Primary Cilia as a Tumor Marker in Pituitary Neuroendocrine Tumors.

Pituitary neuroendocrine tumors (PitNETs) account for approximately 15% of all intracranial neoplasms. Although they usually appear to be benign, some tumors display worse behavior, displaying rapid growth, invasion, refractoriness to treatment, and recurrence. Increasing evidence supports the role of primary cilia (PC) in regulating cancer development. Here, we showed that PC are significantly increased in PitNETs and are associated with increased tumor invasion and recurrence. Serial electron micrographs of PITNETs demonstrated different ciliation phenotypes (dot-like versus normal-like cilia) that represented PC at different stages of ciliogenesis. Molecular findings demonstrated that 123 ciliary-associated genes (eg, doublecortin domain containing protein 2, Sintaxin-3, and centriolar coiled-coil protein 110) were dysregulated in PitNETs, representing the upregulation of markers at different stages of intracellular ciliogenesis. Our results demonstrate, for the first time, that ciliogenesis is increased in PitNETs, suggesting that this process might be used as a potential target for therapy in the future.

Pancreatic panniculitis revisited: A series of 34 patients.

BACKGROUND: Pancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue. METHODS: In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records. RESULTS: A total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore-Hoeppli phenomenon. CONCLUSIONS: We present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore-Hoeppli is an additional clue to its diagnosis.

Graft-versus-host disease-associated angiomatosis with striking lipomatous metaplasia.

Sclerodermatous graft-versus-host disease (GvHD) is one of the many clinicopathological variants of chronic GvHD. One of the rarest forms of this variant is GvHD-associated angiomatosis (GvHD-AA). We describe the case of a 62-year-old male with sclerodermatous GvHD who presented, in consecutive years, two different lesions that showed characteristics of GvHD-AA. The first lesion fitted perfectly with the previously known features of this rare entity. However, the second lesion was more interesting, as the angiomatoid lesion was surrounded by newly appeared adipocytes, something not previously described. The appearance of this peculiar adipose tissue may be explained as related to an important dermal atrophy, as a concomitant appearance of a lipomatous nevus and GvHD-AA, or, finally, as mature adipose tissue related to a previous inflammatory process, that is, lipomatous metaplasia. Both lesions were diagnosed as GvHD-AA, and the second one was considered to be associated with dermal lipomatous metaplasia. We also considered whether hypoxia could be related to both lesions. In the present report, we review previously published cases of GvHD-AA and discuss the different hypotheses that could explain the appearance of metaplasia associated with the second lesion.

Bilateral Facial Apocrine Fibrosing Hamartoma Mimicking Microcystic Adnexal Carcinoma.

An otherwise healthy 50-year-old woman was evaluated for the presence of 2 erythematous, and slightly pruritic plaques, involving both cheeks for 30 years. Left-side skin biopsy showed a diffuse proliferation of ductal structures horizontally arranged and involving the reticular dermis that resembled tubular adenoma embedded in a sclerotic stroma and surrounded by a peculiar periductal desmoplasia. Nuclear atypia or mitosis was not found. Contralateral biopsy showed identical findings. Differential diagnosis included microcystic adnexal carcinoma (MAC) and plaque-like syringoma and a peculiarly horizontally arranged tubular adenoma. We ruled out MAC as the lesions were long-standing, without infundibular cysts, solid strands, or perineural infiltration. Our case closely resembled those previously described as sweat duct proliferation associated with aggregates of elastic tissue and atrophoderma vermiculatum, although striking differences were observed, as our case did not present aggregates of elastic tissue, did not involve the papillary and superficial reticular dermis, and presented evidences of decapitation secretion as a sign of apocrine differentiation. We consider our case as a MAC simulator and we propose the descriptive name of bilateral facial apocrine fibrosing hamartoma.

Immunohistochemical Study of 2 Cases of Coxsackie A6-Induced Atypical Hand-Foot-and-Mouth Disease.

An atypical clinical variant of hand-foot-and-mouth disease (HFMD) with more extensive lesions and affecting adults has emerged during the past years, usually associated to the Coxsackievirus serotype A6 (CV-A6). We present a 19-year-old woman with a 3-day evolution eruption of papulovesicular lesions, which first appeared around the mouth and frontal area and rapidly spread. In addition, we present a 61-year-old man with a 4-day evolution asymptomatic eruption of papulovesicular lesions in both the hands and feet after suffering a cold 1 week before. Skin biopsies of both patients showed intraepidermal vesicles with spongiosis and ballooning, leading to reticular degeneration, apoptotic keratinocytes, and epidermal necrosis of the upper layers with neutrophil sloughing. Immunohistochemical studies for Coxsackie, Enterovirus, herpes virus, adenovirus, and measles were all negative. Cultures of blister fluid, reverse transcription polymerase chain reaction of skin biopsies, blood tests and serologies for exanthematic virus, and serum viral arrays were also negative. Only reverse transcription polymerase chain reaction of blister fluid confirmed Cocksakie A6. In conclusion, immunohistochemical studies with the commercially available viral antibodies do not seem to be useful in atypical HFMD cases. In these cases, to determine the typical histopathological features in HE is the fastest diagnostic aid.

Skeletal muscle and solitary bone metastases from malignant melanoma: multimodality imaging and oncological outcome.

Malignant melanoma solitary metastases to bone or skeletal muscle occur in 0.8% of patients. The aim of this study was to evaluate features of skeleton and muscle metastases with multimodality imaging and review the oncological outcome. Thirteen patients with melanoma metastases from January 2006 to February 2016 were included. Histologic confirmation was obtained. Imaging studies included computed tomography (CT), MRI, and/or positron emission tomography/CT. Treatment received and BRAF status were recorded. Differences in BRAF status and overall survival (OS) were analyzed using the χ-test. Associations between OS and metastases were analyzed using Cox proportional models. Nine (69%) patients showed osseous involvement. Lower extremity bones were affected in three (23%) patients: first toe, right calcaneal spurs, and knee. The spine was involved in three (23%) patients. In two (15%) patients, the pelvic bones were involved. In one (8%) patient, the temporal bone was affected. Nine (70%) patients had a history of malignant melanoma, with a median time to progression of 28 months. The median OS was 18 months: 24 months in patients with a history of melanoma and 3 months in patients with metastases at first diagnosis. The median follow-up duration was 28 months. BRAF mutant versus wild-type tumors showed significant differences in OS (P=0.03). The hazard ratio for death in the metastatic group at diagnosis was 6.83, 95% confidence interval: 1.060-144.072 (P=0.04). Solitary metastases from melanoma to the skeleton and muscle are rare. CT, MRI, and positron emission tomography/CT are useful for the evaluation of musculoskeletal findings. Image findings are not definitive for diagnosing a malignant solitary lesion; thus, a pathologic confirmation with a biopsy is recommended.

Hypophysitis following Treatment with Ustekinumab: Radiological and Pathological Findings.

CONTEXT: Ustekinumab is a human IgG1 monoclonal antibody that targets interleukin (IL)-12 and IL-23, which may be useful in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, and Crohn's disease. Hypophysitis is an immune-derived inflammatory condition of the pituitary gland that may lead to pituitary dysfunction. With the increasing use of immunotherapy, it is possible that this and other new immune-related adverse events (IRAEs) arise, although the mechanisms involved are still incompletely defined. CASE DESCRIPTION: A 35-year-old male, with a previous history of severe plaque-psoriasis who had started treatment with ustekinumab 4 months before, complained of progressive and persistent headache. Brain magnetic resonance imaging (MRI) was unremarkable. One year later, a new MRI was performed due to headache persistence, which revealed a homogenous and diffuse pituitary enlargement, with suprasellar extension and optic chiasm involvement, blurring of the pituitary stalk, absence of clear differentiation between the anterior and posterior lobes, and no signs of hemorrhage or adenomas. Endocrine evaluation was consistent with panhypopituitarism. Work-up of infiltrative and infectious diseases was negative. Follow-up MRI revealed an increase in the pituitary enlargement and transsphenoidal surgery was performed. Pathological findings revealed an intense fibrosis and a chronic inflammatory infiltrate, but no evidence of adenoma, granuloma, or acid fast bacilli. Immunohistochemical staining showed a combined T-cell (CD3+, CD4+) and B-cell (CD19+, CD20+) phenotype. CONCLUSION: We suggest a novel IRAE of ustekinumab, with full radiological and immunopathological iconography, which may be mediated by the complex interaction between different immunological processes.

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.

BACKGROUND: Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. CASE: A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity. CONCLUSION: Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report.

Vasculopathies, cutaneous necrosis and emergency in dermatology.

Most emergencies in dermatology comprise a variety of entities with a usually benign course. However, vasculopathies and vasculitis are not common, but they could represent respectively 1.9% and 4.4% of these entities according to some studies of Emergency Dermatology Department. They become an important disease which has to be identified early to establish appropriate management and treatment. Some of them are well known, such as the leukocitoclastic vasculitis, Schölein-Henoch, panarteritis nodosa, antineutrophil cytoplasmic antibody associated vasculitis, giant cell arteritis, cryoglobulinemic vasculitis and antiphospholipid syndrome. More frequent vasculopathies are livedoid vasculopathy, pigmented purpuric dermatosis and calciphylaxis. Less common ones are caused by interferon and cholesterol crystal embolization. Others are very infrequent as Degos disease and Sneddon Syndrome. Among the more recently described ones there are deficiency of adenosine deaminase type 2 and crystalglobulinemia. The other group is composed of vasculopathies associated to microorganism as infective endocarditis, septic vasculopathy, aspergillosis, fusariosis, strongiloidosis, ecthyma gangrenosum, lucio phenomenon of leprosy and necrotic arachnidism. Finally, among these entities we can also find diseases associated with proinflammatory stages as disseminated intravascular coagulation, myeloproliferative disorders, intravascular lymphoma, metastasis intravascular. When we face cutaneous lesions characterized by reticulated violaceous lesions, palpable purpura or cutaneous necrosis, a careful clinico-pathological correlation as well as some laboratory or radiological tests are mandatory to further delineate a diagnosis and a proper first line empirical treatment.

[Myelopathy secondary to an aneurysmal bone cyst of thoracic spine]. / Mielopatía secundaria a un quiste óseo aneurismático espinal dorsal.

INTRODUCTION: Spinal aneurysmal bone cysts are very infrequent benign osteolytic lesions consisting of blood-filled cavities that are separated by osteo-connective septa and osteoclast-type giant cells. Clinically they manifest with local pain, neurological symptoms secondary to spinal cord compression, and fractures, deformities and vertebral instability. We report a case of an aneurysmal bone cyst in the thoracic spine with neurological signs and symptoms treated by means of a full microsurgical resection, with no associated neurological sequelae. CASE REPORT: A 47-year-old woman, with no previous history of traumatic injuries, who was examined following several weeks with clinical signs and symptoms of paraesthesia in the lower limbs. Thoracic magnetic resonance imaging revealed the existence of a lytic lesion with clearly defined edges and marginal sclerosis in T4, in addition to involvement of the posterior vertebral elements and compression of the underlying spinal cord. The whole lesion was removed surgically, and the sensitive clinical symptoms disappeared after the procedure. The definite pathological diagnosis was spinal aneurysmal bone cyst. CONCLUSION: Despite their low incidence, aneurysmal bone cysts of the spine must be taken into account in the differential diagnosis of spinal bone tumours as a possible cause of subacute or chronic compressive myelopathy. Full surgical removal of the tumour is considered the preferred treatment, which is often curative and is associated with a good prognosis of the patient in the long term.

TITLE: Mielopatia secundaria a un quiste oseo aneurismatico espinal dorsal.Introduccion. Los quistes oseos aneurismaticos espinales son lesiones osteoliticas benignas muy infrecuentes constituidas por cavidades hematicas limitadas por septos osteoconectivos y celulas gigantes tipo osteoclastos. Clinicamente se manifiestan con dolor local, sintomas neurologicos secundarios a compresion medular, asi como fracturas, deformidades e inestabilidad vertebral. Presentamos un caso de quiste oseo aneurismatico espinal dorsal con sintomatologia neurologica, tratado mediante una reseccion microquirurgica completa, sin secuelas neurologicas asociadas. Caso clinico. Mujer de 47 años, sin antecedentes traumaticos previos, valorada por presentar un cuadro de parestesias de los miembros inferiores de semanas de evolucion. El estudio radiologico de resonancia magnetica dorsal demostro la existencia de una lesion litica de bordes bien delimitados y esclerosis marginal en D4, con afectacion de los elementos posteriores vertebrales y compresion del cordon medular subyacente. La lesion fue extirpada en su totalidad, con desaparicion de la clinica sensitiva tras la intervencion. El diagnostico anatomopatologico definitivo fue quiste oseo aneurismatico espinal. Conclusion. A pesar de su baja incidencia, los quistes oseos aneurismaticos espinales deben considerarse, en el diagnostico diferencial de los tumores oseos espinales, como una posible causa de mielopatia compresiva subaguda o cronica. La reseccion tumoral completa se considera el tratamiento de eleccion, el cual con frecuencia es curativo y asocia un buen pronostico del paciente a largo plazo.

Eccrine porocarcinoma with extensive cutaneous metastases.

BACKGROUND: Eccrine porocarcinoma (EPC) is an uncommon malignant neoplasm that originates in the intraepidermal portion of the eccrine sweat duct. Although porocarcinoma is a slow-growing tumor, up to 20% of cases can metastasize to regional lymph nodes, thus increasing mortality. METHODS: We describe the clinical and histopathological features and clinical course of three cases of extensive metastatic EPC diagnosed in our department over the last 10 years. RESULTS: All three patients were women aged 89-96 years. They had numerous skin tumors on the left leg that were histologically and immunohistochemically diagnosed as metastatic EPC. Only one patient had a history of primary porocarcinoma, which had been excised 6 years earlier. The remaining two patients had a previous lesion diagnosed as squamous cell carcinoma. We treated the patients with palliative radiotherapy and/or chemotherapy. Only one patient is currently alive. CONCLUSIONS: The cases of cutaneous and regional metastatic EPC we present occurred in elderly women with major involvement of the left leg. The third case is noteworthy, as the patient presented a long latency period before metastases appeared. Difficulties in the clinical diagnosis--and occasionally histological diagnosis--of primary EPC could delay more aggressive treatment, although optimal treatment does not always guarantee a good prognosis.

Trigger finger following partial flexor tendon laceration: Magnetic resonance imaging-assisted diagnosis.

INTRODUCTION: Post-traumatic trigger finger is considerably rarer than normal trigger finger. The diagnosis is usually made on a clinical basis. This can be obscured; however, by concurrent pathological conditions. We report a case of post-traumatic trigger finger in which diagnosis was aided by magnetic resonance imaging (MRI). PRESENTATION OF CASE: Our patient is a 32-year-old male who had a previous laceration with a subsequent surgery for infectious tenosynovitis. The MRI showed the impinging tendon tag. Surgical excision of the tag successfully solved the case. DISCUSSION: The use of imaging studies for the diagnosis of post-traumatic trigger finger has been previously reported, the authors described a variation on the contour of the pulley system. The full lacerated tendon tag can be seen on our patient's MRI. CONCLUSION: On this case, the use of MRI was a useful aid for the differential diagnosis of post-traumattic trigger finger.