An unusual presentation of primary cutaneous follicle center lymphoma.

Primary cutaneous follicle center lymphoma (PCFCL) is a rare low-grade cutaneous B-cell lymphoma. Clinically, PCFCL is usually an erythematous subcutaneous nodule or an infiltrated plaque. The dermoscopy is non-specific and it is characterized by polymorphous vascular pattern, arborizing vessels over a salmon-colored background and white areas. We reported a case of a 36-year-old woman presented with a rapidly growing, flashed-color, exophytic, soft consistency nodule on her scalp. Dermoscopy showed a diffuse structureless, skin-color area associated with a rare arborizing vascular pattern and brown circles. We reported a peculiar clinical and dermoscopic variant. This clinical presentation of PCFCL is unusual and represents a pitfall in the early clinical diagnosis. Histopathology is mandatory for a correct diagnosis.

Use of tocilizumab in amyloid a nephropathy associated with Sweet syndrome: a case report and literature review.

Amyloid A nephropathy is a possible complication of chronic inflammatory disease. Proteinuria and kidney failure are the main features of the disease. Tocilizumab (TCZ), an IL6-R antibody approved for rheumatoid arthritis, is a promising choice for histologically demonstrated nephropathy. We describe a case of kidney amyloid associated with Sweet syndrome treated with TCZ. The patient was affected by Sweet syndrome associated with proteinuria. Kidney biopsy showed amyloid deposits. During the follow-up, cutaneous and renal findings were refractory to many immunosuppressive regimen (cyclophosphamide, leflunomide, interferon and steroid). After few years, the patient developed rapidly progressive nephropathy associated with nephrotic syndrome (proteinuria up to 6 g/die). A second kidney biopsy was performed and it showed worsening of amyloid nephropathy. Thus, TCZ was administrated (8 mg/kg once a month) and it stabilized kidney function and induced partial remission of the nephrotic syndrome in the following 2 years.

Proteinuria is a late-onset adverse event in patients treated with cabozantinib.

PURPOSE: The use of tyrosine kinase inhibitors (TKIs) in thyroid cancer patients is often limited by toxicities. Some have a long-term onset and potentially could impact patients' survival. Among them, there is the nephrotoxicity, mainly represented by proteinuria. The aim of the study was to evaluate the prevalence of proteinuria in medullary thyroid cancer patients treated with cabozantinib, to examine whether it could be a marker for treatment monitoring and to evaluate histological kidney alterations. METHODS: We collected data of 31 medullary thyroid cancer patients enrolled in the EXAM trial. Proteinuria was defined and evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events. In two symptomatic cases with high-grade proteinuria, a kidney biopsy was performed. RESULTS: Proteinuria was observed in 4/18 patients (22.2%) and occurred after a mean period of 38 months (median: 35.5 months). It was significantly associated with previous chemotherapy (p = 0.005) and/or treatment with other TKIs (p = 0.04), a prolonged use of cabozantinib (p = 0.0004), and a better radiological response at the end of follow-up (p = 0.002). The kidney biopsy showed pathognomonic features of thrombotic microangiopathy in both cases and a focal amyloid deposit in one. CONCLUSION: Proteinuria is a quite frequent adverse event during cabozantinib treatment. It is relatively well manageable with the early detection and correction of risk factors, the temporary discontinuation of cabozantinib and/or its dose reduction, and the use of anti-proteinuric and renoprotective drugs in patient with hypertension. The histological findings confirmed some typical features of the anti-VEGF inhibition injury, already described for other TKIs.

[Poorly differentiated breast carcinoma with an abundant myoepithelial component: morphologic and immunohistochemical features and mammaglobin gene expression ]. / Carcinoma scarsamente differenziato a ricca componente mioepiteliale della mammella: aspetti morfologici, immunoistochimici ed espressione del gene mammaglobin.

In this report, we describe a case of poorly differentiate myoepithelial cell rich carcinoma in with morphological findings of large poligonal nests with festoon-like pattern sometimes showing central necrosis, reminiscent of a comedo-like pattern and numerous mitoses. Immunohistochemical staining shows positive reaction for cytokeratin AE/1, CAM 5.2, 34 beta E12, vimentin, smooth muscle actin, EMA, S100 protein and oncogene cERB.b2 and negative for estrogen, progesterone, GFAP and chromogranin. Moreover, this carcinoma show the expression of the mammaglobin mRNA, a highly specific marker of breast epithelial cells that it is not expressed in all breast carcinoma.

Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas.

Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2 +/- 28.5 vs 29.3 +/- 19.7; p < 0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p < 0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p = 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

Angiogenesis in human normal and pathologic adrenal cortex.

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

Apoptosis control and proliferation marker in human normal and neoplastic adrenocortical tissues.

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-1, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1+/-1.9%) and in carcinomas (14.9+/-5.6%) than in normals (2.9+/-0.9%) and aldosterone-producing adenomas (5.3+/-1.3%) since four specimens of the non-functioning adenomas-group (30.7%) and six of the carcinomas-group (37.5%) showed over 10% positivity (cut-off for normal values, set at 90th percentile of our controls). MIB-1 positivity was 0.50+/-0.36% in normals, 0.54+/-0.08% in non-functioning adenomas and 0.54+/-0.08% in aldosterone-producing adenomas. MIB-1 was expressed in all carcinomas with values (13.7+/-3.1%) significantly (P<0.0006) higher than in the other groups. In conclusion, the present data indicate that the apoptosis control and proliferation activity evaluated by the p53 and MIB-1 proteins are impaired in adrenal carcinomas but preserved in adenomas, independently of their functional status. Therefore, these immunohistochemical markers, overexpressed in carcinomas only, may be useful in the diagnosis of malignancy in adrenocortical tumours. Whether Bcl-2 positivity found in some carcinomas and non-functioning adenomas may constitute, in the latter, a negative prognostic marker is still unknown.

[Hashimoto's thyroiditis in "struma ovarii". Case report and review of the literature]. / Tiroidite di Hashimoto in "struma ovarii" puro. Caso clinico e revisione della letteratura.

Struma ovarii, a teratoma in which thyroid tissue is the predominant or sole component account for 2.7% of all ovarian tumors. Pathogenesis is unclear. In addition to symptoms and signs caused by the presence of a mass, struma may be associated with a number of unusual clinical manifestations. Ascitis occurs in approximately one third of the cases, Meigs' syndrome occasionally and hyperthyroidism in only about 5% of cases. Thyroiditis is an occasional finding and Hashimotos' thyroiditis is rare in struma ovarii. The struma may resemble normal thyroid tissue, a thyroid adenoma or thyroid carcinoma. The treatment is surgical and the outcome generally favorable. This paper reports the first clinical case of a patient with Hashimoto's thyroiditis in a pure struma ovarii associated with positive specific antithyroid antibodies in the absence of symptoms and signs due to thyroid disease.

[Adenoid cystic carcinoma of the prostate. Clinical case]. / Carcinoma adenoido-cistico della prostata. Caso clinico.

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

Bio-morphological events in the development of the human female mammary gland from fetal age to puberty.

Bio-morphological understanding of the developing human mammary glands may clarify some aspects of breast pathology, including cancer. In particular, some epidemiological data suggests that during fetal growth an altered intrauterine hormonal status, especially a change in estrogen status, could predispose to carcinogenesis. In an attempt to achieve new information on early breast growth, a series of developing human breasts have been analyzed, namely: 4 fetal breasts (28-32 weeks of gestational age), 7 infant breasts (7 h to 2 years) and 1 puberal breast (12 years). In addition to the morphological features, we studied the immunohistochemical expression of some markers involved in morphogenesis, such as MIB-1 for cell proliferation, bcl-2 for apoptosis control, CD34 for vasculogenesis, estrogen (ER) and progesterone (PR) receptors for hormonal profile, and smooth-muscle actin for myoepithelial differentiation. The results were as follows: (a) lobules, absent between 28 weeks and 2 days, were well evident at 2 years of age and at puberty; (b) myoepithelial cells appeared from 28 weeks onward and persisted later with no modification in quantity and distribution; (c) epithelial cell proliferation was constantly low; (d) in all breasts inner epithelial cells showed diffuse bcl-2 positivity, while basal myoepithelial-like cells were generally negative; (e) all breasts were well vascularized with two different patterns: periductal vascularization (PDV) and interductal vascularization (IDV), IDV being always present, whereas PDV was found only in infant breasts; (f) ER and PR were almost absent in fetal and infant breasts, while their expression was high in the epithelial cells of the puberal breast; (g) stromal cells had no hormonal receptors and were heterogeneous for proliferation and bcl-2 expression. Interestingly, two fetal breasts showed high proliferation and high ER expression, respectively, in their epithelial compartment. This could be the expression of an altered hormonal environment in utero, representing a basis for possible subsequent cancer initiation.

Cutaneous spreading of parathyroid carcinoma after fine needle aspiration cytology.

BACKGROUND: Ultrasound-guided fine needle aspiration cytology (FNAC) of suspect parathyroid adenomas is sometimes used for the diagnosis of primary hyperparathyroidism (PHPT). FNAC complications are rare or mild. We describe the first case in literature of cutaneous spread of parathyroid carcinoma after FNAC. CASE: A woman underwent a neck ultrasound which revealed a solid hypoechogenic nodule of 1.5 cm at the level of the inferior pole of the right thyroid. In the same time a FNAC of the nodule was performed. Cytology showed no atypical cells. Successively PHPT was diagnosed and a few weeks later the patient had a subcutaneous lump in the same area of FNAC. The patient underwent surgery and histology of the specimen showed a differentiated parathyroid carcinoma. The postoperative course was regular and calcium and parathormone resulted normal. CONCLUSION: The use of FNAC should be carefully assessed in the presence of suspect parathyroid carcinoma, because this could cause a possible diffusion of a parathyroid carcinoma along the needle tract.

Diagnosis of adrenal adenoma: value of central spot of high-intensity hyperintense rim sign and homogeneous isointensity to liver on gadolinium-enhanced fat-suppressed spin-echo MR images.

Eighty-nine patients with 108 adrenal masses, either adenomas (n = 88) or malignant lesions (n = 20), underwent magnetic resonance imaging (MRI) of the abdomen at 0.5 T for the purpose of determining whether adrenal adenomas could be differentiated from malignant lesions on gadolinium-enhanced fat-suppressed T1-weighted spin-echo (SE) images (Gd-E FS T1WI) and on T2-weighted SE images. The imaging protocol included conventional unenhanced SE T1- and T2-weighted sequences and Gd-E FS T1WI. Three observers independently evaluated signal intensity on unenhanced and enhanced images and also the presence of structures of high signal intensity in the outer margin [hyperintense rim sign (HRS)] or in the center [hyperintense central spot (HCS)] of the adrenal masses. Forty-one (46.5%) of 88 adenomas were homogeneously isointense to liver in unenhanced and enhanced T1-weighted sequences and in T2WI. HCS and HRS were observed in 33/88 (37.5%) and 15/88 (17%) adenomas, respectively, on Gd-E FS T1WI; in contrast, these signs were never revealed in any case of malignant lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in classifying lesions as suggestive of adenoma were 93%, 90%, 98%, 75%, and 93%, respectively. Visual evaluation of details of tumor structures on Gd-E FS T1WI allows good characterization of adrenal masses. HCS, HRS, and homogeneous isointensity to liver are characteristic signs of adrenal adenomas.

Benign ovarian fibroma associated with free peritoneal fluid and elevated serum CA 125 levels.

This paper reports the clinical case of a patient with ovarian neoplasia, ascites effusion, and elevated serum CA 125 levels (411 U/ml). This condition simulated a malignant pathology on the grounds of preoperative diagnostic examinations. Surgical investigation diagnosed an ovarian fibroma and ascites. Ascites was resolved rapidly and the serum CA 125 levels decreased after surgical neoplasia removal. An ovarian neoplasia associated with ascites effusion and elevated serum CA 125 levels (also in the presence of suspect ecographic and tomographic features) do not necessarily imply a malignant neoplasia.

Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues.

An altered control of the mechanisms involved in cell proliferation and programmed cell death (apoptosis) might play an important role in parathyroid tumorigenesis. We evaluated by immunohistochemistry the expression of bcl-2 and p53 proteins, as markers of apoptosis control, and MIB-1, as marker of cell proliferation, in a series of normal and neoplastic parathyroid tissues. The specimens were 33 normal parathyroids, 43 parathyroid adenomas and 3 parathyroid carcinomas. Results were scored as positive when more than 1% of cells were stained for MIB-1 and p53, and more than 10% for bcl-2. All normal parathyroids showed numerous bcl-2 positive cells (> or = 80%), low proliferation rate (MIB-1) and no p53 protein expression. Twenty-four (55%) adenomas were bcl-2 positive; in 16 of these the number of positive cells was high (> 50%) and immunoreactivity was diffusely distributed within the adenoma; 8 cases showed a zonal staining pattern, in which groups of stained cells were surrounded by negative cells. Nineteen adenomas (45%) and all carcinomas were bcl-2 negative. A high proliferative rate (MIB-1) was found in all carcinomas and 4 adenomas (9%); all MIB-1 positive adenomas were bcl-2 negative. p53 was negative in all specimens. No significant differences in serum calcium and intact PTH levels nor in tumor size were found between bcl-2 negative and bcl-2-positive and MIB-1-positive and MIB-1-negative adenomas. An inverse, but not statistically significant (p = 0.06) correlation was observed between the percentage of bcl-2 positive cells and serum calcium level in parathyroid adenomas. In conclusion, parathyroid adenomas are a heterogeneous group of lesions in which the pattern of bcl-2 and MIB-1 protein expression ranges between that of normal parathyroid (bcl-2 positivity and MIB-1 negativity) and that of parathyroid carcinoma (bcl-2 negativity and MIB-1 positivity). The question of whether the finding of the MIB-1 positive-bcl-2 negative phenotype identifies a subgroup of clinically more aggressive adenomas remains to be established.