Hematopoietic cell transplant for reversal of liver fibrosis in a pediatric patient with erythropoietic protoporphyria.

BACKGROUND: EPP is a rare disorder of heme biosynthesis in which patients present with disabling photosensitivity. A subset of patients develop severe liver disease with progressive liver failure necessitating an OLT. A HCT can potentially cure EPP by replacing the native bone marrow, which is the primary site of heme synthesis. However, due to concerns for inherent risks of treatment-related toxicities, the use of HCT has been reserved for patients undergoing an OLT to avoid disease recurrence in the hepatic graft. Data for HCT in EPP are lacking, particularly in the pediatric population. CASE (METHODS/RESULTS): We present the case of a 12-year-old patient with EPP photosensitivity and cirrhosis, whom we successfully treated with pre-emptive allogeneic HCT, significantly improving the patient's quality of life. We used a matched-unrelated donor bone marrow-derived graft. Our patient achieved full donor peripheral blood chimerism and has not had any evidence of GVHD. In addition to resolution of photosensitivity, our patient had reversal of liver fibrosis which we feel was largely due to intervention at an early stage of compensated cirrhosis. CONCLUSION: Our case highlights the successful application of a known RIC regimen to this rare disorder that was well tolerated with sustained donor engraftment. It also emphasizes the importance of timing for HCT in patients with EPP and liver fibrosis. HCT should be considered early in pediatric patients with EPP-hepatopathy to prevent progression to liver failure and need for OLT with lifelong immunosuppression.

Synchronous Colon and Pancreatic Rosai-Dorfman Disease.

Rosai-Dorfman disease (RDD) is primarily a disease of massive lymphadenopathy and sinus histiocytosis. It has been documented across extranodal organ systems, but it rarely has been described in the gastrointestinal tract only. Here is the unique case of 2 primary extra-nodal masses found simultaneously in the pancreas and right colon of a patient without the classical concomitant lymphadenopathy. We also reviewed the literature and found 11 additional cases of pancreatic RDD. This is the first male case and 1 of only 2 cases of RDD presenting synchronously in 2 distinct locations within the gastrointestinal system. Furthermore, we discuss the potential use of fine needle aspiration (FNA) and core sample biopsies in confirming a diagnosis of RDD.

Hobnail cells in encapsulated papillary thyroid carcinoma: Report of 2 cases with immunohistochemical and molecular findings and literature analysis.

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland with most tumors behaving in an indolent fashion. However, morphologic variants have been described, such as tall cell, diffuse sclerosing, columnar cell etc. which are biologically more aggressive. One of these variants includes the more recently described hobnail variant (HVPTC) which shows micropapillae and presence of large cells with apically placed hyperchromatic nuclei, reverse polarity, and eosinophilic cytoplasm, akin to hobnail cells. The presence of >30% hobnail cells in a PTC deserves categorization as a hobnail variant. This variant is usually associated with extra thyroidal extension, lymphovascular invasion and lymph node metastasis. We describe the pathologic and molecular features of two cases of encapsulated PTC with hobnail cells in a 68 year old male and a 22 year old female (30% and 10% hobnail cells respectively). Both cases presented as low stage (pT2) tumors and showed no aggressive features like lymph node metastasis, or extrathyroidal extension (ETE) at the time of presentation. Tumors in both cases showed presence of BRAFV600E mutation, absence of RAS and/or TP53 mutations, and were negative for RET and PAX88/PPARG gene rearrangements.

Salivary duct carcinoma: A case report of oncocytic variant with possible treatment implications and review of literature.

Salivary duct carcinoma (SDC) is an aggressive malignancy, resembling high-grade ductal carcinoma of the breast. Histologically, it shows cords and nests with cribriforming, marked nuclear atypia, comedonecrosis, perineural, and lymphovascular invasion. We report a rare case of SDC in a 61-year-old woman presenting with facial asymmetry, dysphagia, and cervical lymphadenopathy. Imaging showed an ill-defined infiltrating mass in parotid gland and multiple enlarged cervical lymph nodes. Histologically, the largest focus of tumor consisted of an intra-parotid lymph node replaced by sheets of bland appearing oncocytic tumor cells with abundant cytoplasm, centrally placed nucleus, and single prominent nucleolus. No mitotic figures were identified and focal areas showed nests with comedonecrosis and desmoplastic stromal response. Tumor showed strong positive staining for androgen receptor, CK7 and GATA-3. In addition, tumor stained strong positive for Her2neu making the patient amenable to Herceptin. NGS detected mutation in HRAS (p.Q61R) and a novel, not previously reported mutation in PIK3CA, (exon 21, p.H1047L). This case represents a rare presentation of SDC with bland cellular morphology unlike the usual associated high grade features. In addition, it reemphasizes the importance of androgen receptor in differential diagnosis from its mimics like oncocytic carcinoma and oncocytic variant of mucoepidermoid carcinoma. Further, Her2neu immunohistochemical status can be used for diagnosis as well as guide targeted therapy in these aggressive tumors.

Hepatotoxicity of illegal home-made alcohols.

OBJECTIVE AND AIM: Alcohol-related hepatotoxicity is not only caused by excessive alcohol consumption but also caused and even accelerated by hepatotoxic ingredients other than ethanol. Concentrations of hepatotoxic substances might be significantly high, particularly in illegally produced home-made alcohols. In this study we aim to analyze the hepatotoxic effects of a home-made alcohol traditionally called "bogma raki" in Turkey. MATERIALS AND METHOD: Fifty Wistar albino male rats were used. Five groups were randomly formed with ten animals in each. Besides laboratory diets, groups were fed as follows: Group 1 (control group) distilled water; Group 2 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day); Group 3 bogma raki with distilled water (%44 (v/v), 9.2 ml/kg/day)+walnut (10 g/kg/day); Group 4 whisky with distilled water (%40 (v/v), 9.2 ml/kg/day); Group 5 distilled water + walnut (10 g/kg/day), for 28 days. The toxicological analysis of The spirits were analyzed using Hewlett-Packard (Palo Alto, CA) GC/MS system with HP 6890 gas chromatograph, an HP 5972 mass selective detector (MSD) and an HP 6890 automatic liquid sampler GC/MS; the pressure of the carrier gas helium was 6.0 bar and the split value with a ratio of 1:100. The injection unit temperature set to 250 °C and MS quadrupole temperature set to 280 °C. The MS quadrupole detector ionization energy set to 70 eV. The initial column temperature was 60 °C (for 4 min) programmed by 6 °C/min to final temperature 160 °C and kept for 8 min at 160 °C. Utilized whisky and bogma raki samples were analyzed for the amounts of trans-anethole, ethanol, methanol, 1-propanolol, butanol, 2-butanol, 2-methyl-1-propanolol (isobutanol) and 3-methylbutanol (isoamyl alcohol). Histopathological changes in liver tissues were graded as follows; normal = 0 (<10%), mild = 1 (10%-40%), moderate = 2 (40%-70%), severe = 3 (above 70%). RESULTS: Chemical composition of illegally produced raki sample (%v/v) was as follows: trans-anethole %1.93, ethanol %95.70, 2-methyl-1-propanolol (isobutanol) %0.19, asetic acid %0.25, 3-methylbutanol (isoamyl alcohol) %0.77, and others %1.16. Chemical composition of commercial whisky sample (%v/v) was as follows: ethanol %97.72, 2-methyl-1-propanolol (isobutanol) %0.57, asetic acid %0.23, 3-methylbutanol (isoamyl alcohol) %1.28, and others %0.2. No traces of trans-anethole were detected in whisky. Normal liver morphology was recorded in control and walnut groups. However, bogma raki caused significant congestion and inflammatory cell infiltration compared to control and walnut group. On the other hand, whisky administration caused mild degeneration including inflammation in a limited area. CONCLUSION: Obtained findings suggest that trans-anethole containing alcoholic beverages are more hepatotoxic compared to commercial alcoholic beverages.