A 53-year-old female (gravida1, para1), presented to the Department of Nephrology due to thirsty, polydipsia, polyuria and gradually developing swelling of the limbs and face for more than one month. Medical history was notable for two months of lumbago, along with radiating pain to both lower extremities, which had been diagnosed as lumbar disc herniation, with ibuprofen ineffective to relieve the symptom. Personal and family history were otherwise unremarkable. On examination, she had edema of face and both lower limbs. High blood pressure (173/104 mmHg) was found while other vital signs were within normal ranges. Initial laboratory and ultrasound findings indicated acute kidney injury (AKI) (serum creatinine 157 umol/L; blood urea nitrogen 22.6 mmol/L; no significant increase in the size of the kidneys and cortical thickness), and drug-induced interstitial nephritis was presumed.
Nevertheless, after admission, profound hypercalcemia (Calcium: 4.47 mmol/L, N 2.10–2.55 mmol/L) and elevated level of PTH (280.1 pg/mL, N 12.0–88.0 pg/mL) suggested that the cause of AKI was dehydration from Hypercalcemic crisis. Hemodialysis was performed immediately, followed with intravenous fluids, diuresis, salmon calcitonin and pamidronate disodium. After symptomatic treatment, her blood pressure dropped back to normal with renal function recovery (serum creatinine 72 umol/L, blood urea nitrogen 7.4 mmol/L). However, recurrent symptoms, hypercalcemia and gradually increased level of PTH (280.1 pg/ml-486.0 pg/ml-1316.0 pg/ml) raised the possible diagnosis of primary hyperparathyroidism (PHPT). Upon further examination, neck ultrasound, Tc99m methoxyisobutylisonitrile (Tc99m-MIBI) scintigraphy scanning and chest computerized tomography all failed to localize a possible primary/ectopic parathyroid adenoma or hyperplasia lesion. The patient was transferred to Endocrinology Department due to unexplained hypercalcemia and hyperparathyroidism.
Further neck and chest 18F-fluorocholine positron emission tomography-computed tomography (18F-FCH PET/CT) still failed to identify specific overactive PTH secretion areas. Simultaneously, bone metabolic indexes such as serum osteocalcin (33.67 ng/ml) and total Procollagen Type I N-terminal Propeptide (77.69 ng/ml) indicated the existence of osteolytic destruction. Given the results above, endocrinologists got down to the possibility of ectopic PTH-secreting tumor and re-reviewed the medical history in detail: 1. left hip joint post-activity pain for more than two months; 2. perimenopause woman with menstrual disorder for nearly one year. Accordingly, hip X-ray was performed and revealed bone destruction of left ischium and inferior ramus of pubis. Transvaginal ultrasonography showed the intrauterine abnormal echo. The attention was finally attached to osseous metastatic tumor of gynecologic origin. Abdominopelvic magnetic resonance imaging (MRI) showed crumby-structured thickened endometrium and a 7 cm × 5 cm mass in the left ischium and pubis, both heterogeneously enhanced with obscure boundary, accorded with the manifestation of endometrial malignant tumor metastasizing to left obturator, also consistent with 18F-fluorodeoxyglucose PET/CT scan findings (Fig. 1). Nevertheless, subsequent colposcopy and directed biopsy of the cauliflower-like neoplasm at the external orifice of cervix revealed endometrial adenocarcinoma.
After multi-disciplinary team consultation, PHPT was excluded. Bone metastases of gynecologic tumor and ectopic secretion of PTH were thought to work together and lead to refractory hypercalcemia. However, the source of PTH was still inconclusive since endometrial adenocarcinoma is a nonendocrine tumor, with no relevant case reported so far. Definite diagnosis still remained pending.
Although it was hard to explain the relationship between the tumor feature and PTH secretion, initial chemotherapy was recommended due to the advanced disease. One week after the initiation of chemotherapy with nedaplatin (100 mg/m2) and paclitaxel (175 mg/m2), the patient’s pain resolved, her high serum calcium and PTH levels gradually dropped back to normal (Calcium: 2.37 mmol/L, PTH: 89.7 pg/ml) and remained within the normal limits during treatment (six months). Following two cycles of chemotherapy, the enlarged uterus and tumor were evaluated (physical examination and MRI) to be reduced partially. Palliative surgery of hysterectomy and bilateral salpingo-oophorectomy was recommended through multidisciplinary approaches and performed because of persistent vaginal spotting.
Intraoperative exploration revealed slightly enlarged irregular uterus with several subserous grey-white lesions involving the anterior-fundal wall, about 0.3cm-1cm in diameter. Dense adhesion of left infundibulopelvic ligament and sigmoid colon extended to left pelvic wall. No obvious abnormality was found in bilateral adnexa, omentum and bowel. Gross findings showed diffuse grey-white cauliflower-like lesions in the uterine cavity, 1–2 cm in size, with whole myometrial infiltration to the serosa layer. Whereas a polypoid neoplasm of about 3cm × 3cm × 2cm located in the upper endocervical canal was noted, with the gross appearance completely different from that of the uterine body. Post-operative pathology confirmed two distinct histologic types: endometrioid carcinoma and large cell neuroendocrine carcinoma (LCNEC), which were markedly different both visually and microscopically (Fig. 2). The diagnosis of LCNEC was supported by immunostaining for neural cell adhesion molecule (CD56), synaptophysin (Syn) and Chromogranin A (CgA). Deep myometrial and lymphavascular invasion were observed in LCNEC but not in endometroid carcinoma. Additionally, differential distribution of estrogen receptor (ER) and progesterone receptor (PR) between LCNEC (stromal) and endometroid carcinoma (glandular) was observed. To explore the reason of hypercalcemia and elevated PTH level, immunohistochemistry (IHC) staining was performed, and positive expression of PTH and PTH-related protein (PTH-rP) was detected in LCNEC other than in endometroid carcinoma (Fig. 2). Despite postoperative adjuvant chemotherapy and radiotherapy, the patient succumbed to the disease 12 months after diagnosis from recurrent hypercalcemia.
Literature review
In the systematic literature search of PubMed database using the search terms ((‘endometrium’[All Fields] OR ‘uterine’[All Fields]) AND ‘neuroendocrine carcinoma’[All Fields]), 539 citations were initially obtained (final search date 2020-12-01). After excluding literatures irrelevant or lacking of essential clinicopathological information, a total of 30 English language articles were identified eligible[1–30]. As shown in Table 1, more than 85% of endometrial LCNEC occurred in patients over 50 years, with a median age of 58 years (range 37 years ~ 88 years), which mostly appeared as abnormal bleeding and abdominal pain, similar to the presentation of other uterine carcinomas. Less common symptoms including dyspnea and dizziness caused by metastasis[17]. Except for a patient with psychosis caused by anti-N-methyl-d-aspartate receptor encephalitis[20], none of them presented as paraneoplastic syndrome. This type of aggressive malignancy is often diagnosed at advanced stage, with more than 70% of patients suffering wide metastasis. Of the 55 cases reported, preoperative diagnosis was achieved in only 4 cases[5, 12, 21, 28], since the pathological patterns based on small biopsy specimens were insufficient. In addition, the radiologic findings were nonspecific[12] and there is no NEC specific biomarkers[3]. Due to the resemblance of pathologic morphology features between LCNEC and other poorly-differentiated carcinoma, undifferentiated sarcoma and MMMT[1], postoperative immunohistochemistry based on a larger specimen serves as the most useful method for diagnosis, with at least one positive neuroendocrine marker detected in previous reported cases. LCNEC appeared simultaneously with other histological types at times, most frequently with endometrioid carcinoma (22 cases, 40%), followed by small-cell neuroendocrine carcinoma (7 cases, 12.7%) and serous carcinoma (4 cases, 7.3%). Relatively rare mixed histologic components including clear cell carcinoma[17], MMMT[1] and low-grade endometrial stromal sarcoma[29]. LCNEC tends to be aggressive and have strong propensity for metastasis[1]. Some patients with combined components of malignancies exhibited only distant LCNEC metastasis[8, 16]. Standard management has not been established due to its rarity, so is has been treated in the same way as other endometrial carcinoma. Except for 3 terminal-stage patients who accepted palliative care, most patients received surgery with or without adjuvant therapy. Hysterectomy and bilateral salpingo-ophorectomy were performed at minimum. Further procedures included lymphadenectomy, omentectomy, tumor cytoreduction and appendectomy. As for adjuvant therapy, 33 (60%) patients received chemotherapy, 18 (32.7%) patients combined with radiotherapy, and 6 (10.9%) patients received radiotherapy only. Chemotherapy regimen was available for 18 patients, and platinum in combination with etoposide, irinotecan or paclitaxel were generally used. However, despite the multi-modality approach of treatment, the prognosis is still poor. Of the 55 cases reported, more than half of the patients experienced recurrence or progression in 2 years. 25 cases progressed rapidly with a survival of less than 2 years, even in 5 patients with early-stage disease.
Table 1
Clinicopathologic features of currently reported uterine LCNEC
Case
|
Author
|
Age
|
FIGO
Stage
|
Presenting complaint
|
Biopsy pathology
|
Surgery
|
Postoperative pathology
|
Neuronal Markers
|
Adjuvant treatment
|
Outcome (months)
|
1
|
Erhan et al.
|
52
|
IC
|
AUB
|
NA
|
HystBSO
|
LCNEC
|
Syn, NSE
|
CT (EPcis) + RT
|
Recurrence (6), DOD (10)
|
2
|
Mulvany et al.
|
50
|
IIIC
|
AUB
|
NA
|
HystBSO, OMY, LND
|
LCNEC
|
Syn, NSE
|
CCRT (EPcar)
|
AWD (12)
|
3
|
Mulvany et al.
|
80
|
IC
|
AUB
|
NA
|
HystBSO, LND
|
LCNEC, EC G3
|
CgA, NSE
|
None
|
DOD (5)
|
4
|
Mulvany et al.
|
77
|
IIB
|
AUB
|
NA
|
HystBSO
|
LCNEC, EC G1
|
Syn, CgA, CD56, NSE
|
RT
|
DOD (23)
|
5
|
Mulvany et al.
|
79
|
IIIA
|
AUB
|
NA
|
HystBSO, Obx, Pbx
|
LCNEC, EC G1
|
CgA, CD56, NSE
|
RT
|
AWD (2)
|
6
|
Mulvany et al.
|
88
|
IIIC
|
AUB
|
NA
|
HystBSO, LND
|
LCNEC, EC G3, SCNEC with squamous differentiation
|
CgA, CD56, NSE
|
RT
|
AWD (1)
|
7
|
Posligua et al.
|
59
|
IIIB
|
AGC
|
High-grade NEC
|
Modified radical HystBSO, OMY, LND
|
LCNEC, papillary SC
|
Syn, CD56, NSE
|
CT (NA) + RT
|
AWD (5)
|
8
|
Albores-Saavedra et al.
|
42
|
IC
|
AUB
|
None
|
Radical hysterectomy
|
LCNEC
|
Syn, CgA, CD56
|
CT (EPcis)
|
NED (9)
|
9
|
Froio et al.
|
58
|
IB
|
AUB
|
Cancer of mesodermal origin
|
HystBSO, LND
|
Carcinosarcoma with LCNEC histology
|
Syn, CgA
|
None
|
Recurrence (6), NED (23)
|
10
|
Terada et al.
|
40
|
IB
|
AUB
|
Sarcomatous, undifferentiated carcinoma
|
HystBSO, LND, OMY
|
LCNEC with sarcomatous changes
|
Syn, CD56
|
CT (NA)
|
AWD (16)
|
11
|
Deodhar et al.
|
70
|
IB
|
AUB, abdominal pain
|
None
|
HystBSO, OMY
|
LCNEC
|
Syn, CgA, CD56
|
CT (EPcis)
|
Recurrence (3), NED (6)
|
12
|
Shahabi et al.
|
59
|
IIIC2
|
AUB
|
Poorly differentiated endometrial carcinoma
|
HystBSO, OMY,LND, APPY, tumor cytoreduction
|
LCNEC
|
Syn, CgA, CD56, NSE
|
Sandwich chemoradiotherapy (TC)
|
DOD (12)
|
13
|
Makihara et al.
|
73
|
IVB
|
Lumbago,abdominal distention
|
LCNEC
|
None
|
None
|
Syn, CgA, NSE
|
Palliative care
|
DOD (1)
|
14
|
Makihara et al.
|
73
|
IIIC
|
AUB, heavy discharge
|
Adenocarcinoma with solid poorly differentiated component
|
HystBSO, OMY, LND
|
LCNEC
|
Syn, CgA, CD56
|
CT (IP)
|
Recurrence (13)
|
15
|
Nguyen et al.
|
71
|
IVB
|
AUB
|
Extensive necrosis and apoptosis
|
Radical HystBSO, OMY, LND, tumor cytoreduction
|
LCNEC
|
Syn, CgA, CD56
|
None
|
DOD (1)
|
16
|
Chougule et al.
|
55
|
IB
|
AUB
|
Moderately differentiated adenocarcinoma
|
HystBSO, LND
|
LCNEC
|
Syn, CgA, CD56
|
None
|
NA
|
17
|
Konishi et al.
|
54
|
IIIC1
|
AUB
|
Poorly differentiated endometrial carcinoma
|
Modified radical HystBSO, LND, OMY
|
LCNEC
|
Syn, CgA, CD56
|
CT (IP)
|
Recurrence (3)
|
18
|
Matsumoto et al.
|
51
|
IIIA
|
Cancer screening
|
Adenosquamous carcinoma with neuroendocrine differentiation
|
Radical HystBSO, OMY, LND
|
LCNEC, EC G1
|
Syn, CgA, CD56
|
CT (IP)
|
NED (20)
|
19
|
Ono et al.
|
41
|
II
|
Vaginal mass
|
None
|
Hysterectomy
|
LCNEC, EC G3
|
Syn, CgA, CD56
|
CT (TC)
|
Recurrence (24), NED (103)
|
20
|
Pocrnich et al.
|
54
|
IA
|
NA
|
NA
|
HystBSO
|
LCNEC
|
CgA
|
RT
|
NED (96)
|
21
|
Pocrnich et al.
|
65
|
IA
|
AUB
|
NA
|
HystBSO,LND
|
LCNEC, SCNEC, EC G3
|
Syn, CgA, CD56
|
RT
|
DOD (9)
|
22
|
Pocrnich et al.
|
84
|
IB
|
AUB, abnormal Pap smear
|
NA
|
HystBSO,LND
|
LCNEC, EC G2
|
CD56
|
RT
|
NED (118)
|
23
|
Pocrnich et al.
|
66
|
IB
|
AUB
|
NA
|
HystBSO,LND
|
LCNEC, EC G2
|
Syn
|
CT (NA) + RT
|
Recurrences (8), NED (37)
|
24
|
Pocrnich et al.
|
55
|
IB
|
AUB
|
NA
|
HystBSO
|
LCNEC, EC G2
|
Syn, CgA
|
NA
|
NA
|
25
|
Pocrnich et al.
|
47
|
II
|
AUB
|
NA
|
HystBSO,LND
|
LCNEC, EC G2
|
Syn, CgA
|
CT (NA) + RT
|
DOD (15)
|
26
|
Pocrnich et al.
|
51
|
II
|
AUB, abnormal Pap smear
|
NA
|
HystBSO,LND༌Obx
|
LCNEC, EC G2
|
Syn, CgA
|
CT (NA) + RT
|
AWD (11)
|
27
|
Pocrnich et al.
|
68
|
IIIA
|
AUB
|
NA
|
HystBSO
|
LCNEC, SCNEC, EC G2
|
Syn, CgA, CD56
|
CT (NA) + RT
|
NED (24)
|
28
|
Pocrnich et al.
|
69
|
IIIA
|
AUB
|
NA
|
HystBSO,LND
|
LCNEC
|
CgA
|
CT (NA) + RT
|
NED (5)
|
29
|
Pocrnich et al.
|
59
|
IIIB
|
Abnormal Pap smear
|
NA
|
HystBSO,LND
|
LCNEC, SC
|
Syn, CD56
|
CT (NA) + RT
|
NED (92)
|
30
|
Pocrnich et al.
|
54
|
IIIB
|
AUB
|
NA
|
HystBSO,LND
|
LCNEC, EC G2
|
Syn, CgA
|
CT (NA) + RT
|
NED (134)
|
31
|
Pocrnich et al.
|
68
|
IIIB
|
AUB
|
NA
|
HystBSO, LND, APPY
|
LCNEC, SCNEC, EC G3, clear cell carcinoma
|
Syn
|
CT (NA) + RT
|
DOD (13)
|
32
|
Pocrnich et al.
|
52
|
IIIC1
|
AUB
|
NA
|
HystBSO, LND
|
LCNEC
|
CgA
|
CT (NA) + RT
|
Recurrence(25), NED (66)
|
33
|
Pocrnich et al.
|
55
|
IIIC2
|
AUB
|
NA
|
HystBSO, LND
|
LCNEC
|
Syn, CD56
|
None
|
DOD (6)
|
34
|
Pocrnich et al.
|
63
|
IIIC2
|
NA
|
NA
|
HystBSO, LND, Obx
|
LCNEC
|
Syn, CgA, CD56
|
NA
|
NA
|
35
|
Pocrnich et al.
|
87
|
IVB
|
AUB
|
NA
|
HystBSO, Obx
|
LCNEC, SCNEC, EC G3
|
Syn
|
CT (NA)
|
DOD (21)
|
36
|
Pocrnich et al.
|
59
|
IVB
|
Dizziness
|
NA
|
HystBSO, LND
|
LCNEC, EC G2
|
Syn, CgA
|
CT (NA) + RT
|
DOD (12)
|
37
|
Pocrnich et al.
|
55
|
IVB
|
AUB, abdominal pain
|
NA
|
HystBSO, APPY, STbx
|
LCNEC, SCNEC
|
Syn, CgA, CD56
|
NA
|
DOD (3)
|
38
|
Pocrnich et al.
|
37
|
IVB
|
AUB
|
NA
|
HystBSO, Obx, Pbx
|
LCNEC, SCNEC
|
Syn, CgA
|
CT (NA)
|
DOD (2)
|
39
|
Pocrnich et al.
|
80
|
IVB
|
Dyspnea
|
NA
|
HystBSO, Pbx
|
LCNEC
|
Syn, CgA
|
None
|
DOD (3)
|
40
|
Pocrnich et al.
|
55
|
IVB
|
AUB
|
NA
|
HystBSO, LND, Obx
|
LCNEC
|
Syn
|
CT (NA)
|
DOD (9)
|
41
|
Ariura et al.
|
61
|
IB
|
AUB
|
None
|
Modified radical HystBSO, OMY, LND
|
LCNEC, EC G1
|
Syn, NSE
|
None
|
Recurrence (21), D0D (51)
|
42
|
Kobayashi A et al.
|
52
|
IIIC2
|
Abdominal pain, rapid uterine enlargement
|
Poorly differentiated carcinoma or carcinosarcoma
|
HystBSO, LND
|
LCNEC
|
Syn, CgA, CD56
|
CCRT (IP)
|
Recurrence (4), DOD (10)
|
43
|
Kobayashi M et al.
|
44
|
IIIC1
|
AGC, psychosis
|
None
|
Tumor cytoreduction
|
LCNEC, EC
|
Syn, CgA, CD56
|
Comprehensive immunomodulatory therapy, CT (TC)
|
DOD (3)
|
44
|
Yi-An et al.
|
51
|
IVB
|
AUB, pelvic mass
|
MMMT
|
HystBSO, OMY, tumor cytoreduction
|
LCNEC with superficial focal MMMT
|
Syn, CgA, CD56
|
CT (EPcis)
|
DOD (9)
|
45
|
Ogura et al.
|
52
|
IIIC2
|
AUB
|
LCNEC
|
None
|
LCNEC
|
Syn, CD56
|
Palliative care
|
DOD (1)
|
46
|
Guimarães et al.
|
75
|
IIIA
|
AUB, abdominal pain
|
Epithelioid malignant neoplasm
|
Extended total HystBSO
|
LCNEC with melanocytic differentiation
|
Syn, CgA, CD56
|
CT (CP) + RT
|
AWD (8)
|
47
|
Suh et al.
|
61
|
IIIB
|
Abdominal pain, uterine mass
|
Failed biopsy
|
HystBSO, OMY
|
LCNEC
|
Syn, CD56
|
CT (EPcis) + RT
|
Recurrence (12), DOD (23)
|
48
|
Hu et al.
|
54
|
IIIC2
|
AUB
|
Malignant tumor
|
Radical HystBSO, LND
|
LCNEC, SC
|
Syn, CgA, CD56
|
Sandwich chemoradiotherapy (EPcis)
|
NA
|
49
|
Jenny et al.
|
56
|
IVB
|
AUB, pelvic pain
|
No endometrial tissue
|
HystBSO
|
Uterine LCNEC, ovarian endometrioid adenocarcinoma G1
|
Syn
|
Planned EPcis
|
DOD (2)
|
50
|
Sekine et al.
|
56
|
IV
|
Metrorrhagia
|
None
|
None
|
LCNEC, EC
|
CgA
|
Palliative care
|
DOD (1)
|
51
|
Lee et al.
|
62
|
NA
|
AUB
|
Low-grade EC
|
NA
|
LCNEC, low-grade EC
|
Syn, CD56
|
None
|
DOD (1)
|
52
|
Akgor et al.
|
70
|
IVB
|
AUB
|
NA
|
HystBSO, LND, Obx
|
LCNEC
|
Syn, CgA, CD56
|
None
|
DOD (2)
|
53
|
Hardy et al.
|
47
|
IVB
|
Abdominal pain, distension, anorexia, loss of weight
|
LCNEC
|
Modified supralevator posterior exenteration, partial posterior vaginectomy, OMY, Hartmanns procedure
|
LCNEC, high-grade SC
|
Syn, CgA
|
CT (TP)
|
Recurrence (9)
|
54
|
Rivera et al.
|
48
|
IIIA
|
Abdominal pain, girth
|
Severe acute and chronic endometritis and pyometra
|
HystBSO, tumor cytoreduction
|
LCNEC, low-grade endometrial stromal sarcoma
|
Syn, CgA
|
CT (EPcis)
|
Recurrence (12), DOD (13)
|
55
|
Shopov et al.
|
76
|
IIIC
|
AUB, abdominal pain
|
Insufficient sample
|
HystBSO, LND, partial OMY
|
LCNEC
|
Syn, CgA, CD56
|
CT (EPcis)
|
NED (8)
|
AGC, atypical glandular cells; APPY, appendectomy; AUB, abnormal uterine bleeding; AWD, alive with disease; CCRT, concurrent chemoradiotherapy; CP, cyclophosphamide/cisplatin; CT, chemotherapy; DOD, died of disease; EC, endometrioid carcinoma; EPcar, etoposide/carboplatin; EPcis, etoposide/cisplatin; G, grade; HystBSO, hysterectomy with bilateral salpingo-oophorectomy; IP, irinotecan/cisplatin; LND, lymph node dissection; MMMT, malignant mixed Mullerian tumor; NA, not available; NED, no evidence of disease; NSE, neuron-specific enolase; Obx, omental biopsy; OMY, omentectomy; Pbx, peritoneal biopsy; RT, radiotherapy; SC, serous carcinoma; SCNEC, small cell neuroendocrine carcinoma; STbx, soft tissue biopsy; TC, paclitaxel/carboplatin; TP, paclitaxel/cisplatin. |
Likewise, we searched PubMed using the search terms ((‘PTH’[All Fields]) OR (‘parathyroid hormone’[All Fields])) AND ((‘neuroendocrine carcinoma’[All Fields]) OR (‘neuroendocrine tumor’[All Fields])). After screening the abstract of 354 citations we initially obtained, only 7 PTH-secreting LCNEC cases were identified[31–37]. In the 7 cases summarized below (Table 2), the tumor appeared to mainly affect females, and more than half of them originated from the digestive system. In most patients, the presentation of hypercalcemia-associated clinical symptoms, such as fatigue, nausea, polyuria and polydipsia, in combination with elevated serum calcium and PTH, led to the misdiagnosis of PHPT initially. Several techniques have been used to confirm the origin of ectopic PTH, including immunohistochemistry, Sestamibi radionuclide scan and quantitative RT-PCR. Among 6 cases using IHC as the confirmation tool, 3 were insufficient, and the diagnosis was inferential[35–37]. Except for well-differentiated NETs, the prognosis of PTH-secreting NEC was extremely poor, 3 out of 5 patients died of rapid progression of disease within 6 months[31, 33, 37].
Table 2
Summary of previously reported ectopic PTH-secreting neuroendocrine tumor cases
Case
|
Author [erf]
|
Age (yr) /sex
|
Initial presentation
|
PTH and calcium
|
Initial diagnosis
|
Primary site
|
Final pathology
|
Metastasis
|
IHC staining
|
Confirmationn of PTH origination
|
Treatment
|
prognosis (month)
|
1
|
Ohira et al.
|
33/F
|
Lower abdominal pain and general fatigue
|
Elevated
|
Left adnexal mass
|
Ovarian
|
NEC with component of endometrioid adenocarcinoma
|
None
|
Syn, CgA, PTH
|
IHC
|
Surgery + CT
|
Died of disease (6)
|
2
|
Vacher-Coponat et al.
|
58/F
|
Confusional syndrome
|
Elevated
|
PHPT
|
Pancreas
|
NET
|
Liver
|
NA
|
Sestamibi radionuclide scan
|
CT
|
Live with disease (6)
|
3
|
VanHouten et al.
|
74/F
|
Nausea, fatigue, polyuria, and polydipsia
|
Elevated
|
Decompensated PHPT or ectopic PTH productive malignancy
|
Pancreas
|
Poorly differentiated NET
|
Liver and retroperitoneal lymph nodes
|
PTH,PTH-rp༌NA for NET marker
|
IHC, quantitative RT-PCR
|
Palliative care
|
Died from refractory hypercalcemia and multiorgan failure (< 1)
|
4
|
Kandil et al.
|
71/F
|
Depression and fatigue
|
Elevated
|
Recurrent PHPT
|
Right thyrothymic ligament
|
NET
|
None
|
CgA, PTH
|
IHC
|
Surgery
|
In good condition (6)
|
5
|
Doyle et al.
|
28/F
|
Nausea, fatigue, abdominal pain, and weight loss
|
Elevated
|
PHPT or MEN1
|
Pancreas
|
SCNEC
|
Liver
|
NA
|
PTH reduction after tumor regression
|
CT
|
Died from recurrent hypercalcemia (15)
|
6
|
Lu et al.
|
65/M
|
Increased foam in urine
|
Elevated
|
Ectopic parathyroid adenoma
|
Mediastinal
|
Carcinoid
|
None
|
NA
|
PTH declination after rumor excision
|
Surgical excision
|
NA
|
7
|
Kwon et al.
|
44/M
|
None
|
Elevated
|
Hepatic mass
|
Liver
|
HCC and NEC
|
Bone
|
Syn, CgA, CD56
|
None
|
Surgery + CCRT
|
Died of disease progression (2)
|
IHC: immunohistochemistry; HCC, hepatocellular carcinoma; MEN I, Multiple endocrine neoplasia type I. |