Jed Goldstein

Diagnostic potential of Fourier-transform infrared microspectroscopy and advanced computational methods in colon cancer patients

Colon cancer is the third leading class of cancer causing increased mortality in developed countries. A polyp is one type of lesion observed in a majority of colon cancer patients. Here, we report a microscopic Fourier transform infrared (FTIR) study of normal, adenomatous polyp and malignant cells from biopsies of 24 patients. The goal of our study was to differentiate an adenomatous polyp from a malignant cell using FTIR microspectroscopy and artificial neural network (ANN) analysis. FTIR spectra and biological markers such as phosphate, RNA/DNA derived from spectra, were useful in identifying normal cells from abnormal ones that consisted of adenomatous polyp and malignant cells. However, the biological markers failed to differentiate between adenomatous polyp and malignant cases. By employing a combination of wavelet features and an ANN based classifier, we were able to classify the different cells as normal, adenomatous polyp and cancerous in a given tissue sample. The percentage of success of classification was 89%, 81%, and 83% for normal, adenomatous polyp, and malignant cells, respectively. A comparison of the method proposed with the pathological method is also discussed.

Distinction of cervical cancer biopsies by use of infrared microspectroscopy and probabilistic neural networks

Fourier-transform infrared spectroscopy has shown alterations of spectral characteristics of cells and tissues as a result of carcinogenesis. The research reported here focuses on the diagnosis of cancer in formalin-fixed biopsied tissue for which immunochemistry is not possible and when PAP-smear results are to be confirmed. The data from two groups of patients (a control group and a group of patients diagnosed with cervical cancer) were analyzed. It was found that the glucose/phosphate ratio decreases (by 23-49%) and the RNA/DNA ratio increases (by 38-150%) in carcinogenic compared with normal tissue. Fourier-transform microspectroscopy was used to examine these tissues. This type of study in larger populations may help to set standards or classes with which to use treated biopsied tissue to predict the possibility of cancer. Probabilistic neural networks and statistical tests as parts of these biopsies predict the possibility of cancer with a high degree of accuracy (> 95%).

Abnormal uterine bleeding as a presenting sign of metastases to the uterine corpus, cervix and vagina in a breast cancer patient on tamoxifen therapy.

Metastases to the female genital tract from extragenital cancers are uncommon. The ovaries are most often affected with the breast and gastrointestinal tract being the most common sites of the primary malignancy. Metastases to the uterus from extragenital cancers are significantly rarer than metastases to the ovaries and in the majority of cases the ovaries are also involved. A case of metastases restricted to the uterine corpus, cervix and vagina from breast carcinoma, without involvement of the ovaries, is described. The patient who had been on tamoxifen therapy presented with postmenopausal bleeding. The diagnosis of uterine metastases was established during endometrial ablation and confirmed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. This case illustrates that abnormal uterine bleeding in a breast cancer patient, regardless of whether she is receiving or not receiving tamoxifen, should always alert the physician to consider the possibility of uterine metastases from breast carcinoma.

Fourier transform infrared microspectroscopy as a quantitative diagnostic tool for assignment of premalignancy grading in cervical neoplasia

The early diagnosis and proper identification of cervical squamous intraepithelial lesions plays an important role in a good prognosis for the patient. However, the present practice of screening based on PAP (Papanicolaou) smear and histopathology makes it tedious and prone to human errors. We assess the validity of FTIR microspectroscopy (FTIR-MSP) of biopsies as a method to properly assign the correct stage of premalignancy in patients with symptoms of cervical intraepithelial neoplasia. For the first time we evaluate the biopsies based on the FTIR spectra for different grades of neoplasia in tandem with probabilistic neural networks (PNNs) and histopathology. The results show that the grading of neoplasia based on FTIR-MSP and a PNN differentiates the normal from premalignant with a high level of accuracy. The false positive identification of the normal as cervical intraepithelial neoplasia 1 (CIN1), CIN2, and CIN3 patients is 9.04, 0.01, and 0.01%, respectively. The false negative identification of CIN2 patients as normal and CIN1 patients is 0.01 and 4.4%, respectively. Similarly, the false negative identification of CIN3 patients as normal, CIN1, and CIN2 is 0.14, 6.99, and 9.61%, respectively. The small errors encountered in the grading are comparable to current methods, encouraging advanced studies for the development of mechanized equipment for the diagnosis and grading of premalignant cervical neoplasia.

FTIR Microscopic Studies on Normal, Polyp, and Malignant Human Colonic Tissues

Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach tooptical diagnosis of tissue pathology based on the characteristic molecularvibrational spectra of the tissue. The biomolecular changes in the cellularand sub-cellular levels developing in abnormal tissue, including a majorityof cancer forms, manifest themselves in different optical signatures, whichcan be detected in infrared microspectroscopy. This report has two parts. Inthe first part, we report studies on normal, premalignant (polyp) andmalignant human colonic tissues from three patients with different stages ofmalignancy. Our method is based on microscopic infrared study (FTIR-microscopy)of thin tissue specimens and a direct comparison with traditional histopathologicalanalysis, which serves as a “gold” reference. The limited dataavailable showed normal colonic tissue has a stronger absorption thanpolypoid tumor and cancerous types over a wide region in a total of 100measurements. Detailed analysis showed that there is a significant decreasein total carbohydrate, phosphate and possibly creatine contents for polyp andcancerous tissue types in comparison to the controls. The same trend is maintainedin seven other patients studied. The second part consists of an analysis showingthe influence of various independent factors such as age, sex and grade of malignancy. Ourpreliminary results suggest that among the above three factors, age and gradeof malignancy have significant effect on the metabolites level, but sex has onlyminor effect on the measured spectra. Initial results on Linear DiscriminantAnalysis (LDA) showed good classification between normal and malignant cellsof human colonic tissues.

Painful ophthalmoplegia associated with lymphoid hyperplasia of the nasopharynx

In the last ten years three patients presented with a subacute syndrome characterized by unilateral frontal headache, ipsilateral external ophthalmoplegia, Va or Vb hypoesthesia and peripheral facial palsy. In all of them, plain X-ray and/or CT revealed a nasopharyngeal mass. Orbital venography failed to fill the superior orbital vein ipsilateral to the ophthalmoplegia, suggesting a unilateral cavernous sinus pathology. Biopsy demonstrated lymphoid hyperplasia. Two patients recovered spontaneously, and in one, steroid treatment resulted in fast pain relief and progressing complete disappearance of the mass. In one patient a high titer of Epstein-Barr viral antibodies was detected.

Myxoma of the nerve sheath. Report of three cases, observations by light and electron microscopy and histochemical analysis

Findings by light and electron microscopy and histochemistry in three cases of myxoma of a nerve sheath are presented. The histochemical findings are compared with those obtained in identical studies done on two benign schwannomas, two neurofibromas, and a soft tissue myxoma. In addition, myxomatous changes in a peripheral nerve obtained at vagotomy were similarly studied.Morphologically, myxoma of the nerve sheath is a distinct neoplastic entity showing moderate cellular aty-pia and a characteristic tissue distribution. Histochemi-cally, the neoplasm shows a mucopolysaccharide profile that categorizes it as a neoplasm of mesenchymal origin rich in highly sulfated acid mucins. Of particular note is its close histochemical similarity to a neurofibroma.

Primary small noncleaved cell lymphoma of the liver : report of an adult case in complete remission after treatment with combination chemotherapy

Open liver biopsy in a 34-year-old woman with hepatosplenomegaly showed small noncleaved cell lymphoma. Except for an enlarged spleen, there was no evidence of other sites of involvement. She was treated with combination chemotherapy and is alive and free of disease > 5 years after diagnosis. We believe this to be the first reported case in an adult of primary hepatic or hepatosplenic lymphoma of the small cleaved cell type with long-term disease-free survival.

Adenocarcinoma of rete testis

Abstract A tumor of the right scrotal content was excised and determined to be an adenocarcinoma of the rete testis. This represents the sixteenth documented case of this most unusual tumor.

A cancer-prone kindred with four siblings afflicted by aggressive poorly differentiated bronchogenic carcinoma

Abstract The A. kindred enumerated ten siblings: 2 females and 8 males. During the years 1982–1988 four brothers, all smokers, at their fifth or early sixth decade, presented with carcinoma of the lung. All patients had their primary lesion located in the right hemithorax, with predominance of the upper lobe ( 3 4 ). The clinical course was relentless with survival ranging 3–14 and 2–11 months from diagnosis and from initiation of treatment, respectively. Symptomatic mediastinal, particularly pericardial disease was common: significant pericardial effusion occurred twice, accompanied by atrial fibrillation in one case. Epicardial deposits occurred in another case. Response to cisplatin-based chemotherapy was minimal. Poorly differentiated carcinoma was the common histologic denominator with apparent presentation of subtypes (squamous-, adeno- and large cell) by haematoxylin and eosin staining. One case had, questionably, small cell carcinoma. Immunoperoxidase staining, however, for neuron-specific enolase was uniformly (3 cases examined) negative. In contrast, tumor tissue ( 3 3 ) stained positively by cytokeratin and epithelial membrane antigens, supporting the diagnosis of non-small cell bronchogenic carcinoma. In addition to the aforementioned brothers afflicted with lung cancer, a female sibling succumbed to a primary brain tumor. Two probands had chronic obstructive pulmonary disease (COPD), which was the cause of death of another brother. Present knowledge lends support to the presumption that the A. kindred was genetically predisposed to bronchogenic cancer either by exogenous carcinogens or due to another hereditary trait. Definite studies are required in order to test this hypothesis.