Desmoplastic Component Research Articles

Desmoplasia in non-small cell lung carcinomas is associated with low programmed death-ligand 1 expression and the absence of tumor-infiltrating lymphocytes.

Programmed death-ligand 1 (PD-L1) is the most widely utilized predictive marker used to identify non-small cell lung carcinoma (NSCLC) patients most suitable for immunotherapy approaches. The relationship between PD-L1 expression, the presence of CD8+ T cells, and other clinicopathological characteristics of NSCLC patients has not been elucidated yet. In this retrospective study, we immunohistochemically determined PD-L1 expression (using clone 22C3) and CD8+ T cell count (using clone c8/144B) in surgical resection specimens from 698 advanced NSCLC patients. Results of PD-L1 expression and CD8+ T cell count were correlated to various clinicopathological characteristics, including the presence of desmoplasia in NSCLC. Regarding the immunological attributes of the tumor microenvironment, we identified major differences between desmoplastic and non-desmoplastic areas in NSCLC. Tumor areas without desmoplasia were significantly more often PD-L1 positive than tumor cell clusters encased in a dense collagenous stroma (p=0.004). Furthermore, the desmoplastic stroma contained significantly less often an immune cell infiltrate rich in CD8+ T cells (p<0.001). Also, the positivity of PD-L1 significantly correlated with advanced N-stage (p<0.001) and poor differentiation in adenocarcinomas (p=0.032) but not with other clinicopathological characteristics. In conclusion, to our knowledge, this is the first study that points to major differences in terms of immunological attributes between desmoplastic and non-desmoplastic areas in NSCLC. The desmoplastic component, therefore, may represent an immunologically distinct tumor area in which PD-L1 immunohistochemistry and CD8+ T cell count should be evaluated separately.

SOX-10 staining in dermal scars.

Positive staining for SOX10 and the S100 protein are often used in the evaluation of challenging melanocytic neoplasms including melanoma in patient samples. SOX-10 positivity of non-melanocytes in re-excision specimen could complicate the evaluation of invasive melanoma with an invasive desmoplastic component. Therefore, quantifiable data regarding the positivity of SOX-10 in scars will help dermatopathologists to better identify false positive staining. A retrospective analysis was performed on 50 re-excision specimens from 2013 to 2017, with a diagnosis of squamous cell carcinoma (SCC) or squamous cell carcinoma in situ (SCCIS). Blocks of re-excision specimens containing scars were stained for SOX-10; results were evaluated by a board-certified dermatopathologist. The sum of the five highest numbers of high-power field (HPF) counts as a proxy for "SOX-10 stain factor," and cell morphological features were analyzed. MART-1 and CD68 immunohistochemical staining was performed to study possible lineage of these SOX-10 positive cells. All 50 specimens showed varying degrees of SOX-10 positivity for histiocytes. SOX-10 positive histiocytes were present in 86% of re-excision scar tissues, of which 71.3% had spindle-shaped or angulated nuclei, and 61.8% had nuclear sizes larger than typical lymphocytes (7 μm). Within the same area of scars, CD68 staining was floridly positive, where as MART-1 staining was overwhelmingly negative. This study illustrates a potential diagnostic pitfall of using SOX-10 to evaluate re-excision specimens of melanocytic neoplasms and also suggests a previously undescribed staining pattern in scars of SOX-10 positive cells that are not melanocytes. We postulate that such SOX-10 positive cells may represent a small fraction of histiocytes routinely found in scar tissue.

Expression of TLE1 in Malignant Melanoma With Spindle Cell Morphology: A Potential Diagnostic Pitfall

Transducer-like enhancer of split 1 (TLE1) immunohistochemistry is widely used as a biomarker of synovial sarcoma. Spindle cell or desmoplastic melanoma can morphologically mimic synovial sarcoma. The aim of this study was to investigate the expression of TLE1 in melanomas with a spindle cell morphology. A search of the surgical pathology files resulted in 57 cases of melanomas diagnosed with a spindle cell or desmoplastic component. After review, 8 cases had no definitive dermal spindle cell component and 7 cases had insufficient tissue remaining and were excluded from the study. A total of 42 melanomas were examined for TLE1 immunohistochemistry using a mouse monoclonal antibody (Cell Marque, clone 1F5). Strength and percentage of nuclear TLE1 positivity was graded on a scale from 0 to 3+. Staining for TLE1 was considered positive for 2 to 3+ and negative for 0 to 1+. Nuclear TLE1 expression was identified in 24 (57%) of the 42 melanoma cases with spindle cell morphology (2+, n = 14; 3+, n = 10). TLE1 was considered negative in 18 cases (43%), of which most contained weak staining (1+, n = 14 [33%]) and only a small subset did not show any staining (0, n = 4 [10%]). TLE1 frequently highlights melanomas with spindle cell morphology and is a potential diagnostic pitfall. Therefore, when evaluating spindle cell tumors in which the differential may include both a melanoma and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an immunohistochemical panel.

Desmoplastic infantile ganglioglioma: A case report and review of literature

Background and objective: Desmoplastic infantile gangliogliomas are rare low grade supratentorial masses that are seen in the pediatric age group. Typically, they involve the superficial cerebral cortex and leptomeninges. Despite the large size of these lesions and some worrisome histological and radiological features, prognosis is generally favorable after gross total resection. To our knowledge, out of about one hundred cases reported worldwide, this is the first Desmoplastic infantile ganglioglioma reported in Kurdistan region-Iraq. Case presentation: We report a case of Desmoplastic infantile ganglioglioma in a 2-month-old male infant, Computed tomography and magnetic resonance imaging revealed a supratentorial mixed cystic and solid temporal tumor. Near total surgical removal was done. Histopathology revealed features of desmoplastic infantile ganglioglioma, with marked desmoplastic component, glial and neuronal elements. Immunohistochemistry showed positive staining for glial fibrillary acidic protein with areas of synaptophysin positivity. Conclusion: The diagnosis of Desmoplastic infantile ganglioglioma should be considered in differential diagnosis of tumors with a cystic component and an aggressive appearance.

Thrombospondin-1 is highly expressed in desmoplastic components of invasive ductal carcinoma of the breast and associated with lymph node metastasis

Desmoplastic (scirrhous) invasion and lymph node metastasis are critical for the treatment and prognosis of invasive ductal carcinoma of the breast. Despite being an anti-angiogenic therapeutic candidate, Thrombospondin-1 (TSP-1) promotes invasion and metastasis of some carcinomas. To clarify the effect of TSP-1 on invasion and metastasis, we obtained 101 invasive ductal carcinomas of the breast with axillary lymph node resection. All tumors were histologically divided into two categories, carcinomas with, and those with non- /minimal desmoplastic component. Immunohistochemistry for TSP-1 was performed on all primary tumors and axillary lymph nodes with tumor metastasis. Fifty-four (53.5%) of 101 tumors were recognized as positive for TSP-1 in the cytoplasm of tumor cells. Histological study showed that significantly more cancers with desmoplastic components (46/69, 66.7%) manifested TSP-1 expression than did cancers with no- or minimal (less than 20%) desmoplasia (8/32, 25.0%; p<0.001). Axillary lymph node metastasis was significantly higher in TSP-1-positive- (28/54, 51.9%) than TSP-1-negative cancers (11/47, 23.4%; p<0.005). The present study indicates that tumor cells in the desmoplastic component strongly expressed TSP-1 in invasive ductal carcinoma of the breast and TSP-1 participates in invasion of these tumors. Our findings also suggest that TSP-1 promotes lymph node metastasis and TSP-1 potentially could be a predictive marker for metastasis.

23‐YEAR‐OLD MAN WITH A SUPERFICIAL CORTICAL BRAIN TUMOR

A 23-year-old male presented with a tonic-clonic generalized seizure. Neuroradiological examination revealed a superficial cystic mass with a mural nodule in the right fronto-parietal lobe. Histological and immunohistochemical examination were consistent with a pigmented (melanin producing) desmoplastic ganglioglioma.These tumors have been first described in childhood, one of them displaying melanin deposits. Only twenty cases of non-infantile desmoplastic gangliogliomas have been reported in the literature, none of them pigmented. According to the clinical and histomorphology (including the desmoplastic component) features, the differential diagnosis should include the ganglioglioma, the xanthoastrocytoma pleomorphic (both tumors also with pigmented forms) and the superficial desmoplastic infantile astrocytoma.

An Update on Reporting Histopathologic Prognostic Factors in Melanoma

Accurate diagnosis of melanocytic lesions is essential for the adequate clinical management of patients. Thus, thorough reporting of histopathologic parameters, especially in the initial biopsies, is a critical component of both diagnosis and staging. To review current data on histopathologic prognostic factors for melanoma, with special emphasis on their use and applicability to clinical practice. Special attention is focused on the criteria highlighted by the new 2009 version of The American Joint Committee on Cancer (AJCC) system of melanoma staging and classification. Published peer-reviewed literature and personal experience of the authors. When reporting melanoma, we recommend that a template be provided, including all the histologic parameters that have been proved significant in determining the tumor staging and prognosis of a patient. The template may also include other details that may be helpful in further analysis of potential complete excisional biopsies or metastatic lesions, such as predominant type of tumor cells, presence or absence of desmoplastic component, or associated benign melanocytic lesions. Although there are several drawbacks in reporting some of these histopathologic parameters (interobserver variability, occasional lack of a perfectly reproducible method for quantifying these criteria), we suggest that at least the essential histopathologic parameters highlighted by the newest version of the AJCC system for melanoma staging and classification should be included in the report.

Clinical and pathological features of metastases of primary cutaneous desmoplastic melanoma

Primary cutaneous desmoplastic melanoma (DM) may be entirely desmoplastic ['pure' DM (pDM)] or exhibit a desmoplastic component admixed with a non-desmoplastic component ['combined' DM (cDM)]. Our aim was to describe the histological features of metastases of primary DM and to determine whether they were predictive of outcome. The effect of clinicopathological parameters on overall survival (OS) was analysed, and the correlation between histological features of the primary melanoma and metastases was studied in patients with metastatic DM. Twenty-six patients (18 males; eight females) developed 50 metastases in sentinel nodes (13; 26.0%), regional nodes (10; 20.0%), skin (14; 28.0%), and distant sites (13; 26.0%). The cellular composition of metastases correlated with that of the corresponding primary tumours. Time to development of first non-sentinel lymph node metastasis was shorter in cDM than in pDM (median 11.2 versus 24.9 months, P = 0.075). The only independent predictors of poorer OS were cDM type [hazard ratio 6.17, 95% confidence interval (CI) 1.61-23.81, P = 0.008] and male sex (hazard ratio 5.98, 95% CI 1.34-26.66, P = 0.019). The cellular composition of primary DM correlates with that of metastatic DM and with outcome. It is important to consider the possibility of primary or metastatic DM when examining tumours composed of spindle cells.

27. Pathological features of metastases from primary cutaneous desmoplastic melanoma

Background Desmoplastic melanoma (DM) is characterised by malignant spindle cells associated with prominent fibrocollagenous stroma. Primary melanomas may be entirely desmoplastic (‘pure’ DM, pDM) or exhibit a desmoplastic component admixed with a non-desmoplastic component (‘combined’DM, cDM).Wesoughtto correlate the features of primary DM with those of metastases. Methods The study cohort included patients with metastatic DM, in whom slides from the primary and metastatic tumours were available for review. Correlation between histological features of the primary melanoma and metastases was analysed. The effect of clinico-pathological parameters on overall survival (OS) and SLN positivity was analysed. Results 26 patients (18 males, 8 females) developed 50 metastases. Metastases from primary cDM more commonly (53.2%) involved lymph nodes than those from primary pDM (33.4%; p = 0.03). Primary melanomas composed predominantly of spindle cells were associated with increasing % of spindle cells ( r = 0.40, p = 0.007) and decreasing % of epithelioid cells ( r = –0.41, p = 0.005) in the metastases. Primary pDM was strongly associated with extensive desmoplasia in the MM (r = 0.57, p p =0.08). Independent predictors of poorerOSwere cDM type(hazard ratio6.17,95%CI1.61–23.81) and male sex (hazard ratio 5.98, 95%CI 1.34–26.66). Conclusions The cellular composition of metastases from primary cutaneous DM correlate with the composition of the primary tumours. It is important to consider the possibility of primary or metastatic desmoplastic melanoma when examining tumours composed of spindle cells.

P75 nerve growth factor receptor staining is superior to S100 in identifying spindle cell and desmoplastic melanoma

Spindle cell melanoma (SCM) including desmoplastic melanoma (DM) is a rare variant of malignant melanoma that may present diagnostic difficulties particularly when staining with S100 is negative, weak, focal, or a combination of these. Conventional melanocytic markers in SCM are usually negative. We sought to compare the staining of p75 nerve growth factor receptor (NGF-R) and S100 in SCMs. We evaluated the staining of p75 NGF-R and S100 in 13 cases of SCMs: 3 SCMs without desmoplasia, 5 pure DMs, and 5 combined DMs with a conventional component. Staining with p75 NGF-R was positive in 13 of 13 (100%) cases of SCMs. In 3 cases the intensity of staining and the percentage of cells staining with this marker were greater than those with S100. One case of SCM was negative for S100 but demonstrated strong expression of p75 NGF-R. One case was focally and weakly positive with S100 but expressed strong positive staining with p75 NGF-R. Absence of staining with p75 NGF-R was noted in the conventional round cell component of two of 5 (40%) combined DMs whereas the same areas were strongly positive for human melanoma black (HMB)-45 and Melan-A. In 5 of 5 (100%) cases of combined DMs the desmoplastic component stained positive with p75 NGF-R, demonstrating an inverse relationship with the staining of conventional melanocytic markers. Small study size was a limitation. p75 NGF-R exhibits superior staining characteristics and greater sensitivity in identifying SCM and DMs than S100. P75 NGF-R may be a useful diagnostic and ancillary stain in addition to S100.

Prognostic factors in cutaneous desmoplastic melanoma

Desmoplastic melanoma (DM) is a rare subtype of melanoma that is characterized by malignant spindle cells separated by prominent, fibrocollagenous stroma. Primary melanomas either may be entirely desmoplastic or almost entirely desmoplastic (pure DM [pDM]) or may exhibit a desmoplastic component admixed with a nondesmoplastic component (combined DM [cDM]). Patients who were diagnosed between 1993 and 2007 at a single institution with clinically localized, primary cutaneous melanoma (PCM) that contained a desmoplastic component and who underwent sentinel lymph node (SLN) biopsy were identified. Clinical and pathologic features of the primary tumors were correlated with DM type, SLN status, and patient outcome. Two hundred fifty-two patients (167 men, 85 women) were identified (median age, 61 years). The median tumor thickness was 2.0 mm. One hundred twenty-three patients (48.8%) had pDM, and 129 patients (51.2%) had cDM. Overall, 17 patients (6.7%) had positive SLN status, including 12 patients with cDM and 5 patients with pDM. Because of the low SLN-positive rate, a statistically significant difference in SLN status between patients with cDM (8.5%) and patients with pDM (4.9%; P = .25) could not be demonstrated. Older patient age, being a man, positive SLN status, and increasing tumor thickness were associated significantly with poorer disease-free survival (P < .05), although only the latter 2 variables were independently predictive. In addition, cDM type (P = .017) was associated significantly and independently with a shorter time to recurrence. In this largest study to date of patients with DM who underwent SLN biopsy, the SLN-positive rate in patients with DM was lower than that in patients with conventional melanoma. The results indicated that DM type is associated significantly and independently with the time to recurrence and should be evaluated routinely in all patients with PCM. Cancer 2010. (c) 2010 American Cancer Society.

Cytologic Features of Metastatic and Recurrent Melanoma in Patients with Primary Cutaneous Desmoplastic Melanoma

Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by malignant spindle cells associated with prominent fibrocollagenous stroma. Primary melanomas may be entirely desmoplastic ("pure" DM) or exhibit a desmoplastic component admixed with a nondesmoplastic component ("combined" DM). The cytologic features of only 5 cases of DM have been reported previously. Fine-needle biopsy (FNB) specimens from 20 recurrent or metastatic lesions in patients with cutaneous DM and 20 recurrent or metastatic lesions from patients with primary cutaneous non-DM were examined and compared. FNB specimens of patients with DM were less cellular (P = .009) and less often exhibited intranuclear cytoplasmic invaginations (P = .008) and mitotic figures (P = .006) than specimens from patients with non-DM. "Combined" DMs were more commonly composed of epithelioid cells (P = .017) and less often contained bizarre/giant tumor cells (P = .010) than did "pure" DMs. Recurrent and metastatic DM has a range of cytologic appearances. Awareness of the cytologic features and careful clinicopathologic correlation will assist in accurate FNB diagnosis.

Desmoplastic Malignant Melanoma: A Clinicopathologic Analysis of 113 Cases

Desmoplastic melanoma (DM) is a rare variant of spindle cell melanoma, which usually develops in sun-damaged skin of elderly patients. Often the lesion is nonpigmented and frequently mistaken for a nonmelanocytic proliferation, which delays diagnosis and treatment and therefore worsens the prognosis. The spindle shape of neoplastic melanocytes, the prominent desmoplasia, and the frequent neurotropism of neoplastic melanocytes are its most characteristic histopathological features. We have studied the clinicopathologic features of 113 cases of DM. The mean age of the patients was 71.1 years; 48% of the patients were males and 52% were females. The neoplasm was located on the head in 72% of the cases. Malignant melanoma was the initial clinical diagnosis in only 27% of the cases. Histopathologically, all lesions appeared as poorly demarcated neoplasms that involved the entire dermis and often extended into the subcutaneous tissue. The neoplasms were composed of ill-defined fascicles of spindle cells. Desmoplasia was defined as the presence of spindle cells associated with a fibrotic stroma. Fifty-one cases (45%) were classified as "pure DM" when the lesion was entirely desmoplastic, and 62 cases (55%) were considered as "combined DM" when a recognizable desmoplastic component was seen in an otherwise conventional malignant melanoma. In 81% of the cases, an atypical intraepidermal melanocytic component (in situ malignant melanoma) was identified, whereas in the remaining 19% of the cases the intraepidermal component was lacking. Seventy-one percent of the cases were histologically amelanotic, 23% showed a small amount of pigment, and only 6% were heavily pigmented. Neural involvement was identified in 40/113 cases (35%), predominantly in the thickest tumors. Lymphoid nodules, found in 42/113 cases (37%), were significantly more frequent in pure DM than in combined DM (53% vs 24%). The null hypothesis of homogeneity of the "pure" and "combined" subgroups should be rejected (P < 0.002). Solar elastosis, with variable intensity, was seen in 82% of the cases. Mean Breslow thickness was 4.1 mm (4.6/3.7 mm, in the pure/combined subgroups, respectively), median was 4.0 mm (4.0/3.0 mm); Breslow thickness ranged from 0.3 to 11.0 mm, with half of the cases thicker than 4 mm. Only 4% of the cases showed Clark level below IV. The predominant neoplastic cells consisted of spindle-shaped melanocytes in 85% of the cases, whereas the remaining 15% of the cases demonstrated round neoplastic cells forming the main mass of the neoplasm. The mitotic rate of the neoplastic cells was low in 72% of the cases, 23% had an intermediate mitotic rate, and 5% showed a high mitotic rate. On follow-up, 55/113 patients (49%) (with an average of 55 months) demonstrated persistence of the disease. About 4% had local recurrences, 2% of lymph node invasion, 9% systemic metastases, and 12% died from the disease (2 cases of pure DM and 5 cases of combined DM). Although a better prognosis has been postulated for DM when compared with conventional cutaneous malignant melanomas of the same thickness, in most cases, a DM is diagnosed only in established long-standing and thick melanomas. Therefore, dermatologists and dermatopathologists should be more aware of this clinicopathologic variant of cutaneous malignant melanoma.

Primary cutaneous diffuse leiomyosarcoma with desmoplasia

A 65-year-old man presented with an indurated plaque over his left cheek and left neck. An initial punch biopsy of skin showing increased smooth muscle bundles was consistent with a diagnosis of smooth muscle hamartoma. A second incisional skin biopsy revealed a well-differentiated smooth muscle proliferation invading into the dermis and subcutaneous fat in a diffusely infiltrative pattern and with a desmoplastic component, suggesting a diagnosis of desmoplastic leiomyosarcoma. Resection of the tumour confirmed the presence of a cytologically low grade leiomyosarcoma with an insidious infiltrative growth pattern. This rare pattern of diffuse leiomyosarcoma is important to recognize as the histological features are subtle and may potentially constitute a pitfall in histological diagnosis in a small biopsy specimen. In addition, our case illustrates overlapping morphology between diffuse and desmoplastic types of leiomyosarcoma.

Long-term relapse-free survival with supratentorial primitive neuroectodermal tumor in an adult: a case report

In adults, supratentorial primitive neuroectodermal tumor (sPNET) is a very rare undifferentiated embryoblastic neoplasm. Prognosis is worse in comparison to infratentorial medulloblastoma. Older age appears to be prognostically favorable. At present, 5-year survival rates remain below 50% in all age groups. Survival longer than 15 years in an adult has only been reported once so far. In 1987, a 33-year-old-male patient presented with seizures following a six-month's history of dizziness. CT- and MRI-scans revealed a right occipital tumor with moderate contrast enhancement. The tumor was completely removed. The original histological diagnosis was that of an undifferentiated sarcoma, malignant hemangioendothelioma, grade III. The patient was treated by CyVADIC chemotherapy and conventional radiation therapy (60 Gy). Admission for another reason in 2003 led to a re-evaluation of the original diagnosis. Microscopy revealed a malignant, highly cellular, poorly differentiated tumor with a desmoplastic component. Up to 20% of tumor nuclei were labeled for Ki-67. Almost all cells were stained for neuron specific enolase and NGF-Rp75, with neuronal and glial markers being present to a variable extent. According to these findings, the diagnosis was changed to a sPNET (WHO IVdegrees ). Other tumor entities were excluded by immunohistochemistry. Although the prognosis of sPNET is reported to be poor, a small fraction with a rather benign biological and clinical behavior exists. Parameters determining long-term-survival in sPNET are not yet known. Whenever possible, complete surgical resection should be attempted followed by postoperative radiotherapy. The value of chemotherapy is an issue of continuous investigation.

Desmoplastic melanoma: a diagnostic trap for the unwary

Desmoplastic melanoma (DM) is an uncommon type of spindle cell melanoma in which the malignant cells are separated by collagen fibres or fibrous stroma. DM is prone to misdiagnosis because of unfamiliarity with its often bland appearance and dissimilarity to other conventional types of melanoma. It displays variable cytological atypia, cellularity and stromal fibrosis and more often than not has an accompanying atypical junctional component. Neurotropism is a common associated feature (in at least 30% of cases) and when it occurs such tumours are termed 'desmoplastic neurotropic melanomas' (DNM). The neurotropism may be perineural or intraneural and often extends beyond the desmoplastic component. In addition, some DMs show evidence of neural differentiation ('neural transformation'). DM may also present as a recurrence or occasionally as a metastasis from other types of melanoma. A high index of suspicion and knowledge of its often subtle morphological appearance are necessary to avoid misdiagnosis.

Multidisciplinary management of perihilar bile duct cancer.

Cancers of the extrahepatic biliary system remain a challenge to surgical, medical, and radiation oncologists. Although surgical resection is the only curative option, many patients are incurable at the time of diagnosis and palliative treatment is often undertaken. Understanding the options for surgical resection and the limits of operative intervention is critical in caring for these patients. Cholangiocarcinoma may occur intrahepatically, or extrahepatically in perihilar or distal ductal locations. Perihilar lesions constitute approximately 75% of tumors. Distal bile duct tumors and intrahepatic tumors follow in frequency. This anatomic classification has therapeutic relevance. Intrahepatic tumors are treated with liver resection; distal tumors are managed, as are pancreatic cancers, with pancreaticoduodenectomy. Perihilar cancers require a combination of operative and nonoperative approaches and will be the focus of the current discussion. In the United States strong associations have been made between cholangiocarcinoma and biliary cystic disease, sclerosing cholangitis, and ulcerative colitis. In autopsy series as many as 40% of patients with sclerosing cholangitis have been shown to have cholangiocarcinoma, often undiagnosed in life. Approximately one third of patients undergoing hepatic transplantation for liver failure secondary to sclerosing cholangitis are discovered, on histologic examination of the recipient hepatectomy, to have bile duct cancer. The association of sclerosing cholangitis with ulcerative colitis provides the link of the latter condition with bile duct cancer. In East Asia, liver flukes and hepatolithiasis are both associated with cholangiocarcinoma. The large majority (90%) of bile duct tumors are adenocarcinomas. Most lesions demonstrate a diffuse infiltrative pattern of growth with a strong desmoplastic component, making the pathologic demonstration of malignancy notoriously difficult. Percutaneous fineneedle aspiration biopsy has the highest diagnostic yield, although biopsy is often hampered by the absence of perihilar mass effect. Luminal brush biopsy and cytologic examination of bile are alternatives of lower diagnostic value. The typical patient is between 60 and 65 years of age; men and women are affected with approximately equal frequency. Jaundice will develop in greater than 90% of patients with perihilar cholangiocarcinoma. Serum liver tests demonstrate hyperbilirubinemia and disproportionate elevation in alkaline phosphatase. Most patients will have a serum bilirubin level greater than 10 mg/dL. Bilirubin elevations to this level are unusual for nonmalignant causes of jaundice. Serum levels of carcinoembryonic antigen (CEA), -fetoprotein, and CA 19-9 are usually normal when biliary obstruction is relieved. Cholangitis is not usually a presenting problem in the absence of earlier biliary manipulation. Anorexia, upper abdominal pain, and weight loss are common, but nonspecific, symptoms.

Expression of the neurotrophin receptor p75NTR in medulloblastomas is correlated with distinct histological and clinical features: evidence for a medulloblastoma subtype derived from the external granule cell layer.

Medulloblastomas (MBs) are primitive neuroectodermal tumors (PNET) of the cerebellum. They represent the most frequent malignant pediatric brain tumors, but their origin still remains unresolved and controversial. MB cells correspond to different stages of neural development and differentiation as illustrated by their expression of neuronal and glial markers. In the present study, we examined the expression pattern of the common low-affinity neurotrophin receptor p75NTR in a series of 167 MBs by immunohistochemistry. While p75NTR was present in only 17% of classic MBs (CMB), we found expression of p75NTR in all desmoplastic (nodular) MBs (DMB) examined, and in 71% of those MBs with a significant desmoplastic component. Furthermore, both desmoplastic histology and p75NTR expression were present preferentially in those tumors of adolescents and adults that are frequently located laterally in the cerebellar hemispheres. In DMBs, p75NTR was expressed predominantly in the proliferative, reticulin-rich areas, which may show coexpression of GFAP. In the pale islands of DMB, p75NTR was expressed only weakly or was absent. The expression pattern showed an inverse relation to that of the synaptic vesicle protein synaptophysin that was predominant in p75NTR negative classic MBs. Since the neurotrophin receptor p75NTR is expressed in cells of the external granule cell layer (EGL) of the fetal cerebellum, our findings suggest that progenitor cells of the EGL are the cellular origin of a distinct subset of MB, namely the desmoplastic variant and MBs with a significant desmoplastic component.

Diagnostic value of CD34 immunostaining in desmoplastic trichilemmoma.

Desmoplastic trichilemmoma (DT) is a variant of trichilemmoma, characterized by a central prominent desmoplastic component which may simulate invasive carcinoma. We have studied the morphologic and immunohistochemical features of seven cases of DT. Immunohistochemistry was performed on paraffin sections using monoclonal antibodies to CD34 (QBEND/10), vimentin and GCDFP-15. CD34 was also tested in seven cases of basal cell carcinoma (BCC), three with outer root sheath differentiation and four with morphea-form features, and five squamous cell carcinomas. Histologically, features of conventional trichilemmoma were seen at the periphery of the seven lesions. In contrast, at the center, the epithelial cells tended to cluster in narrow irregular cords and nests entrapped in a dense collagenous stroma. One case of DT coexisted with a BCC. In all cases of DT, epithelial tumor cells showed CD34 immunostaining. All cases of BCC, including the one contiguous to a DT, were CD34 negative. CD34 immunodetection in the epithelial cells of the pseudoinvasive component of DT may be of great value in the differential diagnosis with other desmoplastic tumors of the skin, and particularly with BCC.

Chemotherapy for pancreatic carcinoma

Pancreatic cancer is an aggressive disease and its patients typically have a short survival, usually marked by pain and rapid debilitation. The disease has been considered relatively chemoresistant, although many chemotherapy regimens have been described. Clinical results with chemotherapy, since the first publication of response in 1960, were reviewed for efficacy and toxicity. Emphasis was given to prospective trials with adequate power and clear evaluation criteria and endpoints. Published response rates vary enormously in this disease, with rates in earlier single-institution trials tending to be much higher than those in studies with stringent response criteria, particularly recent cooperative group trials. Using stringent criteria, the upper limit of the objective response rate is approximately 20%. No convincing improvements in median survival can yet be attributed to chemotherapy. Few trials have measured quality of life, but symptomatic palliation rates may exceed objective response rates. Some low-toxicity regimens (such as those based on infusional 5-FU) yield response rates as high as some more toxic combinations. Many early trials significantly overstate the efficacy of chemotherapy for patients with pancreatic cancer, apparently due to flexibility of response criteria. However, useful symptomatic palliation may occur even without an objective partial response. It is possible that slow resolution of the desmoplastic component of these tumors may underestimate tumor killing. Thus, quality of life is an important parallel endpoint (with survival and response) in chemotherapy trials in this disease.