Collagenous myofibroblastic tumor of the mandible: case report of a unique locally aggressive neoplasm.

We report a locally aggressive collagenous myofibroblastic neoplasm of the mandible in an 18-year-old male. Clinically, the lesion presented with rapid growth and irregular mandibular bone destruction. Grossly, the tumor was 10 cm in greatest dimension, light-tan, firm, and involving the posterior one-thirds of the body and inferior half of the left mandibular ramus. Histologically, the lesion was composed of a loose spindle cell proliferation interspersed with periodic dense bands of collagen. The spindle cells reacted positively to smooth muscle actin, calponin, and focally to desmin and were negative for S-100, pan-cytokeratin, CD99, CD34 and caldesmon, supporting myofibroblastic derivation. At our 4 year follow-up, the patient remained free of local recurrence and surgery related complications. The clinicopathologic findings and the differential diagnosis of this lesion is presented and discussed.

Cutaneous adnexal tumor with an unusual presentation--discussion of a potential diagnostic pitfall.

The clinical presentation of skin adnexal tumors is nonspecific, and histologically; the differential diagnosis between primary cutaneous adnexal malignant carcinomas and metastatic tumors with a visceral origin can be challenging. We report a patient with history of invasive ductal carcinoma of the breast who presented with a 1-cm erythematous palpable lesion on her right calf. The biopsy showed an intradermal proliferation of malignant epithelioid cells with ductal differentiation, histologically compatible with metastatic breast carcinoma. However, the tumor cells labeled strongly and diffusely not only for pancytokeratin and cytokeratin (CK7) but also with p63 and CK5/6; carcinoembryonic antigen highlighted the ductal structures. No labeling was seen for mammoglobin, estrogen/progesterone, Her2-neu, S-100 protein, CK20, thyroid transcription factor-1 (TTF-1), and CDX-2. Based on the p63 and CK5/6 positivity, the differential diagnosis also included the possibility of a primary adnexal neoplasm and a complete excision was advised. The reexcision specimen revealed residual infiltrating dermal tumor and an overlying intraepithelial component with marked cytologic atypia and focal duct formation, diagnostic of a primary cutaneous adnexal tumor with ductal differentiation (porocarcinoma). Immunohistochemical studies (like p63 and CK5/6) can help to differentiate a primary cutaneous neoplasm from a metastatic lesion. This discrimination is of a paramount importance because a diagnostic error can result in profound implications for patient's assumed prognosis and subsequently applied therapy.

Adult Henoch-schönlein purpura in a patient with myelodysplastic syndrome and a history of follicular lymphoma.

GOAL: To understand Henoch-Schönlein purpura (HSP) to better manage patients with the condition. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the criteria for diagnosing HSP. 2. Explain the association of malignancy and HSP. 3. Discuss the prevalence of HSP in adults. Henoch-Schönlein purpura (HSP) is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract. In skin, it is associated with IgA deposition around dermal blood vessels. While an exact cause of HSP has not been elucidated, several processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. We present a 57-year-old woman with a history of follicular lymphoma who developed HSP likely associated with myelodysplastic syndrome. This case is clinically significant because the patient was thought to be in remission of her hematologic disease until her skin findings prompted further evaluation. Her diagnosis of HSP was based on clinical presentation with palpable purpura and abdominal pain, and was confirmed with biopsy and immunohistochemical analyses of purpuric papules demonstrating leukocytoclastic vasculitis and strong anti-IgA labeling in the dermal endothelial cells consistent with immunocomplex deposition. The occurrence of vasculitis and malignant disease in the same patient often is difficult to interpret, as some patients may exhibit both diseases independently and by chance, while others may have vasculitis as a paraneoplastic syndrome. We review cases of adult HSP associated with malignancy in the literature.

Metastatic basal cell carcinoma exhibits reduced actin expression.

Basal cell carcinoma is the most common malignancy in Caucasian individuals. Metastatic basal cell carcinoma is extremely rare (with a rate estimated as 0.03%). Actin has been detected in aggressive forms of basal cell carcinoma, but their expression in metastatic lesions is not known. We compared the expression of actin and actin-related cytoskeletal proteins in relatively less aggressive basal cell carcinoma (nodular), aggressive basal cell carcinoma (infiltrative/morpheaform), and metastatic basal cell carcinoma. We studied 12 cases of nodular basal cell carcinoma, 10 cases of infiltrative basal cell carcinoma, and 10 cases of metastatic basal cell carcinoma with immunohistochemistry for alpha-smooth muscle actin, calponin, myosin, and E-cadherin. Expression was interpreted as positive when at least 5% of the tumor exhibited at least weak expression. Five of the ten patients with metastatic basal cell carcinoma had an antecedent history of radiotherapy. Actin was present in 3 of 12 (25%) of the nodular, all 10 of the infiltrative, and 3 of 10 of the metastatic basal cell carcinomas (P<0.05 for metastatic vs infiltrative and nodular vs infiltrative). Calponin was present in 50% of the nodular, 60% of the infiltrative, and 30% of the metastatic basal cell carcinomas (not statistically significant). Myosin expression was not detected in any of the cases. E-cadherin was present in 75% of the nodular, 70% of the infiltrative, and all of the metastatic basal cell carcinomas (P<0.05 for metastatic vs nodular). Our results suggest that increased actin may contribute to local invasiveness, but it is lost in the metastatic phenotype. History of previous radiotherapy may contribute to development of the metastatic phenotype.

The solitary lymphomatous papule, nodule, or tumor.

BACKGROUND: Lymphoma and reactive lymphoid infiltrates presenting as solitary lesion pose a diagnostic and prognostic dilemma for the clinician. OBJECTIVE: We sought to review prognosis and treatment of suggestive solitary lymphoma lesions. METHODS: A retrospective chart review was conducted in 27 patients who presented with a single solitary lesion suggestive of lymphoma at a cancer center. RESULTS: Eighteen of 27 patients' (66.7%) lesions were diagnosed as lymphoma by histology and the remainder was classified as reactive lymphoid infiltrates. Only one patient's lymphoma was systemic at presentation and one progressed later. In all, 23 patients (85.2%) subsequently experienced prolonged, complete remissions. The treatments used varied from none or conservative to chemotherapy, with the more aggressive treatments directed especially against lymphomas or recurrent diseases. LIMITATIONS: This study is limited by the number of patients and follow-up duration (average 36.8 months, range 3-133 months). CONCLUSION: Patients presenting with a solitary lesion suggestive of lymphoma and negative staging work-up results generally have a good prognosis. Excellent prognosis is usually expected for benign lesions.

Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study.

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.

Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin.

p63, a recently identified homologue of the p53 gene, is mainly expressed by basal and myoepithelial cells in skin. Others and we have shown the value of p63 in distinguishing primary adnexal tumors from visceral adenocarcinomas metastatic to skin. We now investigate the pattern of p63 expression in metastases from skin adnexal carcinomas and their cognate primaries and evaluate p63 expression in a larger case series of malignant cutaneous adnexal neoplasms. Immunohistochemical analysis for p63 was performed on 13 metastases of adnexal carcinomas and their corresponding primary tumors. Twenty visceral metastatic adenocarcinomas to the skin and 7 primary mucinous carcinomas with cutaneous or visceral origin were compared. The majority (90.9%) of primary adnexal tumors strongly expressed p63 and their metastases labeled similar to their cognate primary tumors. With one exception, primary or metastatic mucinous carcinomas did not express p63. Metastases from two apocrine carcinomas lacked p63 expression. All other cutaneous metastases from internal adenocarcinomas were negative for p63. Analysis of p63 expression may assist in the differential diagnosis of primary adnexal carcinomas versus metastatic visceral adenocarcinomas to the skin. Metastases from adnexal carcinomas generally retain p63 expression similar to their associated primary tumors.

Criteria for the diagnosis of antiphospholipid syndrome in patients presenting with dermatologic symptoms.

The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the occurrence of arterial and/or venous thromboembolic events and obstetric complications in the setting of circulating antiphospholipid antibodies. Dermatologic manifestations are commonly seen in APS with almost half of the patients exhibiting varied conditions such as ulceration, splinter hemorrhages, and livedo reticularis. In this paper, we report the case of a 12-year-old boy who was diagnosed with APS after presenting with livedo reticularis and positive antiphospholipid antibodies. We discuss the difficulty of diagnosing APS in patients presenting solely with dermatologic complaints, as these skin manifestations are not specific enough for APS to be included in the Sapporo diagnostic criteria. Proposed revisions to the Sapporo criteria to increase its specificity and sensitivity are also addressed.

Double immunohistochemical staining with MUC4/p53 is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray-based study.

CONTEXT: Immunohistochemical stains have been used for the distinction of pancreatic adenocarcinoma from chronic pancreatitis. OBJECTIVE: To determine if a double stain for MUC/p53 improved specificity and sensitivity for distinction of pancreatic adenocarcinoma from chronic pancreatitis by comparing maspin, mucin 4 (MUC4), p53, Smad4, and the double stain MUC4/p53. DESIGN: Seventy-four pancreatic adenocarcinomas and 19 chronic pancreatitis cases were retrieved from archival files. Tissue cores were arrayed to create a tissue microarray of 2-mm cores. Sections were stained with antibodies against maspin, MUC4, p53, and Smad4. Additionally, a 2-color, double stain for MUC4 and p53 was developed and evaluated. Five percent or greater staining in either of the cores was considered positive. Intensity (0, 1, 2) and extent (%) of tumor cells staining was also determined. RESULTS: The sensitivity for distinction of pancreatic adenocarcinoma from chronic pancreatitis with maspin, MUC4, p53, and Smad4 was 90%, 77%, 60%, and 63%, respectively; the specificity was 67%, 78%, 88%, and 88%, respectively. When MUC4 and p53 were combined in a double stain, and positive staining for either considered a positive result, the sensitivity increased to 96% but specificity was 73%. When immunoreactivity for both antibodies was necessary for a positive result, sensitivity fell to 39% but specificity was 100%. No correlation was found between intensity or extent of staining with any of the individual stains and tumor differentiation. CONCLUSION: The double immunohistochemical stain for MUC4/p53 can be a useful diagnostic tool in conjunction with the hematoxylin-eosin-stained section for pancreatic adenocarcinoma, particularly when limited tumor is available for multiple stains.

Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification by fluorescence in situ hybridization: potential treatment implications.

A 44-year-old man was referred for a right chest nodule of 3 months duration. A 'benign' nodule had been excised from this location 8 years prior. On examination, palpable nodes were noted in the right axilla. Radiographic studies were significant only for right axillary lymphadenopathy. Histologically, a nodular dermal proliferation composed of poorly differentiated epithelioid cells in nests and focally forming ducts with pseudopapillary architecture comprised the primary tumor. Features of a clear cell hidradenoma were noted focally. Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5 and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER), MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and axillary node dissection was performed. Metastatic tumor involved nine of 28 nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated chromosomal amplification of the Her-2/neu locus within the tumor and a nodal metastasis. The patient has completed adjuvant and radiotherapy, including trastuzumab, and is asymptomatic. We believe this to be the first demonstration of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to breast carcinoma, these findings suggest the applicability of trastuzumab for patients with metastatic adnexal carcinomas demonstrating Her-2/neu amplification.

Primary cutaneous CD30+ large cell B-cell lymphoma: a series of 10 cases.

BACKGROUND: White CD30 expression is described in extracutaneous diffuse large B-cell lymphomas, a primary cutaneous B-cell lymphoma (PCBCL) equivalent is not well defined. METHODS: Between June 1999 and July 2002 the authors encountered 10 patients with CD30+ PCBCLs of the large cell type. RESULTS: The patients comprised seven women and three men; five patients were over 80 years of age, all except one presenting with solitary plaques. With the exception of one death from myocardial infarction and one recurrence, all patients are well at a mean follow-up of 23.4 months. Skin biopsies showed a background of T-cell-rich reactive lymphoid hyperplasia in 7 of 10 patients, with variable granulomatous inflammation in 5 cases. The neoplastic large cells were immunoblastic in appearance. In four patients the infiltrate was dominated by large cells. In the remaining patients the reactive infiltrate defined the dominant cell population. The neoplastic cells expressed CD20, CD30, CD43, and BCL-2. In two cases associated with methotrexate therapy, Epstein-Barr virus expression was observed amid the neoplastic cell populace. CONCLUSIONS: CD30+ PCBCL is a distinctive form of B-cell lymphoma presenting in elderly patients and can be associated with a very good prognosis. In some patients the intensity of reactive inflammation obscures the diagnosis. In the authors' experience almost a third of the cases were associated with Epstein-Barr virus infection and methotrexate therapy, suggesting a distinctive association.

The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumors in the liver.

CONTEXT: The distinction of metastatic breast adenocarcinoma (MBA) to the liver from hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and metastatic adenocarcinoma from other sites may require the use of immunohistochemistry. The use of antibodies directed against estrogen receptor (ER) and progesterone receptor (PR) has been suggested to help make this distinction. OBJECTIVE: To examine the utility of ER and PR immunohistochemistry in the distinction of MBA from HCC, CC, and other metastatic adenocarcinomas in the liver. METHODS: Ninety-two previously characterized hepatic neoplasms were identified, including HCC (n = 14), CC (n = 16), and metastatic tumors from breast (n = 17), colorectal (n = 14), pancreatic (n = 15), and esophageal/gastric (n = 16) origins. For all cases of metastatic tumor, the primary tumor was reviewed to verify the diagnosis. All tumors were graded as well, moderately, or poorly differentiated. Estrogen receptor and PR immunohistochemical staining was performed on all cases and evaluated by 2 pathologists. RESULTS: Immunoreactivity for ER was identified only in MBA, with 6 (35%) of 17 cases positive. Positive immunoreactivity for PR was not restricted to MBA, but was seen in HCC, CC, esophageal/gastric, and pancreatic metastases. Positive immunostaining with PR was nearly as frequent in poorly differentiated carcinomas of nonbreast origin (3/16 cases, 19%) as in poorly differentiated breast carcinomas (2/8 cases, 25%). CONCLUSION: Progesterone receptor exhibited poor specificity and sensitivity for the distinction of MBA from HCC, CC, and other metastatic adenocarcinomas. Estrogen receptor exhibited poor sensitivity for MBA, although the specificity was good. The finding that PR positivity was present with a similar frequency in poorly differentiated tumors of breast and nonbreast origin limits the usefulness of this marker. Therefore, ER and PR staining have limited utility in the distinction of MBA from HCC, CC, and other metastatic adenocarcinomas in the liver.

The histopathologic spectrum of cryofibrinogenemia in four anatomic sites. Skin, lung, muscle, and kidney.

Although the histologic characteristics of cryofibrinogenemia have been described in skin lesions, the literature is largely devoid of descriptions of this disorder in other organs. This series is the first to document the histopathologic manifestations of intrapulmonary, intramuscular, and renal cryofibrinogenemia. We describe the histopathologic manifestations of cryofibrinogenemia in 10 cases with manifestations in 4 organ systems: skin in 7 cases, skeletal muscle in 2, lung in 2, and kidney in 1. Irrespective of anatomic site, all lesions showed an occlusive thrombotic diathesis comprising eosinophilic refractile deposits within vessel lumina with extension into the intima, with or without an accompanying characteristic granulomatous vasculitic component. Ultrastructural examination of the renal deposits showed fibrillary material within glomerular capillary lumina with unique morphologic features not previously described. Analysis of plasma from several cases revealed a cold-precipitable protein, which in most cases included a monoclonal paraprotein. The laboratory and histologic distinctions between cryofibrinogenemia and cryoglobulinemia are addressed. We provide guidelines for the proper handling of patient specimens in the workup of cryofibrinogenemia.

To step or not to step: an approach to clinically diagnosed polyps with no initial pathologic finding.

We determined whether there were additional diagnostic findings in additional level sections performed on polyps with no pathologic diagnosis (NPD) or those in which only lymphoid aggregates (LAs) were seen initially and determined the level at which findings were identified. All colorectal biopsy specimens submitted with a clinical diagnosis of polyp during a 6-month period were included (N = 733). Initially, 3 level sections were cut for each polyp, and if a cause for the polyp was found, no additional levels were evaluated. If LAs or no cause for the polyp was found, 5 additional levels through each block were examined. Any diagnostic findings and the level at which they were identified were recorded. A discrete cause for the polyp was identified in routine levels in 574 cases (78.3%). Deeper levels were performed in 159: 23 for clarification of a suspected diagnosis, 38 for LAs, and 98 for NPD. Findings were identified in 31 (22.8%) of 136 stepped for LA or NPD with neoplastic findings in 13 (9.6%). Most diagnoses were identified in levels 4 or 5, but tubular adenomas were found in levels 7 and 8. These results support level sectioning specimens submitted as polyps with NPD or LAs on initial sections.