Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.     

Thyroid nodules in Graves disease and the risk of thyroid carcinoma.

BACKGROUND: The risk of thyroid carcinoma in patients with Graves disease has been particularly emphasized when nodules coexist with thyroid hyperplasia; a surgical approach has been suggested. OBJECTIVES: To detect thyroid nodules early in patients with Graves disease and to evaluate the risk of carcinoma. METHODS: The study group included 315 consecutive outpatients with Graves hyperthyroidism not previously treated with surgery or radioiodine therapy. Thyroid ultrasonography was performed at the time of enrollment and repeated annually in all patients; fine-needle aspiration (FNA) was carried out in those patients with nodules and repeated after 2 years or at shorter intervals. RESULTS: One hundred six of 315 patients with Graves disease had thyroid nodules 8 mm in diameter or larger detected by ultrasonography. In 49 patients, nodules were present at the time of the first examination; in 57 patients, nodules developed during follow-up. Fine-needle aspiration cytology results revealed features of carcinoma in only 1 patient; this was confirmed by histologic examination of excised thyroid tissue. The nodules with normal cytologic features at the time of the first examination did not show any clinical and/or cytologic evolution toward malignancy during follow-up. CONCLUSIONS: Ultrasonographic evidence of nodules was frequently found among our patients with Graves disease, but malignant FNA cytologic findings of the examined nodules were rare at the time of diagnosis and throughout the course of the disease. When FNA cytologic evaluation does not indicate malignancy, the presence of thyroid nodules in patients with Graves disease does not indicate an aggressive therapeutic approach.     

Recurrent cavitary nodules secondary to Hodgkin's disease

A patient with nodular sclerosing Hodgkin's disease had at least three episodes of lung involvement consisting of an infiltrate on one occasion and multiple cavitating nodules on the other two. The cytologic and histologic studies of the lung specimens disclosed the presence of Reed-Sternberg cells on each occasion without any evidence for infection. This represents the first time in which recurrent cavitating nodules have been reported with Hodgkin's disease.     

The spectrum of computerized tomography (CT) findings in central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii in immunocompetent children

Cranial CT scans of eleven immunocompetent children with central nervous system (CNS) infection due to Cryptococcus neoformans var. gattii were retrospectively reviewed. These children had an average age of 8.8 years and positive culture for C. n. var. gattii in cerebrospinal fluid. The most common signs and symptoms were headache, fever, nuchal rigidity, nausea and vomiting. No normal cranial CT was detected in any patient. Hypodense nodules were observed in all patients. The remaining scan abnormalities were as follows: nine had diffuse atrophy, six had hydrocephalus, and five had hydrocephalus coexistent with diffuse atrophy.     

Pulmonary hyalinizing granuloma presenting as multiple cavitary calcified nodules.

We describe a patient with PHG who presented with multiple cavitary calcified nodules. Laboratory evaluations revealed that she had serum immune abnormalities, and a histoplasmin skin test yielded positive results. Her Histoplasma infection may have produced a hyperimmune reaction that resulted in PHG and the calcified nodules.     

Palindromic rheumatism with rheumatoid nodules: a case report with ultrastructural studies.

Rheumatoid nodules developed on the finger tips of a patient with palindromic rheumatism. The patient had no bone cysts or erosions and had no rheumatoid factor. A light microscopic and ultrastructural study of a nodule showed a necrotic centre with fibrin, collagen, and granular material surrounded by large histiocytes, fibrocytes, lymphocytes, and vessels with adjacent mast cells as has been seen with nodules in classical rheumatoid arthritis (RA). We describe the first immunoperoxidase studies on a rheumatoid nodule and have identified reaction products for immunoglobulins and C3 in perivascular and endothelial cell vacuoles and in the necrotic centre.     

Sarcoidosis following adjuvant high-dose methotrexate therapy for osteosarcoma.

A patient who had undergone amputation and adjuvant chemotherapy with methotrexate doxorubicin hydrochloride for osteosarcoma of the femur later developed granulomatous hilar and paratracheal lymphadenopathy and multiple pulmonary nodules. Biopsy of the nodules showed noncaseating granulomas typical of sarcoidosis. Hilar adenopathy and granulomatous pneumonitis have been reported following methotrexate therapy, but a roentgenographic pattern of isolated, discrete pulmonary nodules has not been described. Treatment with immunosuppressive chemotherapy may have inhibited the development of sarcoidosis, which became manifest only after cessation of the chemotherapy.     

Benign Rheumatoid Nodules

Summary: Nine cases in which subcutaneous rheumatoid nodules were observed in the absence of any evidence of rheumatoid arthritis are recorded. In four of these cases, the nodules appeared during adolescence or adult life, a very rare phenomenon. Synovitis occurred in only one patient, after an interval of 15 years, but it did not persist and other features of rheumatoid arthritis were not present. The siting of the nodules in the sub-cutaneous tissue, the absence of features suggestive of rheumatic fever, necrobiosis lipiodica or fungal infection, and lack of any history of trauma, together with the histological appearance, supported a diagnosis of rheumatoid nodules. In all cases, serological tests for rheumatoid factor were negative but in the only case investigated with immunofluorescent staining, IgG and IgM were demonstrated in the biopsy material.
It is important to recognise the fact that these benign nodules do not necessarily indicate that the patient has rheumatoid arthritis, or will develop rheumatoid arthritis in the future. The possible relationship of such nodules to granuloma annulare is discussed.     

Lack of association between thyroid and adrenal nodules: a histological study.

The prevalence of thyroid nodules is increased in patients with Cushing's disease, but the possibility of an association between thyroid and adrenal nodules in other patient groups has not been formally tested. We have evaluated the co-existence of thyroid and adrenal nodules in retrospective and prospective autopsy studies. Retrospective (83 autopsies) and prospective (29 autopsies) blinded studies of thyroid and adrenal gland histopathology were performed by two experienced histopathologists in unselected autopsies. The presence of nodules, defined as areas of tissue having discrete edges within the gland parenchyma seen as a step difference between the cells or architecture adjacent to the nodule, was determined for each gland. No association was found between the presence of adrenal and thyroid nodules in either the retrospective or prospective studies (p>0.2 for both). In the retrospective study, 23% of specimens had thyroid nodules and 28% adrenal nodules. In the prospective study, 24% of specimens had thyroid nodules and 7% adrenal nodules. The proportion of patients with adrenal nodules in the prospective study was significantly less than that in the retrospective study. In conclusion, thyroid and adrenal nodules are frequent autopsy findings in the general population but we have found no evidence of a relationship between the occurrence of nodules in these glands.     

Ultrasound-guided aspiration biopsy of small peripheral pulmonary nodules.

We compared the diagnostic yields of ultrasound-guided aspiration biopsy, sputum cytology, and fiberoptic bronchoscopy with biopsy in 30 patients with peripheral pulmonary nodules smaller than 3.0 cm in diameter. Among them, there were 4 minute nodules with diameter less than 1.0 cm, 12 between 1.1 to 2.0 cm, and 14 between 2.1 to 3.0 cm. The final diagnoses in these 30 patients, as confirmed by histologic findings, microbiology, and clinical follow-up, revealed 24 malignant lesions and 6 benign. All of these 30 nodules received ultrasound-guided transthoracic fine-needle aspiration biopsy, and confirmative diagnoses were obtained in 27 (90 percent). Twenty-two (92 percent) of 24 patients with malignant nodules had positive cytology for malignancy and 5 (83 percent) of 6 patients with benign lesions had diagnosis made by cytologic and microbiologic examinations. One patient developed asymptomatic pneumothorax after needle aspiration. The size of the lesions did not affect the diagnostic yield and complication rate. None of the lesions was diagnosed by sputum cytology (0 of 19; 0 percent). Two patients had diagnoses obtained by fiberoptic bronchoscopy with biopsy (2 of 10; 20 percent). We conclude that ultrasound-guided aspiration biopsy is a useful and safe method for diagnosis of peripheral pulmonary nodules, even when the size of the nodule is less than 3 cm in diameter. The diagnostic yield far exceeds that which can be obtained by sputum cytology and fiberoptic bronchoscopy with biopsy.     

Evaluation and management of solitary and multiple pulmonary nodules.

The evaluation and management of a patient with an SPN is guided by principles that were derived from earlier surgical studies. Stability or no growth for at least 2 years, the presence of calcium in characteristic patterns, and age less than 35 years without any associated risk factors are reliable indicators of a benign process. Fluoroscopy and localized tomography are helpful in evaluation of an SPN. If the nodule is still considered indeterminate, CT scanning, with the use of thin section cuts through the nodule, is now widely employed. If calcium is present in a characteristic pattern, the nodule is considered benign. If the nodule is very dense or more dense than a phantom reference nodule, the nodule has a high likelihood of being benign. Nodules that are less dense than the phantom nodule are indeterminate, and approximately 25% of these nodules will be benign. Computed tomography scan of the chest and upper abdomen is indicated in patients with a previous history of malignancy or when there is a high suspicion that the nodule is malignant. The further evaluation and management of SPNs that are indeterminate after CT examination are controversial. Some recommend tissue biopsy via transbronchoscopic or transthoracic approach, whereas others recommend immediate thoracotomy. Observation is indicated in certain situations when the chance of malignancy is quite low, the patient is not an operable candidate, or when the patient refuses further invasive evaluation. The physician's role in the management of a patient with an SPN is to educate and advise. The physician must be aware of the patient's anxieties, fears, and attitude and provide an opportunity for active participation by the patient in the decision-making process. Multiple pulmonary nodules are most commonly encountered in patients with metastatic disease to the lungs. Other less commonly encountered diseases that present as multiple pulmonary nodules include infections, arteriovenous malformations, Wegener's granulomatosis, and lymphoma. The evaluation and management of the patient with multiple pulmonary nodules are usually guided by the history, physical examination, and laboratory findings.     

A case of pulmonary Langerhans' cell histiocytosis with liver involvement]

We report a case of pulmonary Langerhans' cell histiocytosis with liver involvement in an adult. An asymptomatic 51-year-old man who had, until his referral to our hospital, been a smoker was suspected on examination to have multiple metastases to the lungs and liver. Chest CT showed multiple micronodules, located predominantly in the upper and middle lung fields. Many of these nodules were cavitary. Abdominal US showed multiple, well-defined, round and oval nodules of decreased echogenicity within the liver. Hepatic nodules were enhanced rapidly by contrast-enhanced CT. Comparatively large nodules were demonstrated as well-circumscribed hypoattenuating lesions with ring enhancement. Since further work-up did not demonstrate any evidence of malignancy, open lung biopsy was performed. The results of open lung biopsy were consistent with Langerhans' cell histiocytosis. The infiltrates consisted of variable numbers of Langerhans' cells with folded nuclei and eosinophils. Immunohistochemically, the histiocytes were positive for S-100 protein and CD1a, and negative for CD68. The nodules regressed within 5 months after smoking cessation, and the patient became free of disease 10 months after the initial presentation.     

Incidental adrenal nodules: association with exaggerated 17-hydroxyprogesterone response to adrenocorticotropic hormone.

The etiology of incidentally discovered, nonfunctional adrenal nodules was evaluated by using the 17-hydroxyprogesterone (17-OHP) response to synthetic adrenocorticotrophin (cosyntropin) (ACTH) administration. Patients who were discovered to have adrenal nodules and age-matched volunteers were studied. A total of 12 patients with adrenal nodules and 10 control subjects were studied. None of the patients with adrenal nodules had any evidence of hormonal hypersecretion consistent with pheochromocytoma, Cushing's syndrome or hyperaldosteronism. All subjects had serum 17-OHP and cortisol responses measured at baseline and at 30 and 60 min following the intravenous administration of 250 micrograms of ACTH. Baseline 17-OHP levels in patients with adrenal nodules were not significantly different from those of the normal controls (adrenal nodules 17-OHP: 75 +/- 13 vs control 68 +/- 11 ng/dl). After stimulation with ACTH, both 30 min and 60 min 17-OHP levels in patients with adrenal nodules (322 +/- 47 and 361 +/- 54 ng/dl, respectively) were significantly elevated over the responses seen with the controls (169 +/- 29 ng/dl at 30 min, p < 0.015, and 158 +/- 20 ng/dl at 60 min, p < 0.004). Baseline and post-ACTH serum cortisol levels were similar in both groups. Out of these twelve patients with adrenal nodules, nine were reevaluated twelve months later. In this group the basal 17-OHP remained comparable to normal levels (72 +/- 8.4 ng/dl) whereas the post-ACTH levels still remained exaggerated (30 and 60 min values 327 +/- 37 and 373 +/- 39 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of hepatic congestion due to right heart failure mimicking liver tumor

This report describes a patient with hepatic congestion due to right heart failure mimicking liver tumor. The patient had a history of breast cancer and left total mastectomy 30 years ago, tricuspid valve regurgitation and tricuspid valve replacement 4 years ago. Three years ago, abdominal contrast-enhanced computed tomography (CT) was performed to evaluate inguinal hernia, which revealed multiple small hepatic nodules. After 1 year, the number and size of liver nodules were increased in CT scan. The patient underwent gun biopsy and histopathology revealed sinusoid enlargement. The patient recently had jaundice, abdominal distension, and peripheral edema. Liver dynamic CT scan was done to evaluate the palpable liver. The number and size of liver nodules were more increased in CT than 2 years ago. In magnetic resonance imaging (MRI), numerous variable sized ill-defined nodules replacing entire liver with progressing centripetal enhancement, which were suggestive of malignancy such as angiosarcoma, were noted. MRI finding suspects malignancy or hemangiosarcoma. Finally, the patient received repeated gun biopsy, and histopathology revealed findings compatible with hepatic congestion.     

Isolated splenic lymphoma: an elusive preoperative diagnosis.

Four patients underwent splenectomy for various clinical and radiological diagnoses and were found to have primary splenic lymphoma at surgery and histology. The diagnosis was classical Hodgkin's lymphoma, mixed cellularity type (one case); marginal zone B-cell non-Hodgkin's lymphoma (one case); and large B cell type non-Hodgkin's lymphoma (two cases). The first two patients had multiple nodules in the spleen measuring 0.1-0.5 cm while large cell lymphomas had large nodules (largest measuring 11 cm x 7 cm x 4 cm). The diagnoses were confirmed by immunohistochemical analysis. Mean follow up of these patients was 11 months; all patients received chemotherapy. One patient died, of causes not related to the disease process.     

Fine-needle aspiration of thyroid nodules in radiation-exposed patients.

External radiation used to treat benign conditions in the head and neck area results in an increased risk of thyroid cancer in exposed individuals. Fine-needle aspiration (FNA) biopsy is the standard procedure used to evaluate suspicious thyroid nodules. Its accuracy has been extensively studied, but little is known about FNA in irradiated patients. We analyzed the FNA experience of 136 irradiated subjects. Fifty-two had surgery enabling a comparison of the histologic diagnosis with the FNA results. In these 52 patients with a total of 53 FNAs, 20 were reported as benign, 14 as follicular neoplasms, 6 as papillary cancer, and 13 as inadequate samples. Seven malignant nodules were aspirated; 4 were reported as papillary cancer, 1 was reported as benign and 2 had inadequate specimens. An additional 11 patients had thyroid cancer in foci that were not subjected to FNA. For the nodules that were aspirated, and considering an FNA report of follicular neoplasm as a false-positive when a follicular adenoma or a colloid nodule was found at surgery, the calculated sensitivity was 80%, specificity 54%, positive predictive value 20%, and negative predictive value 95%. Of the 14 follicular neoplasm FNA diagnoses, 10 were colloid nodules (71%), and 4 only were follicular adenomas. We conclude that the sensitivity of FNA in irradiated patients is similar to what is reported for the general population. However, smaller malignant nodules are common and are not diagnosed by the FNA. Also, the FNA diagnosis of follicular neoplasm is often inaccurate and inadequate aspirations are frequent in this patient group.     

The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is a commonly performed procedure used in the evaluation of solitary thyroid nodules, in which the risk of malignancy is approximately 5% in most patients. Recently, the use of ultrasound (US) guidance in FNAB has been shown to enhance the diagnostic efficacy of this procedure. However, the risk of malignancy in thyroid nodules occurring within a multinodular goiter (MNG) has not been completely clarified, nor has the optimal means of investigating such nodules using FNAB. SUBJECTS AND METHODS: We performed a retrospective study of all patients seen over a 4-year period with a MNG that had one or more nodules who underwent FNAB under US guidance. The results from the history and physical examination, thyroid function and antibody tests, radionuclide studies, thyroid sonogram, cytology of aspirated nodules, and surgical pathology were recorded and analyzed. RESULTS: A total of 93 nodules were aspirated in 61 patients with MNG. Adequate material was obtained in 96% of aspirates on the first attempt. Sixty-seven aspirates in 44 patients yielded benign cytology and 22 aspirates in 15 patients yielded suspicious cytology. All patients with suspicious cytology underwent thyroid surgery. Thyroid cancer was found in 5 of these nodules, including 4 cases of papillary cancer and 1 case of Hürthle cell cancer, and 1 additional patient had occult papillary cancer discovered. The overall malignancy rate in thyroid nodules among the patients with MNG was approximately 5%. CONCLUSIONS: FNAB under US guidance is a useful diagnostic modality in the evaluation of thyroid nodules in selected patients with MNG. Because the risk of thyroid malignancy in these nodules is comparable to that which exists in solitary thyroid nodules, the possibility of thyroid malignancy should be considered in all patients with MNG.     

Studies on nodules and adult Onchocerca volvulus during a nodulectomy trial in hyperendemic villages in Liberia and Upper Volta. I. Palpable and impalpable onchocercomata

In hyperendemic onchocerciasis areas of West Africa nodulectomy trials were performed. 163 nodule carriers from four villages in the Liberian rain-forest and 52 nodule carriers from a savanna village in Upper Volta were operated on. During the surveys in the villages in Liberia and Upper Volta, an average of three and five nodules respectively per patient were palpated. Before each operation a further palpation was done and two more nodules per patient from both countries were found. The nodulectomies revealed 75% more nodules in the Liberian patients and 53% more in the patients from Upper Volta than were palpated immediately before. Half of these additional subcutaneous nodules extirpated in Liberians were superficially located, the other half deeper and impalpable through the skin. In the patients from Upper Volta two thirds of the additional nodules were seated in the depth of the subcutis. In both countries an average of three deep subcutaneous nodules per patient were found and this was equivalent to 20% of all extirpated onchocercomata. Most of these deep subcutaneous nodules were at those sites where most of the superficial nodules were located.     

Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans.

Direct gene transfer offers the potential to introduce DNA encoding therapeutic proteins to treat human disease. Previously, gene transfer in humans has been achieved by a cell-mediated ex vivo approach in which cells from the blood or tissue of patients are genetically modified in the laboratory and subsequently returned to the patient. To determine the feasibility and safety of directly transferring genes into humans, a clinical study was performed. The gene encoding a foreign major histocompatibility complex protein, HLA-B7, was introduced into HLA-B7-negative patients with advanced melanoma by injection of DNA-liposome complexes in an effort to demonstrate gene transfer, document recombinant gene expression, and determine the safety and potential toxicity of this therapy. Six courses of treatment were completed without complications in five HLA-B7-negative patients with stage IV melanoma. Plasmid DNA was detected within biopsies of treated tumor nodules 3-7 days after injection but was not found in the serum at any time by using the polymerase chain reaction. Recombinant HLA-B7 protein was demonstrated in tumor biopsy tissue in all five patients by immunochemistry, and immune responses to HLA-B7 and autologous tumors could be detected. No antibodies to DNA were detected in any patient. One patient demonstrated regression of injected nodules on two independent treatments, which was accompanied by regression at distant sites. These studies demonstrate the feasibility, safety, and therapeutic potential of direct gene transfer in humans.     

Gluteal nodules in patients with metastatic midgut carcinoid disease treated with depot somatostatin analogs

CONTEXT AND OBJECTIVES: We were referred a patient with metastatic well-differentiated endocrine tumor of the small intestine (midgut carcinoid) in whom asymptomatic sc gluteal nodules had been identified on routine abdominal computed tomography and labeled as metastases. This prompted us to assess the prevalence and cause of these nodules. DESIGN AND SETTING: This was a retrospective, cross-sectional study at a university teaching hospital. METHODS: Routine abdominal computed tomography scans of 56 patients with metastatic midgut carcinoid were analyzed by two independent radiologists, blinded to treatment status (depot somatostatin analogs). MAIN OUTCOME MEASURES: Number of patients with nodules, number of injections, and duration and total cumulative dose per patient were assessed. RESULTS: No nodules were detected in 13 patients not on depot somatostatin therapy. Nodules were found in 29 of 43 patients (67%) on somatostatin analog therapy: 16 of 22 patients on lanreotide Autogel, five of 12 patients on octreotide LAR only, and eight of nine patients who had been treated with both somatostatin analogs. There was no difference in the clinical state of those with or without nodules. Per patient, the average number was seven, and average size was 1 cm. Presence of nodules was significantly associated with total number of injections (P = 0.024), duration on treatment (P = 0.022), and cumulative dose of lanreotide Autogel (P < 0.001). Nodules underwent involution on follow-up imaging. CONCLUSION: Patients with metastatic midgut carcinoid tumors have large numbers of asymptomatic sc nodules in the gluteal area when on either depot somatostatin analog, but these resolve over time. This clear observation gives reassurance to patients and those managing them that such nodules are unlikely to represent metastases.