Muscle invasion in oral tongue squamous cell carcinoma as a predictor of nodal status and local recurrence: just as effective as depth of invasion?

Tumor depth of invasion (DOI) is a histologic feature that consistently correlates with lymph node metastasis; however, there are many difficulties with accurately assessing DOI. The aim of this study was to identify a simpler and more reproducible method of determining DOI, by using skeletal muscle invasion as a surrogate marker of depth. Oral tongue squamous cell carcinoma American Joint Committee on Cancer (AJCC) stage T1 cases were identified in the Emory University Department of Pathology database. 61 cases, with a minimum of 2 years of follow-up, were included in the study. Cases were examined histologically to assess muscle invasion and DOI. The two methods of measurement were analyzed to determine the positive predictive value (PPV) of DOI or muscle invasion for both nodal disease and local recurrence. Cases with muscle invasion had a 23.3% PPV of occult lymph node metastasis. Cases with DOI of greater than 3 mm had a 29.7% PPV of occult lymph node metastasis. Cases with muscle invasion had a 43.7% PPV of local tumor recurrence. Cases with maximum DOI of greater than 3 mm had a 40.4% PPV of tumor recurrence. Although the PPV of muscle invasion in regards to nodal status was slightly less than DOI, it represents a more easily reproducible parameter which could guide surgeons in determining if the case warrants an elective neck dissection in a cN0 (clinically negative) neck. Interestingly, the PPV of local recurrence was higher with muscle invasion than DOI, and may represent an important indicator for extent of resection.

An uncommon case of de novo CD10+ CD5- mantle cell lymphoma mimics follicle center B cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by expression of CD5, overexpression of Cyclin D1 as a result of chromosomal translocation t(11;14)(q13;q32), and poor prognosis. Cases of MCL lacking CD5 expression as well as cases with coexpression of CD5 and CD10 have also been reported. Here we describe an uncommon case of de novo MCL with expression of CD10, but not CD5, mimicking lymphoma of germinal center-derived B cells. The lymphoma cells in this case demonstrated a diffuse pattern of proliferation, and were strongly positive for Cyclin D1 by immunohistochemical stain. Fluorescence in situ hybridization studies demonstrated the presence of t(11;14)(q13;q32) involving BCL1, but not chromosomal translocations involving C-MYC or BCL2, confirming the diagnosis of MCL. This case further highlights the importance of comprehensive immunophenotypic and genetic characterization in the diagnosis and classification of B-cell lymphomas.

T-cell receptor gene rearrangement and CD30 immunoreactivity in traumatic ulcerative granuloma with stromal eosinophilia of the oral cavity.

Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an ulcerative lesion of the oral mucosa with unknown pathogenesis. A few recent case reports have demonstrated molecular evidence of T-cell clonality in TUGSE and CD30 immunoreactivity in the large atypical mononuclear cells, raising the possibility that a TUGSE subset may represent the oral counterpart of primary cutaneous CD30+ T-cell lymphoproliferative disorders. We examined the immunoreactivity for CD30 and T-cell receptor (TCR) gamma gene rearrangement in 37 TUGSE cases. Clonal TCR gene rearrangements were demonstrated in 7 (24%) of 29 cases with amplifiable DNA, and the morphologic features and CD30 immunoreactivity of these cases did not differ from those with polyclonal TCR gene rearrangements. Clinical follow-up was available for 5 of 7 TUGSE cases with clonal TCR gene rearrangement for an average period of 1.75 years after the initial biopsy or excision, and there was no evidence of local recurrence or development of systemic T-cell lymphoproliferative disorder. Without morphologic and/or clinical evidence of lymphoma, T-cell clonality and/or CD30 positivity in these lesions is not indicative of malignancy and should be interpreted with caution.

Rhabdomyosarcoma of the maxillary gingiva.

BACKGROUND: Rhabdomyosarcoma is a malignant neoplasm of primitive mesenchyme exhibiting skeletal muscle differentiation. Oral rhabdomyosarcoma is rare and accounts for only 0.04% of all head and neck malignancies. METHODS: A 33-year-old woman presented with an erythematous gingival mass involving the anterior maxillary gingiva. The lesion had been present for > or =13 months before presentation, and in recent months, it had become intermittently painful. RESULTS: Clinical examination exhibited erythema and enlargement of the interdental papillae between the left maxillary canine, lateral incisor, and central incisor. The tissue was boggy and tender on palpation. Incisional biopsies were performed, and microscopic examination showed a cellular proliferation of spindle-shaped to ovoid cells with hyperchromatic, enlarged, and pleomorphic nuclei. Many of the tumor cells exhibited abundant eosinophilic cytoplasm. Immunohistochemical stains showed the tumor cells to be positive for desmin, myogenin, and myogenic differentiation 1 (MyoD1). A diagnosis of embryonal rhabdomyosarcoma was made. The patient was treated by surgical resection with postoperative chemotherapy and radiation. The patient had no evidence of disease at a follow-up examination 1 month after completion of therapy. CONCLUSIONS: Oral rhabdomyosarcoma can develop insidiously. Pain is a variable presenting symptom, and early lesions may be mistaken for benign neoplastic, inflammatory, or infectious processes. Over several decades, a multidisciplinary treatment approach that includes surgical removal if resectable, in combination with multiagent chemotherapy and possibly radiation therapy, has improved survival rates.

Inverted papilloma of the nasolacrimal system invading the orbit.

A 73-year-old man with a history of epiphora, discharge from the left eye, and left-sided nasal congestion underwent external dacryocystorhinostomy for nasolacrimal duct obstruction. The procedure revealed bony erosion of the majority of the lacrimal sac fossa and a large papillomatous mass filling the lacrimal sac and nasolacrimal duct. Inverted papilloma was diagnosed via biopsy. A subsequent orbitotomy with combined endoscopic medial maxillectomy was performed to remove the mass. This case illustrates the importance of including inverted papilloma, a benign but invasive neoplasm, in the differential diagnosis of nasolacrimal duct obstruction.

Immunohistochemical detection of p16INK4a in dysplastic lesions of the oral cavity.

Significant intra- and interobserver variability exists in diagnosing and grading oral epithelial dysplasia. Mutations in the tumor-suppressor gene p16 are common in oral cavity dysplastic lesions, but whether immunohistochemical detection of the gene product p16(INK4a) (p16) can be used as a reliable biomarker for dysplasia is unclear. In total, 119 biopsy specimens representing various oral cavity sites and degrees of dysplasia were retrieved from the pathology files of Emory University Hospital. Formalin-fixed, paraffin-embedded sections were stained with hematoxylin and eosin (H&E) and with a monoclonal antibody to p16 (LabVision Corporation, Clone JC2). A blinded review of the H&E slides and the pattern and degree of p16 expression was independently performed by two pathologists. A consensus was obtained when diagnoses differed. Morphologic diagnoses were then compared to p16 immunohistochemical expression. Overall, 61/119 (51%) cases showed no p16 immunoreactivity, including 12/33 (36%) cases of no dysplasia, 11/28 (39%) cases of mild dysplasia, and 38/58 (66%) cases of moderate/severe dysplasia. The remaining cases showed p16 expression limited to the basal and suprabasal nuclei and generally confined to the lower one-third of the epithelium. A logistic regression model showed a trend toward absent p16 expression with increasing severity of dysplasia (P=0.006). Decreased expression of p16 in dysplastic lesions, as found in this study, may reflect the biologic events involving loss of p16 gene function in the pathogenesis of oral cancer. Our findings suggest that p16 immunohistochemistry is not helpful in differentiating dysplastic from nondysplastic mucosa in oral cavity biopsies, and thus is not a reliable biomarker for use in routine clinical practice.

C-kit expression distinguishes salivary gland adenoid cystic carcinoma from polymorphous low-grade adenocarcinoma.

Adenoid cystic carcinoma (ACC) is characterized by persistent, relentless growth and a high rate of eventual metastasis. In contrast, polymorphous low-grade adenocarcinoma (PLGA) has a much lower risk of recurrence and rarely metastasizes. The histologic patterns of these two neoplasms can be similar. Expression of c-kit, a transmembrane receptor tyrosine kinase, has recently been reported to be expressed in ACC but not PLGA. Expression of galectin-3, a nonintegrin beta-galactosidase-binding lectin, has been reported to be significant in PLGA and decreased in ACC.Formalin-fixed paraffin-embedded tissue from 9 ACC and 14 PLGA were immunostained for c-kit and galectin-3. Cases were scored as 1+ (5-25% positive), 2+ (26-50% positive), or 3+ (>50% positive). C-kit was expressed by 100% of ACC (3+: 7 cases; 2+: 1 case; 1+: 1 case) and by 57% of PLGA (2+: 2 cases; 1+: 6 cases). In all but one ACC, c-kit expression was confined to the inner cell layer. C-kit expression was also noted in the intercalated duct epithelium of the salivary glands and the acinar cells of the lacrimal gland. Galectin-3 was expressed in 8 of 9 cases of ACC and 14 of 14 cases of PLGA. The results of this, the first study to compare c-kit and galectin-3 expression in ACC and PLGA, suggest that c-kit expression characterizes ACC, but not PLGA. Galectin-3 immunohistochemistry does not have a role in the differentiation of ACC and PLGA. C-kit immunostaining may be a valuable adjunctive tool for this differential diagnosis, particularly in the setting of a limited biopsy. Our finding of different patterns of c-kit expression in tubular and solid variants of ACC supports the concept of solid variant ACC as a high-grade tumor, with progression toward an entirely "inner cell" phenotype.