for high signal-to-noise ratio (SNR) using a spin-echo multiecho sequence with six echoes and minimum echo-time of 5.5 msec. The liver iron content was determined ex vivo by atomic absorption spectrophotometry (AAS). T2 maps were calculated in order to evaluate the space distribution of the iron content. We found good linear correlation between the in vivo liver transversal relaxation rate and the iron content within the range explored (106-4538 microg Fe/g liver wet wt.). T2 maps revealed that the decrease in T2 is not homogeneous through the liver parenchyma. This finding represents a physiological limitation to obtaining better correlation between T2 and iron content.

Intraoperative and percutaneous radiofrequency thermal ablation in the treatment of hepatocellular carcinoma.

AIMS AND BACKGROUND: The aim of the study was to evaluate feasibility, survival rate, complications and length of hospital stay in 47 patients with hepatocellular carcinoma (HCC) treated by radiofrequency thermal ablation (RFTA). Though the treatment of choice for HCC is surgical resection, the strong association of this disease with cirrhosis often rules out this procedure. Many investigations have been conducted in order to identify alternative therapies. Preliminary studies of radiofrequency thermal ablation have shown that the technique is effective and safe, achieving a predictable area of tumor tissue coagulative necrosis and sparing the surrounding cirrhotic parenchyma, without any significant side effects. In addition, this technique, which can be performed percutaneously, allows very short hospital stays. PATIENTS AND METHODS: We report the results of a series of 47 cirrhotic patients with 52 HCC nodules (mean diameter 2.9 cm, range 1-6 cm) treated in our Institute between May 1997 and June 1999 by RFTA using an expandable needle with four hooks at its tip. All patients had hepatic cirrhosis (32 Child A, 13 Child B and two Child C). We treated patients with both unifocal (35 patients) and multifocal HCC (12 patients); 33 patients underwent percutaneous RFTA (54 passes), while in 14 cases RFTA was performed during laparotomy (22 passes). RESULTS: The mean number of passes to achieve complete necrosis was 1.43 in 28 patients with unifocal HCC treated by percutaneous RFTA, 1.7 in 7 patients with unifocal HCC treated by intraoperative RFTA, 2.8 in 5 patients with multifocal HCC treated by percutaneous RFTA and 1.43 in 7 patients with multifocal HCC treated by intraoperative RFTA. No deaths related to the procedure or major complications occurred. Post-treatment dynamic CT was performed in all patients. All patients but one were followed-up for a mean period of 11.8 months (1-25 months). Six patients died during the follow-up (three Child A, two Child B and one Child C. The actuarial survival, computed by the Kaplan-Meier method, was 83% at 24 months. The mean hospital stay was 3.4 days in patients treated by percutaneous RFTA and 11.2 days in those treated by intraoperative RFTA. CONCLUSIONS: In our opinion RFTA is an effective, safe technique capable of achieving good results in the conservative therapy of small HCC. We believe that curative ablation is possible for HCC nodules measuring up to 3 cm in diameter. Further studies of longer duration are necessary.

Role of iron load on fibrogenesis in chronic hepatitis C.

BACKGROUND/AIMS: In chronic viral hepatitis, an enhanced iron load is related to lower response to interferon. Furthermore, iron, through the production of oxygen radicals, may stimulate hepatocyte necrosis and the activation of cells responsible for synthesis and deposition of extracellular matrix. We investigated the relationship between iron load, evaluated by serum assays, and liver fibrogenesis in chronic active viral hepatitis. METHODOLOGY: Serum iron, ferritin, transferrin saturation and serum markers of hepatic fibrogenesis (Laminin and the amino-terminal peptide of procollagen III-NPIIIP-) were assayed in 102 patients (47 females, 55 males, mean age 42.48 years) affected by chronic hepatitis C virus and in 81 healthy controls (47 males, 34 females). In hepatitis C virus patients (studied before alpha-interferon treatment) a semiquantitative score for portal inflammation, necrosis and fibrosis was applied to liver biopsy. RESULTS: Serum indices of iron load were higher in hepatitis C virus patients than in controls, and were higher in cirrhotic than in chronic hepatitis cases. Ferritin and serum iron were positively correlated with NPIIIP and laminin; moreover cases with ferritin levels over the normal limit for sex and age had higher levels of NPIIIP and laminin than cases with normal or poor iron status. CONCLUSIONS: Our data suggest that even a mild increase of iron load stimulates hepatic fibrogenesis, probably adding oxygen free radical injury to the damage of viral infection.

Hepatocellular carcinoma: correlation between gadobenate dimeglumine-enhanced MRI and pathologic findings.

RATIONALE AND OBJECTIVES: To correlate the appearance of hepatocellular carcinoma on delayed (60 minutes) postcontrast T1-weighted gradient echo images with the mode of action of gadobenate dimeglumine (Gd-BOPTA) and the anatomic and pathologic characteristics of the lesions. METHODS: A total of 34 patients with hepatocellular carcinoma and varying degrees of diffuse liver disease were studied. T2-weighted spin echo and T1-weighted spin echo and gradient echo images were acquired before and 60 minutes after the intravenous administration of 0.1 mmol/kg Gd-BOPTA. Qualitative and quantitative evaluations of the images were performed and correlated with histologic findings. The quantitative evaluation, performed on T1-weighted gradient echo images, looked at the percentage increase of liver enhancement after Gd-BOPTA administration, the lesion-to-liver contrast/noise (C/N) ratio before and after Gd-BOPTA administration, and the C/N variation after Gd-BOPTA administration. Qualitative assessment considered the morphologic features of the lesions as well as the visual variation of contrast before and after Gd-BOPTA administration. Finally, a histologic evaluation was made of the degree of differentiation of the lesions and of the presence of fatty metaplasia, necrosis, bile, or intratumoral peliosis. RESULTS: Among the parameters affecting lesion identification were the extent of liver function, degree of vascularization, residual functionality of the tumor cells, and characteristics of the neoplastic tissue. Positive correlations (Spearman coefficients = 0.359 and 0.393, respectively) were observed precontrast between the degree of liver failure and the amount of contrast noise, and postcontrast between the amount of intralesional fatty metaplasia and the extent to which lesion conspicuity worsened after Gd-BOPTA administration. An inverse correlation (Spearman coefficient = -0.330) was observed between the degree of lesion differentiation and the visible appearance after Gd-BOPTA administration, with well-differentiated lesions tending toward worsened conspicuity postcontrast. A statistically significant difference (P = 0.001) was observed in the mean precontrast C/N ratio for lesions later showing unchanged conspicuity and worse conspicuity on postcontrast images, respectively. Marked variation (P = 0.019) was also observed between Child A and B cirrhotic patients for the degree of hepatic enhancement on postcontrast images. CONCLUSIONS: The results suggest that liver parenchyma signal intensity is influenced by the extent to which liver function is compromised, that residual hepatocytic functionality permits Gd-BOPTA uptake by certain lesions and that this uptake might subsequently impair the observed C/N ratio on delayed images, and that the worsening of lesion conspicuity on postcontrast images is influenced also by high quantities of intralesional fatty metaplasia.

Panniculitis induced by collagen and plexiglas microsphere injections used for aesthetic treatment.

The authors report an unusual case characterised by the prompt appearance of panniculitis after injections of collagen and plexiglas microsphere for aesthetic aim and review the literature about aesthetic treatments and rheumatic disorders.

Hepatic angiomyolipoma: a clinicopathologic study of 30 cases and delineation of unusual morphologic variants.

Hepatic angiomyolipoma (AML) is frequently misdiagnosed. HMB-45 is a promising immunomarker for this tumor that leads to recognition of some AMLs with unusual morphology. The purpose of this collaborative study is to better define the morphologic variations of AML. Thirty AMLs were examined, including four biopsy specimens and two fine-needle aspirates. The diagnosis was confirmed by the presence of HMB-45-positive myoid cells. Almost half the cases were originally misdiagnosed as carcinomas or sarcomas. There was marked female predominance (25:5), and the mean age was 48.7 years (range 29-68). Three patients (10%) had evidence of tuberous sclerosis and all had renal AML. According to the line of differentiation and predominance of tissue components, the tumors was subcategorized into mixed, lipomatous (> or = 70% fat), myomatous (< or = 10% fat), and angiomatous type. The mixed type was the most common (11 resected cases), comprising sheets of epithelioid muscle cells admixed with islands of adipocytes, abnormal vessels, and frequently, hematopoietic cells. Six tumors (including three from biopsy specimens) were heavily fatty and showed predominantly adipocytes with epithelioid and short spindle myoid cells webbed between fat cells. Of 10 myomatous AMLs, five tumors showed a pure sinusoidal trabecular pattern and comprised mainly epithelioid cells. Typically, mature adipocytes were absent or scanty, but fat was seen as fine droplets within cytoplasm or as occasional large globules in sinusoids. Pelioid and inflammatory pseudotumor-like patterns were identified focally. Regarding cellular features of the myoid cells, most of the epithelioid cells were either eosinophilic or clear with spiderweb cell morphology. Three AMLs showed an almost purely oncocytic appearance with scanty fat. Large pleomorphic epithelioid cells existed as small foci. Spindle cells arranged in long fascicles were uncommon. D-PAS-positive globules were common around pelioid areas. Brown pigments with staining characteristics of hemosiderin and/or melanin were noted. In conclusion, we propose HMB-45-positive myoid cells as the defining criterion of hepatic AML, which is a tumor capable of dual myomatous and lipomatous differentiation and melanogenesis. Because of its protean morphologic appearance, recognition of the various variant patterns and cell types is important for a correct diagnosis, assisted by immunohistochemical confirmation with HMB-45. Trabecular and oncocytic cell tumors appear to stand out as distinctive subtypes.

Prompt hepatitis C virus suppression following hepatitis B virus superinfection in chronic untreated hepatitis C.

The natural course of chronic hepatitis C virus infection after hepatitis B virus superinfection is not clear since it is difficult to determine the chronology of the double infections. We report on a case of de novo hepatitis B virus infection in the course of chronic untreated hepatitis C, in which the time of hepatitis B virus infection is actually known. The patient eliminated HCV-RNA, both from serum and from liver tissue, soon after the clinical onset of the acute hepatitis B. Liver histology featured hepatitis with severe portal inflammation and high-grade periportal and intralobular necro-inflammatory lesions. This observation demonstrates that hepatitis C virus replication can be promptly and spontaneously suppressed by acute hepatitis B virus superinfection.

Serum laminin and type III procollagen in chronic hepatitis C. Diagnostic value in the assessment of disease activity and fibrosis.

Laminin P1 (pepsin-resistant fragment of laminin) and aminoterminal peptide of type III procollagen are measurable in serum and are now considered useful serum markers of fibrogenesis and inflammation in chronic liver diseases. However, very few studies thus far have focused on assessing the diagnostic value of these markers in detecting fibrosis and necro-inflammatory activity in chronically diseased liver. The aim of the present study was therefore to investigate the correlations of laminin and type III procollagen with liver histology and to compare their diagnostic value in detecting the degree of liver fibrosis and necro-inflammatory activity in a homogeneous group of 99 patients suffering from chronic hepatitis C, and lacking other factors which can directly affect the serum levels of the two markers. Both these serum markers were measured by radioimmunoassay, employing commercially available kits. The three main aspects of liver pathology, i.e. portal-periportal activity, lobular activity and fibrosis, were histologically evaluated and semiquantitatively expressed by numerical scores. The results of this study show that laminin and type III procollagen were both positively correlated with the histological scores for portal-periportal activity and with those for fibrosis, whereas no significant correlation was observed between each of the two serum markers and the histological scores for lobular activity. The sensitivity and specificity of laminin and type III procollagen in detecting histological aspects of fibrosis and disease activity in liver, computed at various cut-off levels, showed overlapping trends for the two markers; however, the diagnostic value was in general rather low, whatever the cut-off considered. We therefore conclude that the 'static' measurement of both serum laminin and type III procollagen is of limited value for individual diagnosis of liver damage.