Exploring the mesenteric lymphatic apparatus: A morphological and immunohistochemical investigation with clinical correlations.

Modern immunohistochemical techniques allow a detailed study of the lymphatic system in many organs and areas of the body. We performed an in-depth study on lymphatic vessels of the ileal and colonic mesenteries, together with the greater omentum where they appear particularly numerous and mainly represented by capillaries interconnected among themselves and with lymph nodes. The capillary wall consists of a fine single sheath of endothelial cells wrapped around by a subtle collagen membrane and deprived of valves. The progression of lymph flow is promoted by external forces acting on the capillary walls. Only at the mesenteric roots can pre- and post-lymph nodal collector vessels be observed. Our observations help to explain different patho-physiological correlations and the possible presence of skip lymph node metastases.

Mitochondrial DNA content: A new biomarker for sudden intrauterine unexplained death syndrome (SIUDS).

In literature there are no data related to mitochondrial DNA (mtDNA) content in sudden intrauterine unexplained death syndrome (SIUDS). To test the hypothesis that a quantitative excess of mtDNA could play a role in the pathogenesis of SIUDS, mtDNA content was measured in cerebral cortex of 9 SIUDS and in 7 controls. The median (interquartile range) mtDNA in SIUDS and controls was 14,000 (8600-33,500), 3400 (0-8500) copies per nuclear DNA, respectively (p=0.007). If mitochondria are involved in SIUDS, then higher mitochondrial DNA content may be a biomarker of this syndrome.

SAMPUS, MELTUMP and THIMUMP - Diagnostic Categories Characterized by Uncertain Biological Behavior.

In the dermatopathological practice, there is a group of atypical melanocytic lesions with borderline histological features between benign simulants and malignant melanoma (MM), due to conflicting diagnostic criteria and inter-observer disagreement. In these cases, the dermatopathologist is authorized to seek consult with an established expert in the field, but even the most experienced specialist may not be sure about the correct diagnosis and the subsequent biological behavior. There is general consensus among qualified dermatopathologists that can be helpful to insert these ambiguous cases into two diagnostic categories: SAMPUS (Superficial Atypical Melanocytic Proliferations of Unknown Significance) and MELTUMP (MELanocytic Tumors of Uncertain Malignant Potential). According to the conception of MM progression through two phases, the radial growth phase and the vertical growth phase, it is possible to identify a novel subtype of thin melanoma (THIM) with uncertain metastatic potential, due to the presence of extensive regression ( 75% of the lesion volume), which we here define with the acronym THIMUMP (THIn Melanoma of Uncertain Metastatic Potential) for the first time in literature.Key words: malignant melanoma - thin melanoma - histology.

Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience.

Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.

New advances on placental hydrops and related villous lymphatics.

Fetoplacental hydrops is the final stage of several pathological conditions in which the placenta and umbilical cord become edematous and the fetus develops an anasarcatic state characterized by an excessive accumulation of extravascular fluids in at least two serous cavities of the body. It is a common histological finding of stillbirth, characterized by the appearance of markedly edematous villi, suggesting an increased interstitial fluid accumulation. The recent improved knowledge of lymphangiogenesis and the availability of monoclonal antibodies selectively labeling lymphatic endothelium lead to the hypothesis that villous edema is essentially a lymphedema from defective lymphatic function following inadequate villous blood circulation. Lymphedema is a morphologic phenotype found by our research group in a 24-case series of stillbirths from different morbid conditions such as chromosomal aberrations, congenital malformations, inherited hemoglobinopathies, and prolonged perinatal severe anoxia. Unlike long-lived organs, the placenta is devoid of innervation by the autonomic nervous system; therefore, the vascular tone regulation and the peripheral perfusion are modulated by the expression of the angiotensin converting enzyme (ACE) in the vascular endothelia. This finding may suggest to the clinician to search for a more suitable therapy in case of mother's hypertension during pregnancy.

Acquired immunodeficiency similar to Gulf War illness in a dead former serviceman.

A 38-year-old non-commissioned officer was certified unfit for military duty several months before his death. The forensic autopsy revealed a severe bone marrow aplasia and a pulmonary angioinvasive aspergillosis. Moreover, the presence of inorganic foreign particles in the pulmonary macrophages and intestinal endothelia was observed. The microanalysis implemented on these last selected specimens revealed the presence of silica particles microimpregnated by lanthanides and steel. The patient's acquired immunodeficiency appears comparable with that of Iraqi civilians suffering from Gulf War illness. This is the first report in the literature of the presence of intestinal endothelia engulfed by foreign war particulates; the silica particles may have entered the intestinal endothelia via the blood stream or by ingestion of impregnated fruit and vegetable foodstuffs. This finding provides new perspectives in the assessment of war-associated diseases and includes electron probe microanalysis among the new techniques of military and forensic medicine.

"Pure" primary large cell neuroendocrine carcinoma of the urinary bladder: case report, literature review and diagnostic criteria.

INTRODUCTION: Large cell neuroendocrine carcinoma (LCNC) is defined in the urinary bladder, as in other sites, as a high-grade neoplasm exhibiting neuroendocrine features at the H&E level, high mitotic activity and evidence of neuroendocrine differentiation by immunohistochemistry. We report a case of pure bladder LCNC with review of the literature. METHODS: A 68-year-old male presented with gross haematuria of two weeks' duration in October 2011. Transurethral resection and subsequently radical cystoprostatectomy (CP) with bilateral lymphadenectomy (L) were performed in December 2012. RESULTS: Urinary cytology identified malignant cells. Histologically, the tumour showed organoid nesting, trabecular growth, rosettes and perilobular palisading patterns, suggesting neuroendocrine differentiation. Immunohistochemical staining showed intense positivity for CD56. DISCUSSION: We examined all published pure bladder LCNC (12 cases) excluding mixed neoplasms. Small cell carcinoma of the urinary bladder pure LCNC of the bladder is a very aggressive malignancy, unresponsive to therapy, presents in an advanced stage and has a propensity for early metastasis. Prior to the advent of immunohistochemistry, such cases would most likely have been categorised as poorly differentiated, high-grade urothelial carcinomas.

Giant benign solitary fibrous tumour of the pleura (> 15 cm): role of radiological pathological correlations in management. Report of 3 cases and review of the literature.

OBJECTIVES: Solitary fibrous tumour pleura (SFTP) is a localized tumour arising from the submesothelial areolar mesenchyme. In the present study, we defined "giant" lesions with diameter greater than 15 cm. We have studied the role of radiological-histological correlations of three cases in the management of the disease with review of the literature. METHODS: We conducted a retrospective review of the clinical records of three patients who had undergone surgical resection for giant benignant SFTP between 2007 and 2011. RESULTS: Three symptomatic patients (all woman, mean age 80 years) with a giant benign SFTP (mean diameter 19.3 cm and mean weight 1290 gm) underwent surgery with full excision of the tumour. All tumours showed histological features of benignancy and intense immunopositivity for CD34. CONCLUSIONS: The integration of CT and pathological findings is essential in the optimal management of giant benign SFTP. Chest radiograph and CT cannot differentiate between benign and malignant giant SFTP. Surgical resection is necessary to determine the nature of tumour. The immunohistochemical staining pattern assists in differentiating SFTPs from other spindle cell neoplasms of the pleura including diffuse malignant mesothelioma. The choice of surgical approach is determined by the location of the tumour and by spatial relations in the imaging study rather than by the radiologist's impressions. Recurrence after complete resection is possible in giant benign SFTP, as a consequence of incomplete excision. Long-term follow-up is highly recommended because of the possibility of late recurrence. Due to rarity of these tumours, further studies and multicentre trials are needed to confirm these preliminary findings.

Theory and practical application of superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) and melanocytic tumours of uncertain malignant potential (MELTUMP) terminology: experience with second opinion consultation.

INTRODUCTION: The term superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) is used to resolve discordance in diagnosis of "thin" melanocytic lesions. Melanocytic tumours of uncertain malignant potential (MELTUMP) is the descriptive term for an ill-defined group of dermal melanocytic tumours that exhibit features indicative of possible malignancy. We report our experience of collaboration with two leading international consultant pathologists in the diagnosis of melanoma in order to facilitate the practical application of the term SAMPUS and MELTUMP. METHODS: Twenty-seven cases of melanocytic lesions with interpretative problems were sent for consultation to Expert #1 (15 cases) and Expert #2 (12 cases). RESULTS: Two cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #1; three cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #2. Diagnosis was performed with H&E and molecular studies were not performed. DISCUSSION: Both experts included MELTUMP or SAMPUS atypical, ambiguous melanocytic lesions and melanomas. The diagnosis of SAMPUS and MELTUMP by consultant pathologists reflects the difficulty of classification with accuracy lesions that showed histological features of various atypical tumours or malignant melanoma. In these cases, biological potential may be established with molecular studies.

Ovarian fibromatous tumours of uncertain biological potential: study of three cases.

BACKGROUND: The classification of ovarian fibromatous tumours with high mitotic activity is controversial. CASES REPORT: The first case was an 18 x 17 x 10 cm left ovarian fibromatous tumour with 17 mitoses/10 HPF detected in a 44-year-old woman. The second case consisted of a 4 x 2.5 x 2 and a 2.5 x 2.5 x 2 cm fibrmatous tumours found, respectively, in the left and right ovaries of a 67-year-old woman. The mitotic count varied from 4 to 6/10 HPF. CONCLUSIONS: Prat & Scully reported that mitotic activity was the most important factor in diagnosing fibrosarcomas, and that cellular pleomorphism was not reliable. Irving et al. suggested that cellular fibromatous neoplasms with bland nuclear features and mitotic count of > or = 4 MFs/10 HPFs should be considered mitotically-active cellular fibromas rather than fibrosarcomas. We propose the term 'fibromatous tumours of uncertain biological potential' when an average mitotic count of 4 or more per 10 HPFs are found and nuclear atypia and necrosis are absent.

Sebaceous carcinoma of the vulva: critical approach to grading and review of the literature.

BACKGROUND: Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma (SC) is an uncommon neoplasm. METHODS: We report a case of SC of the vulva in a 51 year-old woman. RESULTS: The patient presented a 6-month history of an asymptomatic 2.5 x 1.5 cm exophytic tumour localized on the left labium majora. Tumorectomy was performed. Histologically, the lesion had an irregular lobular growth pattern composed of lobules or sheets of malignant cells separated by fibrovascular stroma. There was a mixture of sebaceous-type differentiation, small ducts and areas showing basaloid or squamous features. Centrally-located tumour cells showed moderate EMA immunoreactivity, especially enhancing cytoplasmic "bubbliness". Tumour cells were immunoreactive for CAM 5.2. The immunoreactivity for intranuclear p53 staining was > 10%. Southern blot hybridization and PCR studies did not detect HPV DNA. Hemivulvectomy was performed. After 18 months of follow-up, the patient has no evidence of recurrence, metastases or other malignant tumours. CONCLUSIONS: The grading of cutaneous SC proposed by Rutten et al. (World Health Organization Classification of Skin Tumours) and Patterson & Wick (Nonmelanocytic Tumours of the Skin. Armed Forces Institute of Pathology) is based on patterns of tumour growth rather than cytological features. Such grading of skin SC, including vulvar SC, should not be used since its prognostic value has not been sufficiently documented. As the number of reported vulvar SCs is very limited, their natural history is unknown and the optimal treatment has not been established. The follow-up of 7 reported cases supports the general opinion that the tumour may be aggressive. SC groin node metastases carry a devastating prognosis, and unrecognized disease in the inguinofemoral lymph nodes is nearly always fatal. The use of sentinel lymph nodes (SLN) has evolved as an effective surgical technique for identifying early subclinical regional nodal involvement for many solid tumours throughout the body for staging disease; this is because extra-ocular SCs cause widespread metastatic disease. In our opinion, SLN should be used in conjunction with wide local excision of the primary tumour to investigate regional subclinical metastases. In the presence of a positive sentinel node, early lymphadenectomy with or without radiotherapy could be used to reduce tumour-related morbidity and mortality. The histopathologic differential diagnosis of SC is wide-ranging, including virtually all other malignant clear cell tumours of the skin. The proliferative pattern, immunostaining and cytologic features permit exclusion of neoplasms that mimic SC, but a diagnosis of SC should be rendered only if the overall attributes of the lesion are appropriate for such a interpretation.

Oncocytic carcinoma of the parotid gland: case report and review of the literature.

OBJECTIVES: To date 70 cases of oncocytic carcinomas (OCs) have been described in 55 reports. We describe an OC of the parotid gland in a 56-year-old man with simultaneous breast cancer. METHODS: In June 2006, a 56-year-old man was referred to the Otorhinolaryngology Division for a painless right preauricolar mass. The facial nerve was functionally normal. Total parotidectomy with facial nerve preservation was performed. In January 2007, the patient was referred to the Surgical Division for a left mammary nodule. Total mastectomy with axillary lymphoadenectomy was performed. RESULTS: The mass of the parotid gland measured 3.5 x 3 cm. Histology showed sheets, islands and nests composed of large, round to polyhedral cells with fine, granular, eosinophilic cytoplasm and round vesicular nuclei, with prominent nucleoli. The tumour cells were positive for immunohistochemical staining with antimitochondria antibodies. Histological examination of the mammary tumour showed invasive ductal carcinoma Grade III (Nottingham Histologic Score) with metastasis in 12 axillary lymph nodes. Chemotherapy was performed. At present, the patient is free of recurrences or metastases. CONCLUSIONS: Histologically, there is a spectrum of malignant parotid gland neoplasms that have prominent eosinophilic granular cytoplasm due to increased number of mitochondria. OCs have cytoplasm packed with mitochondria, while the term "oncocytoid" should be employed for tumours that have abundant eosinophilic granular cytoplasm, but ultrastructurally do not possess marked mitochondrial hyperplasia. All reported cases of OC should be defined "oncocytic-like carcinoma" when only haematoxylin and eosin staining is performed.

Squamous cell carcinoma arising in epidermal and human papillomavirus associated cysts: report of three cases.

OBJECTIVES: The clinical-pathological features of squamous cell carcinoma (SCC) arising in cutaneous cysts has been studied. METHODS: We report two cases of SCC arising in epidermal cyst (EC) and one case in human papilloma virus associated cyst (HPAC). RESULTS: In the first EC case, a 88-year-old man presented a cystic right zigomatic mass. Histopathology revealed a cyst lined by stratified squamous epithelium in continuity with invasive keratinizing SCC. In the second EC case, a 96-year-old man presented with a 1.5 x 1 cm nodular lesion localized at the helix of the right ear. Histopathology showed the typical cystic wall of an EC with transition to invasive keratinizing SCC. Finally, a 86 year-old woman presented with a perineal cystic nodule 1.5 cm in diameter. The wall showed varying degrees of papillomatosis, hypergranulosis, parakeratosis with dysplastic and koilocytic changes. Areas of in situ and invasive SCC were found. Human papillomavirus (HPV) 16 was detected. CONCLUSIONS: SCC arising in an EC may be diagnosed only with the support of an accurate histopathological documentation in order to exclude mimics. Regarding HPAC, the site, the malignant transformation and the finding of HPV 16 type, may be considered features of an extraordinary rare case.