[Nested variant Transitional Cell Carcinoma. Report of two cases and bibliographic review.] / El carcinoma urotelial variante en nidos(NESTED). Presentación de dos casos y revisión de la literatura.

OBJECTIVE: Nested type transitional cell carcinoma of the bladder is a rare histological variant among bladder tumors. Although clinical presentation is similar to the other bladder tumors, its macroscopic appearance may be equivocally benign, with submucosal growing which is difficult to detect on cystoscopy, so that diagnosis may be delayed. METHODS: We present the characteristics of nested type transitional cell carcinoma and review the differential diagnosis for this entity with possible counterfeiters. RESULTS: In this article, we report two cases of nested type transitional cell carcinoma that presents, in one of them, all three growing patterns. CONCLUSIONS: Microscopically nested transitional cell carcinoma is characterized by a cell distribution forming nests and tubules. They generally present low cytologic atypia simulating a low grade urothelial carcinoma, or benign bladder lesions such as von Brunn nests or nefrogenic adenoma.

[Adenoma metanephric: Report of 2 cases and bibliographic review.] / Adenoma metanefrico: presentación de 2 casos y revisión de la literatura.

OBJECTIVE: Two cases of metanephric adenoma are presented, a rare benign renal tumor, and a literature review is done under the current WHO classification (2016). METHODS: Standard histopathological study was performed with hematoxylin-eosin and immunohistochemistry to analyze the expression of WT, Vimentin, Racemase, CK7, CD10 and RCC. RESULTS: Neoplasms of 3 and 4.5 cm, histologically, exhibiting tubulopapillary architecture. There was no evidence of significant nuclear atypia and mitotic figures. Immunohistochemical study showed positive immunoreaction for WT1 and Vimentin in tumor cells. CONCLUSIONS: Two new cases of metanephric adenoma are presented and a review of the literature was performed in order to discuss the prognosis and differential diagnosis of metanephric adenoma. This is a rare tumor and its diagnosis lies on its morphology and its immunohistochemical profile.

Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature.

DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10-30%) and of varying intensity (1+ to 2+). In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.

[Major complications of acquired renal cystic disease: Wünderlich syndrome and papilar carcinoma.] / Complicaciones de la enfermedad renal quística adquirida: síndrome de Wünderlich y carcinoma papilar.

OBJETIVE: We report a case of acquired renal cystic disease associated with renal dialysis and endstage renal disease. The patient suffered the two major complications related with acquired renal cystic disease; hemorrhage and renal carcinoma. METHODS: Our case is a patient with acquired renal cystic disease, single kidney after surgery for renal clear cell carcinoma four years earlier, who developed a Wünderlich syndrome (WS). RESULTS: The histological study of the nephrectomy specimen showed a renal papillary carcinoma in the context of acquired renal cystic disease after surgery for a WS. CONCLUSIONS: Renal hemorrhage is a serious complication that can lead to a fatal outcome. Patients undergoing dialysis should be monitored actively due to the risk of developing acquired renal cystic disease and associated complications.

[Subclinical acute intermittent porphyria. An uncommon cause of chronic hepatitis]. / Porfiria aguda intermitente subclínica. Etiología inusual de hepatitis crónica.

Acute porphyria is a term that encompasses a group of hereditary disorders involving defects in heme metabolism, characterized by acute episodes of abdominal pain, acute hypertension, tachycardia and neuropsychiatric disorders, sometimes leading to convulsions, ascending paralysis and coma. Misdiagnosis or delayed diagnosis can seriously worsen prognosis. We report the case of a woman with subclinical acute intermittent porphyria and chronic hepatitis incidentally diagnosed due to transaminase elevation on laboratory analysis.

Gastrointestinal stromal tumors: morphological, immunohistochemical and molecular changes associated with kinase inhibitor therapy.

Recurrent or metastatic GISTs are currently treated with kinase inhibitors since they achieves disease control in 70-85% of patients but this response depend on KIT and PDGFRA gene mutation status. We review the morfological and molecular findings associated to kinase inhibitors administration in GISTs based on the literature on Medline and authors' own experience. The initial response to kinase inhibitors (imatinib mesylate, Gleevec, Novartis) usually is partial and depend on the mutational KIT or PDGFRA state. Amongst patients wih KIT mutations, the best results are achived in those harboring exon 11 (85%) and exon 9 (45%) mutations. GISTs harboring PDGFRA gene mutations generally respond favorably except those involving the Asp842Val mutation. In the absence of KIT/PDGFRA gene mutations, partial response or disease stabilization is reported in 23% and 50% of patients, respectively, and disease progression in 19%. Histological examination of tumors displaying an initial response to imatinib reveals a highly-variable reduction in the number of tumor cells, a decline in the proliferative index, myxohyaline or sclerohyaline stroma, and a varying degree of bleeding and edema, necrosis and cystification. 72% of patients with initial good response to imatinib, display metastases or new nodule growth within an existing clinically-quiescent tumor after 12-36 months of treatment. This secondary resistance is characterized by a number of well-defined morphological and molecular changes. Histologically, the new growths display increased mitotic activity, pleomorphism, an epithelioid or mixed phenotype and persistent KIT expression although more rarely, dedifferentiation and loss of KIT expression (Fig. 4), as well as trans-differentiation into a rhabdomyosarcoma or epithelial phenotype has been reported. Molecularly, 46-67% of patients present additional KIT mutations, generally in the kinase domain (exons 13, 14 and 17) but also in the ATP-binding domain (exons 15,16) of the same allele. Secondary PDGFRA mutations are very rare. Secondary mutations have not been observed in GISTs not harboring KIT/PDGFRA mutations, or in tumors displaying an unusual morphology or loss of CD117 expression. A number of studies highlight the presence of different resistance mutations within different new tumor nodules, as well as the simultaneous development of distinct resistant tumor subclones within a single lesion (acquired polyclonal resistance). Secondary mutation in genes other than KIT/PDGFRA has only been reported in BRAF (Val600Glu).

Interferon-induced cutaneous sarcoidosis in melanoma.

Interferon-induced cutaneous sarcoidosis in the adjuvant treatment of melanoma is a rare side effect. We present the case of a patient who developed two histologically confirmed subcutaneous sarcoid nodules 15 months after starting adjuvant therapy with interferon for lymph node metastatic melanoma in which the primary tumor was not known. The extension study, coinciding with occurrence of the nodules, showed no systemic sarcoidosis. This therefore represents the second reported case of interferon-induced cutaneous sarcoidosis in melanoma therapy. As computed axial tomography-PET or other imaging techniques are unable to differentiate between the radiological signs of melanoma metastasis and sarcoidosis, histological evaluation of the granulomatous lesions is essential with a view to avoiding unnecessary treatments.