EGFR and K-ras gene mutation status in squamous cell anal carcinoma: a role for concurrent radiation and EGFR inhibitors?

BACKGROUND: There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N. METHODS: Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis. RESULTS: The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19. CONCLUSION: The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.

Paraganglioma of the tongue.

Paragangliomas are neuroendocrine tumors arising from extra-adrenal autonomic ganglia. We present what is to our knowledge the first immunohistochemically documented case of a paraganglioma of the tongue, a 2.5-cm benign tumor growing in the position of the foramen cecum. The patient was an elderly woman who presented with throat irritation. The histologic profile and ultrastructural appearance of this lesion were classic for paraganglioma, and cells stained strongly for neurosecretory granules by immunohistochemistry. Carcinoid, ectopic thyroid neoplasm, and other tumors that mimic paraganglioma were ruled out on immunohistochemical grounds. To our knowledge, paraganglia have not been previously documented in the tongue; this tumor may have arisen from a branch of cranial nerve VII or IX, or from an embryologic remnant of the thyroid or thyroid capsule.

Schnyder's crystalline corneal dystrophy in association with hyperlipoproteinemia: histopathological and ultrastructural findings.

A 61-year-old man with Schnyder's crystalline corneal dystrophy showed a slight reduction in vision during 16 years of observation. Plasma lipoprotein analysis done 10 years after presentation showed type IIA hyperlipoproteinemia, which was also detected in one of four siblings examined, none of whom showed the characteristic corneal dystrophy. Electron microscopic studies on corneal biopsy specimens from the patient showed abundant crystalline material and vacuoles predominantly in the superficial corneal stroma, with occasional keratocytes and rare basal epithelial cells containing laminated structures. The findings of a focal continuity between the trilaminar membrane around some of the stromal vacuoles and the plasmalemma of the keratocytes as well as dissolution of the plasmalemma in other keratocytes are consistent with the hypothesis of a local cellular role in the development of this corneal disorder.

Rhabdomyomatosis of newborn lung: a case report with immunohistochemical and electronmicroscopic characterization of striated muscle cells in the lung.

Interstitial proliferation of striated muscle cells in the lung is rare. A few cases in the literature only document infants with associated lung and other major organ anomalies incompatible with long-term survival. In this report we document a case of diffuse patchy interstitial proliferation of striated muscle cells in the left lung and confirm their nature by immunohistochemistry and electron microscopy. In particular, we show that these skeletal muscle cells express alpha-sarcomeric actin, but not alpha-smooth muscle actin, indicating an antigenetically well-developed striated muscle phenotype despite morphologically embryonal features.

Renal oncocytoma in pregnancy: a case report.

Oncocytoma is an uncommon renal tumour and this is the first report of such a tumour occurring in a pregnant woman. Optimal treatment is nephrectomy and the prognosis is usually good, though metastasis has been reported. It is unknown whether pregnancy alters tumour behaviour or the prognosis.

A case of perianal mucinous adenocarcinoma arising in a fistula-in-ano. A clue to the early pathologic diagnosis.

The author presents a case of perianal mucinous adenocarcinoma supervening on a long-standing fistula-in-ano. Features of this unusual neoplasm are reviewed. This case is of particular interest because a review of surgical material from a fistulotomy performed two years before the diagnosis of adenocarcinoma provides a clue to the early diagnosis. The clue is the presence of globules of mucin present in the granulation tissue and free on the slide. Fifty routine fistulotomy or fistulectomy specimens did not contain mucin globules. Recognition of the appearance of these mucin globules in fistulectomy or fistulotomy specimens can alert the pathologist to the possibility of perianal mucinous adenocarcinoma, resulting in earlier diagnosis and treatment.

Ultrastructural markers of lymph nodes in patients with acquired immune deficiency syndrome and in homosexual males with unexplained persistent lymphadenopathy. A quantitative study.

To determine if vesicular rosettes (VR), tubuloreticular structures (TRS), and "test-tube and ring-shaped forms" (TRF) are characteristic ultrastructural features of the syndromes of acquired immune deficiency (AIDS) or of unexplained persistent lymphadenopathy (PLS), the authors studied lymph nodes from nine patients with PLS, two patients with AIDS, and seven controls by electron microscopy. An average of 122 lymphocytes per case were photographed. VR were present in only 0.37% of lymphocytes in 4 of 11 index cases and were mimicked by grouped vesicles and degenerating multivesicular bodies (MVB). TRS were found in 10 of 11 index cases, compared with only one of seven controls (P less than 0.01). In the index cases, they were more frequent in AIDS (mean 21%) than in PLS lymphocytes (mean 4%) (P less than 0.05). MVB were found in all index cases and five of seven controls and were more frequent in index lymphocytes (mean 19%) than in controls (mean 5%) (P less than 0.01). TRF were found in one Haitian male with AIDS, where they were present in 4% of lymphocytes. VR are infrequent and indistinct. MVB probably reflect the reactivity of the lymphocytes. TRF is not a feature of PLS. The authors conclude that there are no pathognomonic ultrastructural markers of AIDS or PLS but that TRS are characteristic of both syndromes and occur frequently enough to be supportive to the diagnosis of AIDS and PLS.

Renal involvement in malignant histiocytosis. An immunoperoxidase marker study.

In two patients who had malignant histiocytosis, renal involvement was present at an early stage of their diseases and consisted clinically of proteinuria and renal failure. The associated renal lesion was characterized by a diffuse and global endocapillary hypercellularity of the glomeruli imputable to atypical cells occluding the capillary loops. Immunoglobulins were absent from this lesion. The atypical cells were positively identified by lysozyme immunoperoxidase study as malignant histiocytes. It is suggested that renal biopsy complemented by marker study could play a role in the diagnosis of malignant histiocytosis.