Patient Demographics > Country of Treatment > Greece
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Summary
Struma ovarii is an ovarian teratoma that comprises 2–5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (131I) therapy.
Learning points
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Malignant transformation of struma ovarii is very rare (<5%).
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Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue.
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There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions.
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TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.
Search for other papers by Evangelos Karvounis in
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Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
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Search for other papers by Christos Panopoulos in
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Summary
Large-cell neuroendocrine carcinoma (LCNEC) is a rare neuroendocrine prostatic malignancy. It usually arises after androgen deprivation therapy (ADT), while de novo cases are even more infrequent, with only six cases described. The patient was a 78-year-old man with no history of ADT who presented with cervical lymphadenopathy. Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations. Results showed a poorly differentiated carcinoma in the thyroid gland accompanied by cervical lymph node enlargement. Thyroid surgery revealed LCNEC metastasis to the thyroid gland. Additional metastases were identified in both the adrenal glands. Despite appropriate treatment, the patient died of the disease. De novo LCNEC of the prostate is a rare, highly aggressive tumor with a poor prognosis. It is resistant to most therapeutic agents, has a high metastatic potential, and is usually diagnosed at an advanced stage. Further studies are required to characterize this tumor.
Learning points
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De novo LCNECs of the prostate gland can metastasize almost anywhere in the body, including the thyroid and adrenal glands.
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LCNECs of the prostate are usually associated with androgen-depriving therapy, but de novo cases are also notable and should be accounted for.
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Further studies are required to fully understand and treat LCNECs more effectively.
Search for other papers by Nikitas S Skarakis in
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Search for other papers by Irene Papadimitriou in
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Summary
Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided.
Learning points
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Juxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension.
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JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications.
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Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT.
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For the confirmation of the diagnosis, a histopathologic examination is needed.
Search for other papers by Paraskevi Kazakou in
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Summary
Medullary thyroid carcinoma (MTC) has a varying clinical course; distant metastases are frequently present even at diagnosis. We present two MTC cases with unusual metastatic sites. Two female patients are presented with slow progressive MTC. The first case developed distant metastases 23 years after diagnosis and underwent locoregional therapies. At the same time a breast mass developed representing MTC metastasis. Treatment with vandetanib led to long-term disease stabilization. The second patient is presented with metastases in the pancreas 13 years after diagnosis. Shortly, a painful mass developed in the mandible and metastasis of MTC was diagnosed. Disease progression was recorded 20 months after the initiation of local and systemic therapy. Such cases have only rarely been reported in the literature and highlight the need for prompt recognition of unexpected MTC metastases.
Learning points
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Unusual sites of metastasis may appear in patients with medullary thyroid carcinoma (MTC) years after the initial diagnosis.
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Although rare, unexpected MTC metastases highlight the need for prompt recognition and appropriate treatment.
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Local recurrences accompanied by inappropriately low calcitonin levels should prompt further investigation for possible distant metastatic disease.
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Systemic treatment with tyrosine kinase inhibitors may be effective even in patients with unusual metastases from MTC.
Search for other papers by Michail Katsamakas in
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Summary
We present two cases of thyroid sarcoidosis that were misdiagnosed as thyroid cancer. In the first patient, fine needle aspiration cytology (FNAc) of a suspicious thyroid nodule indicated the presence of papillary thyroid cancer, and the patient underwent thyroid surgery. However, histopathology identified a sarcoid granuloma, without any sign of malignancy. The second patient had a history of papillary microcarcinoma with suspicious lymph nodes diagnosed years after the initial diagnosis and was referred for assessment of cervical lymphadenopathy. Fine needle aspiration cytology (FNAc) of the suspicious lymph nodes erroneously indicated metastasis from thyroid cancer, and lateral modified lymph node dissection was performed, based on FNAc and ultrasonographic features. Histopathology excluded malignancy and identified non-caseating granulomas. Sarcoidosis of the thyroid may have a clinical presentation similar to well-differentiated thyroid carcinoma and, although rare, should be considered in the differential diagnosis, especially when other signs of the disease are already present. In these cases, FNAc provided a false diagnosis of papillary thyroid carcinoma and lymph node metastases that led to unnecessary surgery.
Learning points
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Sarcoidosis may share clinical and ultrasonographic features with papillary thyroid carcinoma.
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Fine needle aspiration cytology is helpful in the diagnosis of both conditions; however, the overlapping cytological characteristics may lead to erroneous diagnosis.
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The present cases illustrate the importance of cytological identification of these difficult cases. Every piece of information provided by the clinician is essential to the cytologist.
Search for other papers by S Livadas in
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Summary
HAIR-AN syndrome, the coexistence of Hirsutism, Insulin Resistance (IR) and Acanthosis Nigricans, constitutes a rare nosologic entity. It is characterized from clinical and biochemical hyperandrogenism accompanied with severe insulin resistance, chronic anovulation and metabolic abnormalities. Literally, HAIR-AN represents an extreme case of polycystic ovary syndrome (PCOS). In everyday practice, the management of HAIR-AN constitutes a therapeutic challenge with the available pharmaceutical agents. Specifically, the degree of IR cannot be significantly ameliorated with metformin administration, whereas oral contraceptives chronic administration is associated with worsening of metabolic profile. Liraglutide and exenatide, in combination with metformin, have been introduced in the management of significantly obese women with PCOS with satisfactory results. Based on this notion, we prescribed liraglutide in five women with HAIR-AN. In all participants a significant improvement regarding the degree of IR, fat depositions, androgen levels and the pattern of menstrual cycle was observed, with minimal weight loss. Furthermore, one woman became pregnant during liraglutide treatment giving birth to a healthy child. Accordingly, we conclude that liraglutide constitutes an effective alternative in the management of women with HAIR-AN.
Learning points:
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HAIR-AN management is challenging and classic therapeutic regimens are ineffective.
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Literally HAIR-AN syndrome, the coexistence of Hirsutism, Insulin Resistance and Acanthosis Nigricans, represents an extreme case of polycystic ovary syndrome.
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In cases of HAIR-AN, liraglutide constitutes an effective and safe choice.
Search for other papers by Maria P Yavropoulou in
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Summary
Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology.
Learning points:
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We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A.
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Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling.
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GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.
Search for other papers by Maria P Yavropoulou in
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Search for other papers by Pantelis Zebekakis in
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Summary
Tumor-induced osteomalacia (TIO) is a rare form of hypophosphatemia usually caused by phosphaturic mesenchymal tumors (PMTs); the biologic behavior of PMTs is under investigation. Herein we present a case of TIO with a protracted course over 12 years leading to a fatal outcome. A 39-year-old man presented with weakness in 2004 and was found to have decreased serum phosphorus, phosphaturia and low levels of 1,25-dihydroxyvitamin D3. Four years later he developed a painful left calf mass. The lesion was resected, but recurred causing extreme pain and dysfunction. Radiological examination showed a large cluster of soft tissue tumors affecting all the muscle compartments of the calf and a smaller lesion inside the metaphysis of the tibia. Above-knee amputation was performed. Histological examination of all lesions showed a cellular spindle cell neoplasm with variously sized vessels, wide vessel-like spaces and scattered deposits of calcified extracellular material. The tumor infiltrated skeletal muscles, subcutaneous fat and the proximal end of the fibula. The tibial lesion had identical histology. Three years after the amputation the patient presented with cough and dyspnea. Radiological examination, followed by an open biopsy, showed that there were multiple metastatic nodules of PMTs in both lungs. Shortly after the diagnosis the patient died. This case illustrates that even benign cases of PMTs may lead to a fatal outcome and the classification of PMTs into benign and malignant should be reassessed in order to correspond to its biological behavior.
Learning points:
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PMTs, aside from having locally aggressive behavior, may metastasize and cause death
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PMTs may behave aggressively despite ‘benign’ histological findings
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Accurate diagnosis of tumor-induced osteomalacia and patient management require a multidisciplinary approach
Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
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Msc Metabolic Bone Diseases, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
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Search for other papers by Helen Gogas in
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Summary
Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.
Learning points:
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Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.
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Breast cancer has the highest prevalence of hypercalcemia.
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The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).
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In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.
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Summary
Parathyroid carcinoma is an extremely rare endocrine malignancy that accounts for less than 1% of cases of primary hyperparathyroidism. We report a 44-year-old woman who presented with fatigue and diffuse bone pain. Laboratory findings revealed highly elevated serum calcium and parathyroid hormone (PTH) levels and a 4.5 × 3 × 2.5 cm cystic lesion in the lower pole of the right thyroid lobe that was shown histologically to be a parathyroid carcinoma. Ten years later, the patient developed brain and pulmonary metastases and recurrence of PTH-related hypercalcemia. Treatment of hypercalcemia along with localized radiotherapy and various chemotherapy regimens failed to induce a biochemical or radiological response. In conclusion, parathyroid carcinoma is a rare neoplasia that may develop metastases even after prolonged follow-up, for which there is no evidence-based treatment besides surgery. Different chemotherapeutic schemes did not prove to be of any benefit in our case highlighting the need for registering such patients to better understand tumor biology and develop specific treatment.
Learning points:
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Metastases can develop many years after parathyroid cancer diagnosis.
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Surgery is the only curative treatment for parathyroid carcinoma.
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Chemotherapy and radiotherapy prove to be ineffective in parathyroid cancer treatment.
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Patient registering is required in order to delineate underlining pathology and offer specific treatment.
