NK cell enteropathy: a case report with 10 years of indolent clinical behaviour.

AIMS: Natural killer (NK) cell enteropathy is a recently described clinically indolent condition characterised by atypical NK cell infiltrates in the gastrointestinal mucosa that mimics malignant lymphoma. We report a case that highlights the indolent clinical behaviour by documenting absence of clinical progression over 10 years. METHODS AND RESULTS: We report the case of a 69-year old female who had clinically long-standing abdominal pain and recurrent mucosal ulcerations associated with atypical NK cell infiltrates. The clinical, morphologic and immunophenotypical findings in this case were diagnostic of NK cell enteropathy. Review of the patient's prior biopsies demonstrated that this persisted without clinical progression for 10 years, confirming the clinical indolent course. CONCLUSION: Recognition of NK cell enteropathy is important to avoid over-diagnosing this benign condition as an aggressive lymphoma.

IMAGe association: report of two cases in siblings with adrenal hypoplasia and review of the literature.

We report the postmortem findings of two siblings with gross and microscopic features consistent with IMAGe association (Intrauterine growth retardation, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies) with an emphasis on the histopathology of the adrenal gland in this rare syndrome. The first sibling was an 8-week old male diagnosed postnatally with primary adrenal insufficiency. There was no deletion of the DAX1 gene by FISH. Examination at autopsy revealed dysmorphic features including frontal bossing, epicanthal folds, flat philtrum, cryptorchidism, penile chordee, overriding fourth toe, and height and weight below 3rd percentile. Grossly, the adrenal glands were not identified; however, microscopic examination of the suprarenal soft tissue revealed a 3 mm focus of disorganized fetal adrenal cortex with distended "cytomegalic" cells with abundant pink eosinophilic cytoplasm, vesicular nuclei, and cytoplasmic vacuolization. A minute focus of permanent adult cortex was also seen, but no adrenal medulla was identified. An autopsy of the sibling, who died 12 years previously at day 9 of life, revealed dysmorphic facial features with cryptorchidism and a large phallus. The adrenal glands were grossly hypoplastic (11 mm). Histologically, the adrenal glands showed disorganized fetal cortex with cytomegalic cells, a larger amount of permanent adult cortex, and bizarre nuclei with numerous pseudoinclusions. While there is currently limited information regarding the histopathologic adrenal findings in IMAGe association, our small case series suggests overlapping features between X-linked recessive congenital adrenal hypoplasia (cytomegalic cells with lack of permanent adult cortex) and autosomal recessive congenital adrenal hypoplasia (diminished permanent adult cortex without cytomegalic cells).

Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

Use of an endoscope-compatible probe to detect colonic dysplasia with Fourier transform infrared spectroscopy.

Fourier transform infrared (FTIR) spectroscopy is sensitive to the molecular composition of tissue and has the potential to identify premalignant tissue (dysplasia) as an adjunct to endoscopy. We demonstrate collection of mid-infrared absorption spectra with a silver halide (AgCl(0.4)Br(0.6)) optical fiber and use spectral preprocessing to identify optimal subranges that classify colonic mucosa as normal, hyperplasia, or dysplasia. We collected spectra (n=83) in the 950 to 1800 cm(-1) regime on biopsy specimens obtained from human subjects (n=37). Subtle differences in the magnitude of the absorbance peaks at specific wave numbers were observed. The best double binary algorithm for distinguishing normal-versus-dysplasia and hyperplasia-versus-dysplasia was determined from an exhaustive search of spectral intervals and preprocessing techniques. Partial least squares discriminant analysis was used to classify the spectra using a leave-one-subject-out cross-validation strategy. The results were compared with histology reviewed independently by two gastrointestinal pathologists. The optimal thresholds identified resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively. These results indicated that mid-infrared absorption spectra collected remotely with an optical fiber can be used to identify colonic dysplasia with high accuracy, suggesting that continued development of this technique for the early detection of cancer is promising.

Placental site trophoblastic tumor in the ovary of a young child with isosexual precocious puberty.

The authors report a unique case of a primary ovarian placental site trophoblastic tumor (PSTT) in a 30-month-old girl who presented with isosexual precocious puberty of 1 month duration. Laboratory studies revealed mildly elevated beta human chorionic gonadotropin (37.5 mIU/ml; reference range <3.0 mIU/ml) and estradiol (74 pg/ml; reference range 0 to 56 pg/ml) serum levels. A 3.5-cm right ovarian mass was detected radiographically. The tumor was confined to the ovary as proven by the preoperative staging workup and the exploratory laparotomy. Microscopically, it was composed of intermediate trophoblastic cells with angioinvasive growth and deposition of fibrinoid material. The tumor cells were diffusely positive for human leukocyte antigen G, melanoma cell adhesion molecule (CD146), and cytokeratins (AE1/AE3, CK18, and CAM 5.2). Stains for human chorionic gonadotropin, alpha-inhibin, and human placental lactogen showed focal immunoreactivity. Serum markers returned to normal postoperatively. The patient remains disease-free at 24-months follow-up. We propose that tumors morphologically identical to uterine PSTT may rarely occur as gonadal germ cell tumors in children.

Laparoscopic resection of a virilizing adrenocortical tumor.

Virilizing adrenocortical tumors are rare. Laparoscopic unilateral adrenalectomy with serum androgen surveillance may provide curative treatment for benign, functional adenomas. Herein, we describe a case of laparoscopic resection of a testosterone-producing adrenal tumor in a sixteen-year-old female.