Obliterative foam-cell arteriopathy. A unifying concept embracing several entities previously described as radiation, decidual, transplant, and intratumoral-associated arteriopathy.

This review article aimed to postulate the existence of a specific arterial injury having as its histological hallmark a collection of macrophages loaded with lipids in the intima of small-sized and medium-sized arteries causing narrowing or complete obstruction. The proposal is made that a series of previously described entities, such as ionizing radiation arteriopathy, acute atherosis (foam-cell decidual arteriopathy), transplant chronic arteriopathy of solid organ allografts, and intratumoral-associated foam-cell arteriopathy constitute different manifestations of the same basic morphological process identified as obliterative foam-cell arteriopathy (OFCA). OFCA is a local (single-organ) lesion in the aforementioned diverse processes with variable etiopathogenesis but converges in a single morphological marker. This arteriopathy is essentially an intimal disease. The processes in which the OFCA appears are known under a variety of names partly dependent on the location of the lesion. The basic unifying mechanism of the different entities is endothelial activation and dysfunction (local arterial endotheliopathy), preferably in small-sized or medium-sized arteries (100 to 500 µm in external diameter).

Protooncogene MYC drives human melanocyte melanogenesis and senescence.

In spite of extensive research and advances on the molecular biology of melanoma, the process of melanocytic differentiation or its relationship with proliferation is poorly understood. The role of proto-oncogenes in normal melanocyte biology is also intriguing. Proto-oncogene MYC is overexpressed in 40% of melanomas. It has been suggested that MYC can mediate senescence bypass in malignant melanocytes, an important event in melanoma development, likely in cooperation with other oncogenic pathways. However, despite the apparent importance of MYC in melanoma, its functions in normal melanocytes are unknown. We have overexpressed MYC in freshly isolated human primary melanocytes and studied the effects on melanocytic proliferation and differentiation. MYC promoted a transient activation of melanocytes including cell cycle entry, DNA damage and cell migration. Subsequently, MYC induced melanogenesis, increased cellular size and complexity and senescence. Interestingly, we also found strong expression of MYC in regions of human nevi displaying high pigmentation and high expression of senescence marker p16. The results altogether show that MYC drives melanocytic differentiation and suggest that senescence is associated with differentiation. We discuss the implications into the mechanisms governing melanocytic differentiation and the development of melanoma.

Colonic tubular adenoma with incidental oxyntic gastric heterotopia.

Oxyntic gastric heterotopia (GH) in the colon is not common. Its presence in a colon tubular adenoma is even rare. A 73-year-old woman with a history of resected colon carcinoma underwent periodical colonoscopies for the removal of tubular adenomas for 12 years. In the last colonoscopy, a sessile, non-ulcerated polyp, centrally depressed, with a smooth surface, measuring 20 mm, located at 50 cm from the anal verge was excised. A histological study identified a tubular adenoma with focal low-grade dysplasia and ectopic gastric oxyntic epithelium. The GH, composed of parietal and chief cells, and was found incidentally. Oxyntic GH in a tubular adenoma is extraordinarily rare. To the best of our knowledge, there is only one previously published case. The main possible difficulties and∕or errors in the diagnosis include a tissue floater or a cross-contaminant. Precise diagnosis of oxyntic GH is basic for appropriate management. Diagnosis relies on histopathological examination. The immunohistochemical study for mucin 6 (MUC6) can confirm the nature of the epithelium. Oxyntic GH has the potential to produce serious complications including tumor development. However, GH is considered a benign disease and adenocarcinoma rarely occurs in the heterotopic mucosa. The optimal treatment of oxyntic GH associated with a tubular adenoma is endoscopic complete polypectomy.

Incidental mesonephric remnant hyperplasia of the jejunal mesentery: A diagnostic challenge.

Mesonephric remnants are embryonic vestiges of the mesonephric (Wolffian) ducts which regress during normal development. These remnants have been uncommonly reported in the female and male reproductive tract as a spectrum of morphologic lesions that can be misdiagnosed as carcinoma. One case of mesonephric remnant hyperplasia of the jejunal mesentery incidentally found in a 47-year-old man is herein reported. This is the first description of mesonephric hyperplasia arisen in the mesentery. The presence of ducts, tubules, and cysts lined by bland, epithelial, cuboidal cells with scant cytoplasm, and diffuse pseudoinfiltrative growth pattern can raise the possibility of neoplasia. Immunohistochemically, mesonephric epithelia have a characteristic staining. CD10 highlights the apical-luminal aspect of the cells. Besides, intense reactivity is showed for high-molecular-weight cytokeratin (CK), CK7, bcl2, and vimentin. The main differential diagnosis includes mesothelial hyperplasia, epithelial mesothelioma, well-differentiated neuroendocrine tumor, and infiltration due to acinar adenocarcinoma of the prostate. However, a detailed microscopic study with the aid of immunohistochemistry helps separate mesonephric remnants from malignant processes. The mesonephric hyperplasia of the mesentery we have reported adds to the spectrum of mesonephric remnants a new location. Familiarity with this lesion is indispensable to avoid overdiagnosis.

Esophageal spindle cell lipoma.

Symptomatic ordinary esophageal lipomas are rare tumors. Spindle cell lipomas (SCLs) of this location are even more infrequent. To our knowledge, only a previous esophageal SCL case has been reported. We describe herein the case of a 62-year-old woman with a long history of heartburn and feeling of abdominal distension. Preoperative investigations, including a Barium meal, gastroscopy, and echoendoscopy revealed a lipomatous polypoid mass attached to the middle esophageal segment. The lesion (3.5×2×1 cm) was excised endoscopically under deep sedation. The final histopathology diagnosis was pedunculated SCL. An accurate diagnosis of esophageal SCL is crucial to rule out malignant lesions, relieve symptoms, and undertake suitable treatment. The main differential diagnosis includes well-differentiated sclerosing liposarcoma, atypical spindle cell∕pleomorphic lipomatous tumor, giant fibrovascular polyp, and fat-forming solitary fibrous tumor. Although rare, SCL should be added to the list of lipomatous tumors that can affect the esophagus. Complete excision is the appropriate treatment.

Congestive Hepatopathy.

Liver disease resulting from heart failure (HF) has generally been referred as "cardiac hepatopathy". One of its main forms is congestive hepatopathy (CH), which results from passive venous congestion in the setting of chronic right-sided HF. The current spectrum of CH differs from earlier reports with HF, due to ischemic cardiomyopathy and congenital heart disease having surpassed rheumatic valvular disease. The chronic passive congestion leads to sinusoidal hypertension, centrilobular fibrosis, and ultimately, cirrhosis ("cardiac cirrhosis") and hepatocellular carcinoma after several decades of ongoing injury. Contrary to primary liver diseases, in CH, inflammation seems to play no role in the progression of liver fibrosis, bridging fibrosis occurs between central veins to produce a "reversed lobulation" pattern and the performance of non-invasive diagnostic tests of liver fibrosis is poor. Although the clinical picture and prognosis is usually dominated by the underlying heart condition, the improved long-term survival of cardiac patients due to advances in medical and surgical treatments are responsible for the increased number of liver complications in this setting. Eventually, liver disease could become as clinically relevant as cardiac disease and further complicate its management.

Abdominal elastotic lesions. A clinicopathologic study of 23 cases.

Abdominal elastotic deposits are uncommon lesions that often presents as polyps. They show three histological patterns: fibroelastosis, angioelastosis, and elastofibroma. We describe 23 cases including rare locations, such as mesentery, greater omentum, hernia sac, spleen, peripancreatic fat, and hypodermal fat. The age of the patients ranged from 49 to 93 years (mean, 76.8 years). Most lesions were discovered incidentally in the microscopic study. The most frequent locations were peritoneal subserosa (43.5%) and mesentery∕mesocolon∕greater omentum (39.1%). The most common pattern was fibroelastosis (69.6%) followed by angioelastosis (26.1%). We observed one case of omental elastofibroma. A review of the 14 abdominal elastofibromas described including our case revealed that the age of the patients ranged from 45 to 88 years (mean, 68.5 years). Female predominance is striking (M:F, 1:12). The most common site was the stomach (50%). The greater omentum (14.3%), small intestine (7.1%), and pancreas (7.1%) are very rare sites for this lesion. Only one case before ours has been published in the greater omentum. The size of the lesions ranged from 0.7 cm to 8 cm (mean 3.2 cm). In 36.4% of the cases located in the digestive tract, the mucosa did not show alterations. Ulcerations (36.4%) or polypoid excrescences (18.2%) were mostly observed. Six (42.9%) cases were asymptomatic and six (42.9%) cases simulated a neoplasm. Two cases were associated with elastofibromas in other locations. Differential diagnosis includes amyloidoma, elastofibrolipoma, mesenteric elastic vascular sclerosis in neuroendocrine tumors, diverticular disease elastosis, pseudoxanthoma elasticum, pulse granuloma, and digestive lesions in patients treated with D-Penicillamine.

Monophasic sarcomatoid eccrine porocarcinoma. Report of a case and literature review.

Sarcomatoid porocarcinoma (SP) is a rare subtype of porocarcinoma composed of both malignant epithelial and sarcoma-like components. To our knowledge, only eight cases of this neoplasm have been published, all of them biphasic. A 42-year-old man presented with a latero-cervical nodule that had been noted for about five months. Histopathological study revealed an infiltrative tumor within the dermis and hypodermis without connection to epidermis, whose diagnosis was monophasic sarcomatoid eccrine porocarcinoma (SEP). The study of nine cases de SP, including the present, revealed that the ages of the patients ranged from 42 to 89 years (mean 72.3 years). There was no clear difference in the incidence with respect to gender. The location of the tumor was most common in the head and neck, followed by lower extremity. The size ranged from 2.5 cm to 3.5 cm (mean 3 cm). At the time of diagnosis, six (66.7%) lesions were ulcerated. No case was clinically diagnosed. Residual poroma was present in six (66.7%) cases. Only one case showed apocrine differentiation. Mitoses and comedonecrosis were frequent. Of the cases published, only four had a follow-up of at least 16 months. One patient succumbed to the tumor. We report for the first time a case of monophasic SEP without epidermal connection. The patient presented a regional lymph node metastasis three months after excision. The main differential diagnosis includes primary dermal melanoma and other rare variants of cutaneous melanoma, primary cutaneous clear cell sarcoma, primary cutaneous synovial sarcoma, and cutaneous metastasis from visceral sarcomatoid carcinoma.

Synchronous Warthin tumor and papillary oncocytic cystadenoma in the ipsilateral parotid gland: an unreported association.

The occurrence of ipsilateral, synchronous, primary salivary gland tumors of different histological type is rare. In this report, we present the case of a 52-year-old male, established smoker, who showed simultaneously two different benign tumors in the right parotid gland. The patient complained of swelling below the angle of the mandible. Ultrasonography and computed tomography imaging revealed one mass of about 2.8 cm in the right gland. Besides, one small nodule in the left parotid gland was observed. The cytological diagnosis of the right gland was benign tumor, type IVa of the Milan system, consistent with Warthin tumor (WT). The clinical diagnosis was bilateral parotid WT. The histopathological (HP) study of the surgical specimen revealed a WT in combination with a papillary oncocytic cystadenoma (POC) in the right parotid. To our knowledge, this combination of tumors has not been previously reported. In our case, the association of tumors was not detected by imaging or fine-needle aspiration cytology (FNAC). WT and POC are difficult to distinguish by FNAC because their epithelial component is very similar. POC can resemble WT without lymphoid stroma, but the totality of HP features allows the differentiation of both processes. These tumors can be related to a common causal determinant and should not be considered as a result of chance. Both tumors follow favorable courses and are curable by surgical resection.

Histiocytoid cardiomyopathy and ventricular noncompaction presenting as sudden death in an adult male.

Histiocytoid/oncocytic cardiomyopathy (HCM) is a rare, distinctive arrhythmogenic disorder that presents as arrhythmia or sudden death in infants and children. Ventricular noncompaction (VNC) is a rare cardiomyopathy characterized by a thickened endocardial layer of noncompacted myocardium and a thin epicardial layer of compacted myocardium. Only six cases of the association of both cardiomyopathies have been reported previously in the literature. All these cases were in children. To the best of our knowledge, a case of HCM has not been described in the adult. We report the case of a 45-year-old man with an increased heart weight and involvement of both ventricles by HCM and VNC cardiomyopathy. Besides, multiple foci of myocardial disorganization were detected. He died suddenly while hiking. The association of both processes HCM and VNC was an unexpected finding at autopsy. The death was linked to functional abnormalities of the cardiac histiocytoid cells, and it was favored by a state of abnormal development of the heart.

Hessian analysis for the delineation of amorphous anomalies in optical coherence tomography images of the aortic wall.

The aortic aneurysm is a disease originated mainly in the media layer of the aortic wall due to the occurrence of degraded areas of altered biological composition. These anomalous regions affect the structure and strength of the aorta artery, being their occurrence and extension proportional to the arterial vessel health. Optical Coherence Tomography (OCT) is applied to obtain cross-sectional images of the artery wall. The backscattering mechanisms in tissue make aorta images difficult to analyze due to noise and strong attenuation with penetration. The morphology of anomalies in pathological specimens is also diverse with amorphous shapes and varied dimensions, being these factors strongly related with tissue degradation and the aorta physiological condition. Hessian analysis of OCT images from aortic walls is used to assess the accurate delineation of these anomalous regions. A specific metric of the Hessian determinant is used to delineate degraded regions under blurry conditions and noise. A multiscale approach, based on an anisotropic Gaussian kernel filter, is applied to highlight and aggregate all the heterogeneity present in the aortic wall. An accuracy estimator metric has been implemented to evaluate and optimize the delineation process avoiding subjectivity. Finally, a degradation quantification score has been developed to assess aorta wall condition by OCT with validation against common histology.

Incidental diffuse esophageal intramural pseudodiverticulosis. A rare autopsy finding / Pseudodiverticulosis intramural difusa esofágica incidental. Un raro hallazgo de autopsia

Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition of uncertain etiopathogenesis which usually presents with either intermittent or progressive dysphagia. A review of the literature revealed very few studies of its histopathology. We report the case of a 70-year-old diabetic man who died after a road traffic accident. The patient had no history of dysphagia. The entity was discovered incidentally during the medico-legal autopsy. The esophagus showed numerous dilated pseudodiverticula confined to the submucosa and lined by both stratified squamous and cuboidal epithelium. EIPD can remain stable and asymptomatic. This case demonstrates the importance of a thorough investigation during a forensic autopsy (AU)

La pseudodiverticulosis intramural esofágica (PDIE) es un raro proceso de etiopatogénesis incierta que generalmente se manifiesta con disfagia intermitente o progresiva. Una revisión de la literatura ha revelado muy pocos casos publicados mostrando el aspecto histológico de esta condición. Presentamos el caso de un varón de 70 años de edad, diabético, que falleció tras un accidente de tráfico. El paciente no tenía historia de disfagia. La entidad fue descubierta incidentalmente al practicar la autopsia médico-legal. El esófago mostraba numerosos pseudodivertículos confinados a la submucosa y tapizados por epitelio estratificado escamoso y cuboideo. La PDIE puede permanecer estable y asintomática. Este caso demuestra la importancia de una exhaustiva investigación en la autopsia forense (AU)

Incidental vaginal müllerianosis.

Müllerianosis is the term used to designate lesions composed of an admixture of two or three types of müllerian-derivation glands in heterotopic location. In this report, we describe a case of incidental vaginal müllerianosis in a 59-year-old woman who underwent rectosigmoidectomy for rectal adenocarcinoma. In the vaginal cuff removed for neoplastic invasion, a separate multilocular mass measuring 1.5cm was found. The microscopic examination of the vaginal wall revealed endosalpingeal, endocervical and endometrial dilated or cystic glands with predominance of the endosalpingeal epithelium. Müllerian epithelium showed positivity for cytokeratins 7 and 8/18, high molecular weight cytokeratin, estrogen receptor alpha, and androgen receptor. The periglandular stroma was condensed and reactive for smooth-muscle actin, h-caldesmon, and CD10. To the best of our knowledge, a case of vaginal müllerianosis has not been previously reported. This lesion should be differentiated form vaginal adenosis and primary well-differentiated vaginal adenocarcinoma. The vagina should be added to the list of locations in which müllerianosis can be observed.

Extracutaneous intravascular histiocytosis of the aortic valve: Report of two cases.

Intravascular histiocytosis (IVH) is a rare condition of uncertain pathogenesis often associated with rheumatoid arthritis (RA) exclusively observed in the skin. In a retrospective study of 207 consecutive cases of aortic valve disease, we observed two cases of IVH characterized by the presence of thin-walled, dilated blood vessels containing collections of CD68+ and CD163+ mononuclear histiocytes. Immunostains for CD31, CD34, and D2-40 confirmed the intravascular location of these histiocytes. One of the two cases was associated with RA. This case was observed among 41 cases of RA with calcific aortic valve stenosis. The other case was detected among 152 cases of calcific aortic valve stenosis in isolation. A total of 14 valves showed no calcification. IVH can manifest in the aortic valve and be associated with systemic disease. In contrast to other cases, the vessels observed in this study exhibited negative expression of the lymphatic marker D2-40. Our findings expand on the previously described location features of IVH.

Gastric pyogenic granuloma: Report of two cases and review of the literature.

Pyogenic granuloma (PG) is a polypoid lobular capillary hemangioma rarely described in the stomach. We report two cases aged 72 and 66 years. A review of the literature on gastric PG, including the present cases, yielded ten patients. There were six males and four females. The age of the patients ranged from 35 to 82 years with a mean of 58.9 years. The lesions were all solitary, except one case of multiple lesions in the corpus and antrum. PG can be located in any part of the stomach. The most common site was the antrum. The mean maximum diameter of the lesions was 14.5mm (range 7-30mm). Most lesions were pedunculated. Pain or discomfort (epigastric, right upper quadrant or chest), upper gastrointestinal bleeding, and melena were the most common clinical symptoms. Iron deficiency anemia was the rule, often requiring blood transfusion. Five patients underwent snare polypectomy, four endoscopic mucosal resection, and one laser irradiation. The follow-up ranged from two weeks to two years. There were no recurrences. Pathologists should be familiar with this condition in order to avoid overdiagnosis as a malignant vascular tumor.

Incidental Melanocytic Nevi in Hemorrhoidectomy Specimens.

BACKGROUND: Benign melanocytic nevi (MN) of the anal canal are exceptional and require adequate differential diagnosis. There are no data on incidence of these lesions. Only a single case report of hemorrhoid with an MN has been reported. The necessity of routine pathologic evaluation of hemorrhoidectomy specimens has been questioned. MATERIAL AND METHODS: The authors undertook a retrospective histologic study of the hemorrhoidal tissue obtained in a series of 1918 consecutive hemorrhoidectomies performed between January 2004 and November 2012. RESULTS: Incidental hemorrhoidal MN were detected in 4 (0.21%) patients. The ratio observed was 1 nevus in 480 specimens. Lesions were intradermal or purely junctional in nature. There were no mitoses or architectural disorder. An intradermal nevus showed localized pagetoid melanocytes. The mean age of the patients was 56.5 years (range 47-73 years). The mean size of nevi was 5.86 mm (range 1.89-13.86 mm). All cases were present in external hemorrhoids. CONCLUSIONS: Although uncommonly, incidental MN can be observed in hemorrhoidal tissue. They may show features of flexural nevi and pagetoid melanocytes. Routine histopathological study of hemorrhoidectomy specimens would help to detect benign or malignant melanocytic tumors of the anal canal as these neoplasms can be easily missed clinically. Furthermore, this practice would allow early diagnosis of significant associated processes.

Low-grade serous primary peritoneal carcinoma incidentally found in a hernia sac.

Very rarely, a primary peritoneal serous carcinoma can be observed in a hernia sac. We herein describe a low-grade serous primary peritoneal carcinoma incidentally found in a postmenopausal woman following examination of the femoral hernia repair sac. Our case is significant for its unusual presentation. The lesion initially appeared as a 0.3-cm tumor that disseminated in the peritoneum, persisted, and progressed for 75 months. The absence of ovarian disease indicated a primary peritoneal origin. Tumor cells were immunohistochemically positive for PAX8, claudin-4, and VE1, excluding the possibility of being of mesothelial origin. Recognition that a low-grade serous primary peritoneal carcinoma can be incidentally found in a hernia sac should simplify future diagnoses. Immunohistochemistry is helpful in making the correct diagnosis.

Primary renal myxofibrosarcoma.

Kidney sarcomas are rare, representing only 1% of malignant renal tumors. We herein report the case of a 70-year-old woman that was admitted for an episode of confusion in relation to hypertensive encephalopathy. Imaging investigations revealed a large mass in the right kidney with extension to the renal hilum. The patient underwent right open radical nephrectomy. The histopathologic study disclosed a 15-cm, myxoid and cellular, pleomorphic tumor with elongated, curvilinear, thin-walled vessels, and focal necrosis that involved the upper and middle segments of the kidney. Immunohistochemically, the tumor cells showed strong positivity for vimentin, bcl2 protein (nuclear staining pattern), CD34, CD99, and alpha-methylacyl coenzyme A racemase. The tumor was diagnosed as myxofibrosarcoma (MFS) grade 2 according to the FNCLCC system. To the best of our knowledge, this is the first report of an MFS arising from the kidney. Thus, MFS is an uncommon soft tissue tumor that can exceptionally arise from the kidney. The differential diagnosis with other myxoid tumors is of vital importance because it includes lesions with subtle differences and extremely variable biological behavior. Radical surgery is the treatment of choice. Long-term follow-up is recommended because of the tumor's capability for local recurrence and distant metastasis.

Colorectal adenomas contain multiple somatic mutations that do not coincide with synchronous adenocarcinoma specimens.

We have performed a comparative ultrasequencing study of multiple colorectal lesions obtained simultaneously from four patients. Our data show that benign lesions (adenomatous or hyperplastic polyps) contain a high mutational load. Additionally multiple synchronous colorectal lesions show non overlapping mutational signatures highlighting the degree of heterogeneity between multiple specimens in the same patient. Observations in these cases imply that considering not only the number of mutations but an effective oncogenic combination of mutations can determine the malignant progression of colorectal lesions.