Mono- and oligoclonal immunoglobulin anomalies in kidney transplant patients

Serum from 115 HIV negative renal transplant recipients having more than 6 months follow-up was tested for the presence of mono- or oligoclonal immunoglobulins (moIg) by immunoelectrophoresis or immunofixation. Mono/oligoclonal gammapathy was detected in 16 patients (13.9%). Eight of these patients had only one monoclonal band, whereas the other eight had two or more bands. Thirteen of the 16 patients (81.3%) were IgG kappa positive, nine (56.3%) were IgG lambda positive, four (25.0%) were IgM lambda positive and only one (6.3%) was IgM kappa positive. Six monoclonal patients (37.5%) were IgG kappa positive and two monoclonal patients (12.5%) were IgG lambda positive. The oligoclonal combination IgG kappa lambda was present in three patients (18.8%), the combination IgG lambda + IgM lambda was present in two patients (12.5%) and IgG lambda + IgM lambda was present in one patient. The triple combination IgM kappa lambda + IgG kappa lambda and IgM lambda + IgG kappa lambda was found in two patients (12.5%). Ninety percent of these moIg did not exceed 2 g/L. MoIg appeared between 1 and 28 months after the kidney transplantation (mean value: 8.5 5.9 months) but were often transient, disappearing within 1 to 19 months in 13 patients (81.3%). Nine of the 16 cases (56.3%) disappeared before the end of the first year after detection. Risk factors for the appearance of these immunoglobulins have been identified as: the patient's age, the duration of haemodialysis, the occurrence of prior (anti-cytomegalovirus [CMV]) infection, and therapy with cyclosporin A (CsA). The persistence of monoclonal gammapathy was associated with acute or reactivated Epstein-Barr virus (EBV) infection and inability to convert IgM to IgG CMV antibodies. Furthermore, no association was established with previous hepatitis B or C infection or the number of rejection episodes. Kaposi's sarcoma was found in one patient (6.3%) but had no correlation with the presence of moIg. We recommend careful follow up of renal transplant patients in whom moIg have been discovered.     

Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity mimicking immune-complex glomerulonephritis

BACKGROUND: Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. METHODS: Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). RESULTS: The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1kappa, one IgG1lambda, one IgG2lambda, four IgG3kappa, and one IgG3lambda). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL, range 0.9 to 8.0), proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGkappa and two IgGlambda); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). CONCLUSION: Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.     

Malignant teratoma in the thyroid gland of an adult: a case report and a review of the literature

Teratomas in the neck are rare neoplasms. Most occur in the neonate and are benign. In contrast, cervical teratomas in adults are malignant and carry a poor prognosis. Fourteen adult cases have been reported in the world literature, and 11 of these were stated to have arisen in the thyroid gland. A case of a 27-year-old man who presented with a large goiter is reported. A preoperative diagnosis of a malignant thyroid mass was suggested by clinical examination, needle aspiration, and computerized tomography. The patient had a subtotal debulking thyroidectomy. The pathologic specimen confirmed a primary malignant teratoma of the thyroid gland. Despite a combination of radiotherapy and chemotherapy, which were well tolerated, the patient died 2 months after surgery.     

Primary neurilemoma of the thyroid gland: Report of a case

Neurilemoma, like other non-epithelial tumors, seldom occurs in the thyroid gland. A 57-year-old man was first referred to our hospital with an asymptomatic anterior neck tumor. A solid tumor was detected in the right lobe of the thyroid and an enucleation of the thyroid tumor was performed. The tumor was 35×33×33 mm in size, and diagnosed as Antoni A type neurilemoma. We were only able to find seven previously reported detailed cases of primary neurilemoma of the thyroid gland. A review of these cases, however, revealed that neurilemoma tends to develop in the right lobe of the thyroid gland. An operation is thus considered necessary and an enucleation of the tumor is appropriate.     

Synchronous primary triple cancers including the lung, stomach, and thyroid: a case report

A 62-year-old man with synchronous multiple primary cancers involving the lung, stomach, and thyroid was admitted. Initially the patient's chest X-ray showed an abnormal shadow in the right middle-lobe indicating lung cancer. During preoperative examination, gastric cancer of the antrum and angle were detected. Excisional biopsy of the lymph node in the neck after chest surgery revealed thyroid cancer. A middle lobectomy with mediastinal lymph node dissection was performed for lung cancer and the histological diagnosis was moderately differentiated adenocarcinoma, pT4N2M0, stage IIIB. Gastric cancer was treated by endoscopic mucosal resection. Considering the relatively better prognosis of papillary thyroid cancer, we concluded that no further treatment to the thyroid lesion was necessary. In Japan, according to autopsy reports, triple primary cancers are gradually increasing. During the periods 1994 to 1996, the incidence of triple cancers was 0.81% of all autopsy cases reported.     

Papillary microcarcinoma of the thyroid and secondary hyperparathyroidism in a patient on hemodialysis

Association between non-medullary thyroid carcinoma and secondary hyperparathyroidism have been rarely reported in patients with renal failure. A few cases of micropapillary thyroid carcinoma have been reported in patients before and after renal transplantation. We present a case of incidental detection of thyroid carcinoma at the time of parathyroidectomy in patient on dialysis after cadaver renal transplantation.     

Oral plasmablastic lymphoma in an HIV-negative patient: a case report and review of the literature.

Plasmablastic lymphoma is an HIV-associated non-Hodgkin's lymphoma that primarily affects the oral cavity and jaws. The purpose of this report is to describe the first case of plasmablastic lymphoma occurring in an HIV-negative, nonimmunocompromised individual, and to review the histopathologic and immunohistochemical phenotype of this lymphoma. Histopathologically, our case exhibited a dense, diffuse lymphocytic infiltrate of noncohesive large lymphocytes with plasmacytoid features. Immunohistochemical analysis revealed positivity for the B-cell marker CD79a, VS38c, Epstein-Barr virus latent membrane protein (LMP), immunoglobulin G (IgG), and lambda light chain restriction. Neoplastic cells were negative for leukocyte common antigen, CD20, CD3, CD10, CD138, Bcl-2, Bcl-6, desmin, actin, EMA, S-100, HMB45, Alk-1, HHV8, IgA, IgM, and cytokeratin. The features of this rare disease are summarized based on a comprehensive review of the epidemiologic, clinical and immunohistochemical findings of previously reported cases.     

Lambda-light-chain-mediated anti-GBM disease

A 77-year-old man presented with macroscopic haematuria and oligo-anuric renal failure. A renal biopsy showed moderate linear glomerular basement membrane (GBM) staining with lambda light chains alone, but both circulating IgG and lambda light chain activity were present. There was no evidence of a serum or urinary paraprotein and a bone marrow biopsy was normal. Serum lambda light chains did not bind to renal GBM when examined by indirect immunofluorescence. This case suggests that light chains are capable of binding directly to epitopes in the GBM and may initiate injury although by a different mechanism from the IgG anti-GBM molecule.     

Redefining Anatomy in a Case of Midline Subhyoid Ectopic Thyroid

Ectopic thyroid is an uncommon embryological aberration of the thyroid descent. Subhyoid median ectopic thyroid gland is a result of incomplete descent of the thyroid anlage and is characterized by a cosmetically unacceptable ovoid mass of thyroid tissue in the midline overlying the thyroid cartilage and thyrohyoid membrane. A normally placed thyroid gland is not detectable and in most cases all functioning thyroid tissue is located within the mass. Most of the ectopic thyroids are usually mistaken for a thyroglossal cyst and excised. Severe myxedema follows removal. Many cases have been reported in the literature, none of which was recognized prior to operation. All patients were operated upon for removal of a thyroglossal duct cyst. The diagnosis was missed at operation and in these cases severe myxedema was universal. The cause of the myxedema was not always immediately recognized. Therefore, many diagnostic tests including thyroid function test, ultrasound of the neck, and thyroid scanning had been recommended in the preoperative evaluation of a thyroglossal cyst. Here, we present a case of ectopic thyroid mass which was the only thyroid tissue present in the neck. So, division and repositioning of the thyroid mass thereby redefining the anatomy was done with good cosmetic results.     

Unifocal autonomy and carcinoma of the thyroid gland]

Two cases operated upon with the clinical diagnosis of unifocal autonomous functioning thyroid nodules (AFTN) are reported where the histological diagnosis revealed a well differentiated thyroid carcinoma (follicular, papillary) without metastasis. The pathogenesis of differentiated thyroid carcinomas in cases of AFTN may be coincident. Alternatively it may evolve from thyroid epithelial cells of the hot nodule, resulting in a "hot" well differentiated thyroid carcinoma. These cases show that under the clinical diagnosis of AFTN a differentiated thyroid carcinoma can be hidden occasionally.     

Renal cell carcinoma with metastasis to the thyroid gland

Cancers that metastasize to the thyroid gland are uncommon. Metastasis to the thyroid gland has been reported in renal cell carcinoma (RCC), breast cancer, lung cancer, gastrointestinal malignancies, malignant melanoma, sarcoma, hematologic malignancies, and other genitourinary cancers. A computer search of the records of the department of pathology at Loyola University Medical Center was done to determine the number of thyroidectomies performed between 1988 and 1998. A detailed review of the clinical records of patients with metastasis to the thyroid gland from RCC was done. A total of 941 thyroidectomies were performed between 1988 and 1998. Metastasis to the thyroid gland was seen in six cases (0.64%). Three of these six cases had metastasis from RCC. The interval between the diagnosis of the primary RCC and the thyroid metastasis was 2 to 10 years. Two of these three patients had an adenomatous thyroid gland. Metastases to the thyroid, though relatively rarely diagnosed clinically as a cause of thyroid nodule, must be considered in the differential diagnosis of thyroid nodule, particularly in patients who have a history of RCC.     

How to treat a thyroid adenocarcinoma inside a branchial cyst

The authors reported three cases of branchial cycts containing a thyroid adenocarcinoma. This rare condition imposed a search for the primary tumor. All complementary investigations remained negative as in the few cases reported in the medical literature. A loboisthmectomy for one and a total thyroidectomy for the two others, with cervical recurential neck dissection for all was carried out. Histological examination of the operative specimen after total blocking in paraffin helped discover microscopic foci of papillary carcinoma in the thyroid gland. These data justified this therapeutic attitude because the nature of the adenocarcinoma found in the branchial cyst is likely to be metastatic.     

Primary osteosarcoma of the thyroid gland]

Primary extraosseous osteosarcoma of the thyroid gland is a very rare tumor with a poor prognosis. Only few cases have been reported in the literature. Metastases of osteosarcoma in the thyroid gland were also found but are very seldom. A primary thyroid tumor with osteosarcomatous differentiation in a 82-year-old man is presented and the histopathological classification, biological features and possible mechanisms of the occurrence of such thyroid tumors are briefly discussed.     

Hemiaplasia of the thyroid associated with Graves' disease: Report of three cases and a review of the literature

We recently treated three additional patients with hemiaplasia of the thyroid associated with Graves' disease, making a total of eight such cases. All eight of these patients were women and their chief complaints were goiter in five cases, whereas exophthalmos or palpebral edema were noted in six cases. All eight patients underwent surgery for Graves' disease. The left lobe was absent in six cases and the right lobe in two, whereas the isthmus was absent in six cases and the pyramidal lobe in four. A total of 102 cases of hemiaplasia of the thyroid, including our present three cases, have been reported in the world literature since 1970, with 32 of them consisting of hemiaplasia associated with hyperthyroidism. Of these, the cause of hyperthyroidism was Graves' disease in 22 cases, an autonomously functioning thyroid nodule in 7, and thyrotoxic multinodular goiter in 3. The left lobe was absent in 19 cases while the right lobe was missing in 12, and laterality was unknown in 1 case.     

Prediction of malignancy in the solitary thyroid nodule by physical examination, thyroid scan, fine-needle biopsy and serum thyroglobulin. A prospective study of 100 surgically treated patients

A prospective study was made of 100 consecutive patients selected for surgical treatment of a clinically solitary thyroid nodule. Anamnestic data and findings at physical examination, thyroid scan, fine-needle aspiration biopsy and measurement of serum thyroglobulin were correlated with the postoperative histologic diagnoses. The histologic findings were malignant in 18 cases and benign in 82. Familial occurrence of benign goiter was reported more frequently by patients with benign than by those with malignant histology (46 and 11%). Of the 11 nodules that were hard at palpation, 7 were malignant. All 12 scintigraphically "hot" nodules were benign, but 13 of 59 "solitary, cold" nodules were malignant. The cytologic specimens were reviewed and reclassified. The needle aspirate was insufficient for cytologic diagnosis in 11 cases. Papillary carcinoma was cytologically recognized in four cases. Of 36 lesions cytologically reported to be neoplasm of unspecified type, 12 were histologically shown to be malignant, 20 were follicular adenomas and 4 were colloid goiter. Benign lesion was the cytologic diagnosis in 47 cases. One diagnosis was false negative, but the cancer lay beneath the index nodule. The thyroglobulin level was significantly higher in patients with thyroid cancer than in those with benign disorders, but the test's predictive value was low. Thyroglobulin levels more than tenfold the upper limit of normal were found only in three patients with thyroid cancer and two with thyrotoxicosis. Although all of the mentioned investigative data were helpful in the management of solitary thyroid nodule, fine-needle biopsy was the best single method. When cytologic examination shows malignancy or unspecified neoplasm, surgery is indicated. For most patients with cytologically benign lesions, careful follow-up will suffice.     

Papillary carcinoma of the thyroid arising on thyroglossal duct cysts: report of a case and review of the literature

Thyroglossal duct cysts are the most common congenital disorder of the neck. One percent of cases may degenerate and give rise to a cancer, mainly arising in the pericystic thyroid tissue. Some 250 cases have been reported in the literature to date. We report here on a 39-year-old man with a midline mass in the neck measuring 4 cm max. The patient was examined preoperatively by ultrasonography of the neck and assay of thyroid hormones, which yielded a diagnosis of a thyroglossal duct cyst. On the basis of these findings, the patient underwent surgery to remove the mass and, after an extempore histopathological examination, was submitted to total thyroidectomy owing to the presence of papillary carcinoma of the thyroid arising on the thyroglossal duct cyst with multiple foci in the context of the thyroid gland. Most thyroid cancers at the time of surgery are confined to the thyroid gland, infiltrating the adjacent structures in approximately 20% of cases and the local-regional lymph nodes in 8 to 11.5%. Thyroid papillary adenocarcinoma is multifocal in 21% of cases. The multifocal nature of the cancer makes total thyroidectomy mandatory at the same time as surgery is performed to remove the cyst.     

甲状腺微小癌（附71例报告）

目的 探讨甲状腺微小癌诊断和外科治疗的经验。方法 总结１９８５年１月至１９９８年８月间经手术和病理证实的甲状腺微小癌７１例,结果 仅有５例术前诊断微小工由病理证实３例出现颈淋巴结转移,１例骨转移,２６例行一侧腺叶全切除加对侧次全切除术,３例加颈淋巴结清扫术,其余行一侧腺叶全切除和一侧或两侧腺叶次全切除,随访病例中,术后复发１例（１．６％）,无一例死亡,结论 甲状腺微小癌发生率较高,提高术术,术中的     

Primary neurilemmoma of the thyroid gland in a 12-year-old girl

A case of a neurilemmoma of the thyroid gland in a 12-year-old girl is reported. The tumor was noted as a asymptomatic left lower neck swelling 9 months before admission. Ultrasound scan showed the solid lesion of predominantly hypoechoic structure measuring 17.2 × 12 × 26 mm within the left lobe. Pathologic examination of the excised lobe was consistent with neurilemmoma with both Antoni A and Antoni B histologic patterns. To date only 14 cases of this nonepithelial tumor of the thyroid gland have been described in the literature, and all occurred in adult patients. This is the first report of thyroid neurilemmoma in a child.     

Encapsulated papillary oncocytic neoplasms of the thyroid: morphologic, immunohistochemical, and molecular analysis of 18 cases

Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.     

Papillary carcinoma of the thyroglossal duct cyst: a case report

The thyroglossal duct cyst is the most common anomaly in thyroid development. To date, approximately 250 cases have been reported, the majority being papillary thyroid carcinomas. In most cases the diagnosis is established only after excision of a clinically benign thyroglossal duct cyst. Controversies exist in relation to a rational and effective therapeutic approach. A further case of thyroglossal duct papillary carcinoma affecting a 52 years-old man is presented to highlight the clinicopathological features of this condition. FNAC resulted false negative. Surgery consisted in a Sistrunk procedure, followed by total thyroidectomy and central lymphectomy after definitive histological diagnosis. In view of the prolonged course of papillary carcinoma, long-term follow-up is mandatory.