Microphthalmia transcription factor and melanoma cell adhesion molecule expression distinguish desmoplastic/spindle cell melanoma from morphologic mimics.

Desmoplastic/spindle cell melanoma is a rare variant of melanoma. A number of factors complicate the diagnosis of desmoplastic/spindle cell melanoma, including the variable absence of a lentiginous component, its spindle cell morphology, and its many morphologic mimics, including scars, malignant peripheral nerve sheath tumor, neurofibroma, atypical fibroxanthoma, and spindled carcinoma. The immunohistochemical confirmation of desmoplastic/spindle cell melanoma may also be difficult, because the majority of tumors are negative for specific melanocytic markers such as HMB-45 and Melan-A, despite their usual expression of S-100 protein. Two new and potentially promising melanocytic markers, microphthalmia transcription factor (MiTF) and melanoma cell adhesion molecule (Mel-CAM), have been shown to be sensitive markers of epithelioid melanoma, but have not been tested in desmoplastic/spindle cell melanoma or in other rare melanocytic neuroectodermal tumors such as clear cell sarcoma. We immunostained 79 tumors (20 desmoplastic/spindle cell melanomas, 10 scars, 10 neurofibromas, 12 malignant peripheral nerve sheath tumors, 10 atypical fibroxanthomas, 10 clear cell sarcomas, 3 melanotic schwannomas, and 4 cellular blue nevi) for MiTF and Mel-CAM. MiTF expression was seen in 11 of 20 desmoplastic/spindle cell melanomas, 0 of 10 scars, 2 of 10 neurofibromas, 0 of 12 malignant peripheral nerve sheath tumors, 1 of 10 atypical fibroxanthomas, 7 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 3 of 4 cellular blue nevi. Mel-CAM expression was present in 14 of 17 desmoplastic/spindle cell melanomas, 0 of 10 scars, 4 of 10 neurofibromas, 3 of 11 malignant peripheral nerve sheath tumors, 0 of 10 atypical fibroxanthomas, 9 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 0 of 4 cellular blue nevi. MiTF and Mel-CAM were coexpressed in 6 of 17 desmoplastic/spindle cell melanomas and in no other tumor. Regarding desmoplastic/spindle cell melanoma, scar, neurofibroma, malignant peripheral nerve sheath tumor, and atypical fibroxanthoma, the sensitivity and specificity of MiTF for desmoplastic/spindle cell melanoma were 55% and 91%, respectively. For this same group of tumors, Mel-CAM had a sensitivity of 82% and a specificity of 83%. We conclude that the sensitivity and specificity of MiTF for desmoplastic melanoma equals or exceeds that of such markers as HMB-45 or Melan-A, and that MiTF should be part of the initial immunohistochemical panel for the work-up of such cases. Mel-CAM, while very sensitive, is relatively nonspecific, because it is also expressed in a variety of mesenchymal tumors and carcinomas. Mel-CAM is best reserved for cases morphologically suspected to be desmoplastic/ spindle cell melanoma, in which S-100 is positive and MiTF and other melanocytic markers are negative. These markers may also be helpful in certain other differential diagnoses, such as distinguishing clear cell sarcomas from epithelioid malignant peripheral nerve sheath tumors.

Pancreatic polypeptide: a marker for lean non-insulin-dependent diabetes mellitus?

Both basal and postprandial pancreatic polypeptide (PP) concentrations were exaggerated twofold in lean NIDDM patients, whereas they were normal in lean IDDM and obese NIDDM patients who were hyperglycemic as a result of partial insulin withdrawal. Insulin infusion from an artificial endocrine pancreas, which resulted in fasting euglycemia and near-normoglycemia postprandially, had no effect on PP responses in any of the diabetic patients. No postprandial PP responses were observed in totally pancreatectomized (TPX) patients. Excessive basal and postprandial concentrations of PP in diabetes appear to be related to both leanness and residual beta cell function and, therefore, potential markers for lean NIDDM.

Can plasma human pancreatic polypeptide be used to detect diseases of the exocrine pancreas?

Plasma concentrations of human pancreatic polypeptide (HPP) parallel exocrine pancreatic secretion in response to stimulation with cholecystokinin. We determined prospectively the relationships among fasting HPP level, integrated HPP response to infusion of cholecystokinin, and output of trypsin and also the sensitivity, specificity, and predictive values of the fasting HPP level in the diagnosis of exocrine pancreatic disease. Our study group consisted of 19 patients with acute pancreatitis, 17 with chronic pancreatitis, and 25 with ductal adenocarcinoma of the pancreas and 27 control subjects. In the control patients and those with chronic pancreatitis, significant correlations were detected between HPP level and output of trypsin (P less than 0.001) in response to infusion of cholecystokinin and between fasting HPP and integrated HPP levels (P less than 0.004); no correlation was detected between HPP level and steatorrhea. The sensitivity, specificity, and negative and positive predictive values of the fasting HPP level for detection of either chronic pancreatitis or pancreatic cancer were similar and approximated 0.88, 0.67, 0.88, and 0.66, respectively. The HPP concentration had no value in detecting acute pancreatitis. Because the fasting HPP level has a high degree of negative predictability and is simpler to measure than the integrated HPP level or the output of trypsin, it may be a useful test in patients suspected of having either chronic pancreatitis or pancreatic cancer. A fasting HPP level of 125 pg/ml or greater could be used to exclude chronic pancreatitis or pancreatic cancer, but the finding of a value of less than 125 pg/ml necessitates use of other diagnostic tests for reliable determination of the presence of these diseases.