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David S Cassarino

Publications and source records attributed to David S Cassarino.

16 recordsLinked to original sources
PubMed2006

Distinction of benign sebaceous proliferations from sebaceous carcinomas by immunohistochemistry.

Sebaceous lesions, including sebaceous hyperplasia, sebaceomas, and sebaceous adenomas and carcinomas, are histologically distinctive adnexal proliferations with a spectrum of biological behavior ranging from benign to frankly malignant. The histologic distinction between sebaceous adenomas and carcinomas may be challenging, especially in cases showing atypical features and in small or partial biopsies. We studied multiple oncogenic and therapeutic related proteins by immunohistochemistry to identify differences in expression between benign and malignant sebaceous proliferations. A total of 27 cases, including 9 sebaceous adenomas, 4 sebaceomas, 8 sebaceous carcinomas, and 6 cases of sebaceous hyperplasia, were examined by immunohistochemistry, with antibodies directed against Ki-67 (MIB-1), bcl-2, p53, p21WAF1, p27Kip1, c-erbB-2 (Her-2/neu), CD117 (c-kit), cyclin D1, MDM2, CD99, MLH-1, and MSH-2. We found that sebaceous adenomas and sebaceomas stained like sebaceous hyperplasia did, whereas carcinomas had statistically significantly increased levels of p53 (50% versus 11%, respectively) and Ki-67 (30% versus 10%). The carcinomas also had significantly reduced levels of bcl-2 (7% versus 56%, respectively) and p21 (16% versus 34%) compared to the adenomas. Thus, a combination of several of these markers may be diagnostically useful in challenging cases. In addition, we found little or no Her-2/neu and CD117 staining, indicating that immunotherapy with Herceptin or Gleevac would likely not be useful for sebaceous carcinomas. Moreover, these results show that sebaceous adenomas and carcinomas are distinct neoplasms and provide no support for the theory that all sebaceous adenomas are truly malignant.

Adenocarcinoma, Sebaceous↗
PubMed2006

The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients.

BACKGROUND: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. DESIGN: We studied biopsies of 'clinically atypical' nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). RESULTS: Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. DISCUSSION: The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes.

Adult↗
PubMed2006

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two.

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.

Carcinoma, Squamous Cell↗
PubMed2006

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one.

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.

Carcinoma, Squamous Cell↗
PubMed2005

The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation.

Constitutive activation of Akt characterizes a high percentage of human melanomas and represents a poor prognostic factor of the disease. We show that Akt transforms melanocytes only in a hypoxic environment, which is found in normal skin. The synergy between Akt and hypoxia is HIF1alpha mediated. Inhibition of HIF1alpha decreases Akt transformation capacity in hypoxia and tumor growth in vivo, while overexpression of HIF1alpha allows anchorage-independent growth in normoxia and development of more aggressive tumors. Finally, we show that mTOR activity is necessary to maintain the transformed phenotype by sustaining HIF1alpha activity. Taken together, these findings demonstrate that Akt hyperactivation and HIF1alpha induction by normally occurring hypoxia in the skin significantly contribute to melanoma development.

Animals↗
PubMed2005

Primary cutaneous myxofibrosarcoma mimicking pleomorphic hyalinizing angiectatic tumor (PHAT): a potential diagnostic pitfall.

Myxofibrosarcoma (MFS) is one of the most common sarcomas of adults, and includes lesions ranging from low to high grade based on increasing cellularity, nuclear pleomorphism, and mitotic activity. We present an unusual case of MFS, which initially showed features of a pleomorphic hyalinizing angiectatic tumor (PHAT), a rare soft-tissue tumor considered benign in the WHO classification. The initial lesion showed a subcutaneous proliferation of spindled to polygonal eosinophilic cells with striking cellular pleomorphism, set in a myxoid to sclerotic stroma with prominent hyalinized and angiectatic vasculature, classic characteristics of PHAT. Rare mitotic figures were identified. The preliminary diagnosis of PHAT was confirmed by a consultant expert soft-tissue pathologist. Four months after the initial surgery, local recurrence was noted. The recurrent tumor demonstrated findings of a high-grade MFS, with a diffuse and cellular proliferation of atypical spindle cells set in a prominent myxoid stroma. Multiple mitoses, including atypical ones, were present. In light of these findings, the original specimen was reexamined and the initial diagnosis was amended to MFS. MFS may mimic or be confused with several benign soft-tissue lesions. Cases mimicking PHAT have not been previously reported. We describe a unique case of a high-grade MFS that initially showed characteristic features of a PHAT, to illuminate the fact that MFS may rarely arise in, or have areas that masquerade as, PHAT. It is also conceivable, although speculative, that at least some cases of PHAT, currently considered a benign tumor by the WHO, may actually represent or evolve into a unique form of MFS of low malignant potential.

Aged↗
PubMed2004

Spinal adrenal cortical adenoma with oncocytic features: report of the first intramedullary case and review of the literature.

Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent surgical intervention. A well-circumscribed, approximately 3 x 2 cm, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS.

Adrenal Cortex Neoplasms↗
PubMed2003

Widely invasive solitary fibrous tumor of the sphenoid sinus, cavernous sinus, and pituitary fossa.

Solitary fibrous tumor is a spindle cell tumor first described in the pleura, but also found in multiple extrathoracic sites including the meninges, orbit, nasal and paranasal sinuses. No cases have been previously reported in the cavernous sinus or pituitary fossa. We present the case of a 54-year-old woman who presented with progressive amaurosis. On imaging studies, a widely infiltrative lesion involving the pituitary fossa, sphenoid sinus, cavernous sinus, carotid artery, medial temporal, ethmoid, and pterygoid bones, and extending into the nasopharynx was discovered; impression was a malignant tumor originating in the pituitary fossa. At surgery, the tumor was only partially resectable because of extensive bony invasion and encasement of the carotid artery, and was found to compress but not invade the pituitary gland. Histology showed a spindle cell proliferation with a dense, hyalinized collagenous stroma and dilated vascular spaces, some showing a staghorn-like appearance. Areas of cellular pleomorphism and increased cellularity were present, but few mitoses were identified. Immunohistochemistry showed strong positivity with CD34, factor XIIIa, CD99, and Bcl-2. There was scattered cyclin D1, mib-1, and p53 positivity. Muscle, epithelial, vascular, and melanocytic markers were negative. These results led to the diagnosis of solitary fibrous tumor. The size, extensive invasion, and bony destruction indicated a tumor with at least low malignant potential. The occurrence of solitary fibrous tumors in the pituitary fossa and sinuses of the head and neck is rare, but must be considered in the differential diagnosis of spindle cell lesions in these regions.

Biomarkers, Tumor↗
PubMed2003

Widespread cutaneous and perioral metastases of mesothelioma.

BACKGROUND: Cutaneous involvement by mesothelioma represents a rare occurrence from an uncommon neoplasm. Most cases have resulted from local extension of an underlying body cavity mesothelioma or from surgical site contamination. We could only find six previously reported cases of distant cutaneous metastases of mesothelioma. METHODS: We describe a case of metastatic mesothelioma involving multiple skin sites and the lip in a 64-year-old man with an underlying primary pleural mesothelioma. RESULTS: A 64-year-old man presented with a lip lesion clinically diagnosed as keratoacanthoma vs. squamous cell carcinoma. Evaluation of the lip biopsy revealed tubulo-glandular and acinar-like arrangements of plump epithelioid cells with a hobnailed appearance, vesicular nuclei, and prominent nucleoli. The initial impression of metastatic carcinoma was revised to probable mesothelioma upon discovery of a previous history of pleural mesothelioma. Positive immunohistochemical stains for anti-cytokeratin, anti-calretinin, and HBME-1 and negative stains for anti-CEA, Leu-M1, B72.3, and Ber-Ep4 confirmed the diagnosis. CONCLUSION: We report a rare example of multiple cutaneous metastases of mesothelioma. We also demonstrate the usefulness of relatively new and specific immunomarkers for mesothelioma vs. adenocarcinoma. Metastatic mesothelioma to the skin or lip is a very rare occurrence but should be considered in the differential diagnosis of malignant epithelioid neoplasms.

Aged↗
PubMed2003

Metastatic nevoid melanoma in a 4 1/2-year-old child.

BACKGROUND: Childhood melanoma is a rare and controversial diagnosis. METHODS: We present the case of a 4 1/2-year-old child found to have an expanding, elevated pigmented lesion on her back. RESULTS: The biopsy showed a symmetrical, well circumscribed lesion. However, higher magnification revealed sheets of nevoid cells infiltrating deep into the dermis, lacking maturation, and exhibiting a high mitotic rate (average 5/10 high-power field) with deep mitoses. The possibility of nevoid melanoma was raised, and re-excision and sentinel lymph node (SLN) biopsy were recommended. Two SLNs were positive for melanoma, verified by immunohistochemical staining. In order to further characterize this melanoma, we performed immunohistochemistry for the tumor-suppressor p53, proliferation marker MIB-1, and oncogenes Bcl-2, cyclin D-1, and MDM-2. Staining for p53 was diffusely positive in the primary and the metastasis; MIB-1 showed moderate proliferative rate in the primary (approximately 10%); Bcl-2 was weakly positive in the primary and showed focal staining in the metastasis; cyclin D-1 was strongly positive in the primary and metastasis; and MDM-2 staining showed scattered positive cells in both lesions. CONCLUSIONS: These findings are consistent with a metastatic nevoid melanoma arising in the absence of predisposing disease in a young child, a distinctly unusual occurrence.

Back↗
PubMed2003

Lyme-associated parkinsonism: a neuropathologic case study and review of the literature.

Neurological complications of Lyme disease include meningitis, encephalitis, dementia, and, rarely, parkinsonism. We present a case of striatonigral degeneration, a form of multiple system atrophy, in Lyme-associated parkinsonism. A 63-year-old man presented with erythema migrans rash, joint pains, and tremors. Serum and cerebrospinal fluid antibodies and polymerase chain reaction for Borrelia burgdorferi were positive. Clinical parkinsonism was diagnosed by several neurologists. Despite treatment, the patient continued to decline, with progressive disability, cognitive dysfunction, rigidity, and pulmonary failure. At autopsy, the brain showed mild basal ganglia atrophy and substantia nigra depigmentation, with extensive striatal and substantia nigral neuronal loss and astrogliosis. No Lewy bodies were identified; however, ubiquitin-positive glial cytoplasmic inclusions were identified in striatal and nigral oligodendroglia. There were no perivascular or meningeal infiltrates, the classic findings of neuroborreliosis. To our knowledge, this is the first report of striatonigral degeneration in a patient with B burgdorferi infection of the central nervous system and clinical Lyme-associated parkinsonism.

Antibodies, Bacterial↗
PubMed2002

Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma.

Cell models of neurodegenerative diseases (NDD) can involve expression of mutant nuclear genes associated with Mendelian forms of the diseases or effects of toxins believed to replicate essential disease features. Death produced by exposing neural cells to methylpyridinium ion (MPP(+)) or neurotoxic beta amyloid (BA) peptides is frequently used to study features of the sporadic, most prevalent forms of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. We examined in replicating SH-SY5Y human neuroblastoma cells the release of cytochrome C into cytoplasm, activation of caspases 9 and 3, and loss of calcein retention as markers of the "mitochondrial" pathway of cell death. Exposure to 5 mM MPP(+), which induces apoptotic cell death within 18-24 hr, released cytochrome C within 4 hr, activated caspases 9 and 3, and reduced calcein accumulation. BA 25-35 peptide produced more rapid and greater elevations of caspase 3 activity; no effects were observed with the nontoxic BA 35-25 reverse sequence. The dependence on mitochondrial transition pore (MTP) activity of MPP(+)-induced caspase activations was demonstrated by preincubation with bongkreckic acid, which blocked elevations of caspases 9 and 3. Stereoisomers of pramipexole (PPX), a free radical scavenger and inhibitor of MTP opening, inhibited caspase activation (MPP(+) and BA) and restored calcein accumulation (MPP(+)). Our results demonstrate that MPP(+) and BA can induce cell death through MTP-dependent activation of caspase cascades. PPX stereoisomers interfere with activation of these cell death pathways and may be useful clinically as neuroprotectants in PD and AD and related diseases.

1-Methyl-4-phenylpyridinium↗