Walter L. Rush

Survival Analysis of 200 Pulmonary Neuroendocrine Tumors With Clarification of Criteria for Atypical Carcinoid and Its Separation From Typical Carcinoid

Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade categories of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). We studied 200 neuroendocrine lung tumors to critically evaluate the Arrigoni histologic criteria for AC using statistical analysis to delimit more rigorously an intermediate survival for AC between TC and the high-grade tumors of LCNEC and SCLC. Histologic features that might predict prognosis were used for Kaplan-Meier and Cox proportional hazards survival analysis, and an optimal mitotic range for AC was calculated. The optimal mitotic range for AC was 2 to 10 mitoses per 2 mm2 of viable tumor (10 high-power fields). Based on this finding, we collapsed mitoses into three categories (< 2; 2-10; > or = 11) and performed Cox multivariate analysis for all 200 neuroendocrine tumors. Mitotic counts were the only independent predictor of prognosis. Based on this analysis, we propose that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis. Using these criteria, the 200 neuroendocrine tumors were classified as 51 TC, 62 AC, 37 LCNEC, and 50 SCLC. The 5- and 10-year survival was 87% and 87% for TC, 56% and 35% for AC, 27% and 9% for LCNEC, and 9% and 5% for SCLC, respectively. After stratification for stage, survival for AC was significantly worse than for TC (p < 0.001); for LCNEC and SCLC it was significantly worse than for AC; but the survival for LCNEC was no different than that for SCLC.

Neonatal sunburn and melanoma in mice.

Retrospective epidemiological data have indicated that cutaneous malignant melanoma may arise as a consequence of intense, intermittent exposure of the skin to ultraviolet radiation, particularly in children, rather than from the cumulative lifetime exposure that is associated with other forms of skin cancer. Here we use a genetically engineered mouse model to show that a single dose of burning ultraviolet radiation to neonates, but not adults, is necessary and sufficient to induce tumours with high penetrance which are reminiscent of human melanoma. Our results provide experimental support for epidemiological evidence that childhood sunburn poses a significant risk of developing this potentially fatal disease.

Pulmonary Pathology of Erdheim-Chester Disease

Erdheim-Chester disease (ECD) is a rare non-Langerhans’ cell histiocytosis that may present with pulmonary symptoms. The condition seems to be nonfamilial and typically affects middle-aged adults. Radiographic and pathologic changes in the long bones are diagnostic, but patients often present with extraskeletal manifestations. Advanced pulmonary lesions are associated with extensive fibrosis that may lead to cardiorespiratory failure. The clinical, radiologic, and pathologic features of six patients with ECD with lung involvement are presented. The patients were three men and three women (mean age, 57). Five presented with progressive dyspnea, and one presented with diabetes insipidus. Open-lung biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated fibrosis and lymphoplasmacytic inflammatory infiltrates. The histiocytes did not stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens from five of six patients showed that the histiocytes were positive for CD68 and Factor XIIIa and negative for CD1a. Specimens from two patients exhibited immunoreactivity for S-100 protein. Electron microscopy studies performed on specimens from two patients showed phagocytic lysosomes but no Birbeck granules. Clinical follow-up of up to 16 years was available. At the end of that time, five patients were dead of complications related to their disease; one patient remains alive 4 years after diagnosis but with severe respiratory compromise. ECD is a rare non-Langerhans’ cell histiocytosis that may present as interstitial lung disease and resemble other pulmonary conditions, particularly usual interstitial pneumonitis and pulmonary Langerhans’ cell histiocytosis. Recognition of this entity will allow better assessment of its true incidence, therapeutic options, and prognosis.

Primary anaplastic large cell lymphoma of the lung: A clinicopathologic study of five patients

Primary anaplastic large-cell lymphoma is a rare malignancy in the lung. Anaplastic large-cell lymphoma characteristically involves the lymph nodes or skin, with few reports from other sites. We studied the clinical and pathologic features of five cases of anaplastic large-cell lymphoma limited to the lungs. The patients were three women and two men aged 27 to 66 years (mean, 44.6 y) The tumors ranged in size from 1.1 to 5 cm. All patients were CD 30 (Ki-1) positive and CD 15 (LeuM-1) negative. Epithelial membrane antigen immunoreactivity was seen in two patients. Epstein-Barr virus was not detected by immunohistochemistry (four patients tested) or by polymerase chain reaction studies (three patients tested). The immunophenotypes were T cell (n = 3) and null (n = 2). Gene rearrangement studies supported the immunophenotypic findings. One patient who had underlying HIV infection died of infectious complications. One patient died at 6 months. Two patients developed recurrent disease and are alive after 42 and 51 months of follow-up. The remaining patient is alive at 8 years of follow-up without evidence of disease. ALCL can mimic metastatic or primary carcinoma and should be considered in the differential diagnosis of large cell neoplasms of the lung.

Primary intrapulmonary meningiomas : A clinicopathologic and immunohistochemical study of ten cases

Primary intrapulmonary meningiomas are rare, and their occurrence has been reported in the literature only sporadically.

Hepatocellular carcinoma presenting as a precocious cutaneous metastasis

The authors report a case of hepatocellular carcinoma (HCC) diagnosed by evaluation of a cutaneous metastasis in a patient without a prior diagnosis of HCC. Subsequent evaluation confirmed the presence of additional widespread metastatic disease. The medical literature is reviewed with regards to cutaneous metastasis, including precocious metastasis, of HCC. The pathologic evaluation of HCC is reviewed, including a discussion of the immunohistochemical profile of this malignancy and the utility of hepatocyte paraffin 1, CD10, and polyclonal carcinoembryonic antigen (pCEA) immunohistochemical stains.

Pure apocrine nevus: A report of 4 cases

Abstract: Apocrine nevus is a rare tumor composed of increased mature apocrine glands and ductal structures within a fibrous stroma, located predominantly in the reticular dermis. They have been reported in association with apocrine carcinoma, extramammary Paget disease, and syringocystadenoma papilliferum; less commonly a pure apocrine nevus is identified, unassociated with another apocrine proliferation. Clinically apocrine nevi may appear as solitary or multiple nodules or plaques on the scalp, presternal skin, though they are seen most commonly in the axillae. We describe 4 cases of pure apocrine nevus, all of which appeared clinically as painless or mildly tender skin-colored axillary masses, 2 of which were bilateral. In each case, the lesions appeared in adulthood, and patients denied knowledge of congenital or childhood presence. Patients denied pruritis, discharge, bleeding, or antecedent trauma. Grossly, the specimens consisted of subcutaneous, multicystic ill-defined nodules. Biopsy showed prominent apocrine glands composed of irregularly columnar luminal cells with eosinophilic cytoplasm arranged in a somewhat organoid pattern filling the reticular dermis and extending into the subcutaneous adipose tissue. The glandular luminal cells displayed decapitation secretion. There was a paucity of pilosebaceous units. In one case, the overlying epidermis was papillomatous. The deepest portion of one specimen had lactational change simulating a lactational adenoma. No atypia was seen in either the glandular structures or the stroma. The adjacent sebaceous and eccrine structures were normal. The histologic features and immunohistochemical profile in relation to other apocrine lesions will be reviewed.

Cutaneous involvement in the lymphoepithelioid variant of peripheral T-cell lymphoma, unspecified (Lennert lymphoma). Report of a case and review of the literature

Lennert lymphoma (LL), or the lymphoepithelioid variant of peripheral T‐cell lymphoma, is an uncommon entity with rarely seen or reported presentations in the skin. Cutaneous involvement of LL has been characterized by asymptomatic, non‐ulcerated, red to violet papules, nodules and small plaques (less than 5 cm) on the trunk and extremities. Histologically, there are localized cellular lymphoid infiltrates in the dermis that tend to localize around blood vessels or skin appendages. Key to the diagnosis of LL is the presence of epithelioid histiocytes and atypical small lymphoid cells without increased vascularity or epidermotropism. Immunophenotyping shows a dense monoclonal T‐cell population commonly associated with aberrant loss of T‐cell‐associated antigens. T‐cell receptor gene rearrangements are also identified. Patients typically present with advanced stage and have a low 5‐year survival. Herein, we present a case of cutaneous involvement by LL at the time of initial presentation that persisted after initiation of chemotherapy and was finally verified as secondary cutaneous involvement of LL 1 year later histologically, immunophenotypically and by T‐cell receptor gene rearrangement studies.

Granular cell basal cell carcinoma: report of a case and review of the literature.

Abstract:Granular cell basal cell carcinoma (BCC), characterized by large cells with abundant eosinophilic cytoplasm and conspicuous granularity, is an extremely rare variant of BCC with only 14 cases reported in the literature to date. A case of an 82-year-old man with clinically suspected BCC of the face is presented. Microscopic examination demonstrated characteristic morphologic and immunophenotypic features of granular cell BCC, as well as novel expression of p16 and lack of bcl-2 expression, both of which are previously undescribed in granular BCCs in the literature to date. Although very rare, this entity is important to include in the differential of any nodular cutaneous neoplasm with granular features. The rarity of this lesion makes immunohistochemistry especially helpful. As in other BCCs, granular cell BCCs typically strongly express Ber-EP4 and cytokeratins. The granular BCCs are characteristically periodic acid–Schiff positive, but show no expression of S100 protein. The rarity of the granular cell BCC and the aggressive biological behavior of the entities that may share similar histologic features make arriving at the correct diagnosis paramount to appropriate clinical management. The fifteenth case of granular cell BCC with subsequent review of the literature is reported, with particular focus on the immunohistochemical characteristics.

Deep Penetrating Fibrous Histiocytoma: A Case Report and Implications for Surgical Management.

Deep penetrating fibrous histiocytoma (DPFH) is a rare variant of fibrous histiocytoma that can arise in the subcutis and deep soft tissues with different clinical implications from dermatofibromas. Dermatofibromas are mainly cosmetic annoyances and do not require surgical management. However, the DPFH does require that negative surgical margins be achieved because of the possibility of local recurrence and distant metastasis. We describe a case of a 24-year-old man diagnosed with DPFH through histologic examination and immunohistochemistry. The lesion displayed diffuse, strong D2-40 positivity and a minority of cells were highlighted with factor XIIIa. The lesion was negative for CD34. The patients lesion was incompletely excised and a repeat excision was required.