Journal of Pathology and Translational Medicine

Case Studies

Primary carcinoid tumor in the external auditory canal: Dong Hae Chung, Gyu Cheol Han, Na Rae Kim; J Pathol Transl Med. 2020;54(2):184-187. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.11.07

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A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.

Citations

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Incidental finding of a neuroendocrine neoplasm in a suspected ear canal exostosis
Alexander Wieck Fjaeldstad, Gerda Elisabeth Villadsen, Gitte Dam, Stephen Jacques Hamilton-Dutoit, Thomas Winther Frederiksen
Otolaryngology Case Reports.2022; 22: 100394. CrossRef
68Ga-DOTATATE Uptake in Well-Differentiated Neuroendocrine Tumor of the External Auditory Canal
Özge Erol Fenercioğlu, Ediz Beyhan, Rahime Şahin, Mehmet Can Baloğlu, Tevfik Fikret Çermik
Clinical Nuclear Medicine.2022; 47(8): e552. CrossRef

Combined Hepatocellular Carcinoma and Neuroendocrine Carcinoma with Ectopic Secretion of Parathyroid Hormone: A Case Report and Review of the Literature: Hyun Jung Kwon, Ji-Won Kim, Haeryoung Kim, YoungRok Choi, Soomin Ahn; J Pathol Transl Med. 2018;52(4):232-237. Published online May 25, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.17

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Abstract PDF

Primary combined hepatocellular carcinoma (HCC) and neuroendocrine carcinoma is a rare entity, and so is hypercalcemia due to ectopic parathyroid hormone (PTH) secretion by tumor. A 44-year old man with hepatitis B virus associated chronic liver disease presented with a hepatic mass. Hemihepatectomy discovered the mass as combined HCC and poorly differentiated cholangiocarcinoma. During adjuvant chemoradiation therapy, he presented with nausea, and multiple systemic metastases were found. Laboratory tests revealed hypercalcemia with markedly elevated PTH and neuron specific enolase. Parathyroid scan showed normal uptake in parathyroid glands, suggestive of ectopic PTH secretion. Subsequently, immunohistochemistry of neuroendocrine marker was performed on the primary lesion, and confirmed the neuroendocrine differentiation in non-HCC component. The patient died 71 days after surgery. This report may suggest the possibility of ectopic PTH secretion by neuroendocrine carcinoma of hepatic origin causing hypercalcemia. Caution for neuroendocrine differentiation should be exercised when diagnosing poorly differentiated HCC.

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Parathyroid Carcinoma and Ectopic Secretion of Parathyroid hormone
Filomena Cetani, Elena Pardi, Claudio Marcocci
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Primary hepatic neuroendocrine cancer coexisted with hepatocellular carcinoma: a case report
Chikara Ebisutani, Seitetsu Yoon, Toshiki Hyodo, Takafumi Watanabe, Hirofumi Okada, Yutaka Shirakawa, Yoshio Sakamoto, Shigeya Hirohata
Kanzo.2020; 61(3): 122. CrossRef
Two-in-one: A pooled analysis of primary hepatic neuroendocrine carcinoma combined/collided with hepatocellular carcinoma
Jia-Xi Mao, Fei Teng, Ke-Yan Sun, Cong Liu, Guo-Shan Ding, Wen-Yuan Guo
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Primary hepatic neuroendocrine carcinoma coexisting with distal cholangiocarcinoma
Qi Xin, Rong Lv, Cheng Lou, Zhe Ma, Gui-Qiu Liu, Qin Zhang, Hai-Bo Yu, Chuan-Shan Zhang
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Review

Neuroendocrine Tumors of the Female Reproductive Tract: A Literature Review: Yi Kyeong Chun; J Pathol Transl Med. 2015;49(6):450-461. Published online October 13, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.20

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Abstract PDF

Neuroendocrine tumors of the female reproductive tract are a heterogeneous group of neoplasms that display various histologic findings and biologic behaviors. In this review, the classification and clinicopathologic characteristics of neuroendocrine tumors of the female reproductive tract are described. Differential diagnoses are discussed, especially for non-neuroendocrine tumors showing high-grade nuclei with neuroendocrine differentiation. This review also discusses recent advances in our pathogenetic understanding of these disorders.

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Original Articles

Morphologic Analysis of Pulmonary Neuroendocrine Tumors: Seung Seok Lee, Myunghee Kang, Seung Yeon Ha, Jungsuk An, Mee Sook Roh, Chang Won Ha, Jungho Han; Korean J Pathol. 2013;47(1):16-20. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.16

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Abstract PDF

Background

Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis.

Methods

Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measured the nuclear area, perimeter, and the major and minor axes.

Results

The mean nuclear area was 0.318±0.101 µm² in typical carcinoid tumors, 0.326±0.119 µm² in atypical carcinoid tumors, 0.314±0.107 µm² in small cell carcinomas, and 0.446±0.145 µm² in large cell neuroendocrine carcinomas. The mean nuclear circumference was 2.268±0.600 µm in typical carcinoid tumors, 2.408±0.680 µm in atypical carcinoid tumors, 2.158±0.438 µm in small cell carcinomas, and 3.247±1.276 µm in large cell neuroendocrine carcinomas. All parameters were useful in distinguishing large cell neuroendocrine carcinoma from other tumors (p=0.001) and in particular, nuclear circumference was the most effective (p=0.001).

Conclusions

Pulmonary neuroendocrine tumors showed nuclear morphology differences by subtype. Therefore, evaluation of quantitative nuclear parameters improves the accuracy and reliability of diagnosis.

Citations

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Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
Young Bae Choi, Go Eun Bae, Na Hee Lee, Jung-Sun Kim, Soo Hyun Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo
Journal of Korean Medical Science.2015; 30(8): 1062. CrossRef
Morphologic Alteration of Metastatic Neuroblastic Tumor in Bone Marrow after Chemotherapy
Go Eun Bae, Yeon-Lim Suh, Ki Woong Sung, Jung-Sun Kim
Korean Journal of Pathology.2013; 47(5): 433. CrossRef

Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors: Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han; Korean J Pathol. 2012;46(3):221-225. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221

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Abstract PDF

Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

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Paul D. Barone, Chen Zhang
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Clinical Significance of Persistent Tumor in Bone Marrow during Treatment of High-risk Neuroblastoma
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Case Reports

Mixed Endocrine-Exocrine Carcinoma of Gallbladder Derived from Dysplasia.: Min Jin Lhee, Ji Young Woo; Korean J Pathol. 2011;45(5):537-541.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.537

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Abstract PDF: A rare case of multiple mixed endocrine-exocrine carcinoma (MEEC) of gallbladder in a 68-year-old man is described. The lesions were two separate nodules (17x13x7 mm and 17 mm in length) on the mucosa, which were composed of predominant neuroendocrine carcinoma (NEC) infiltrating into the adventitia and minor portion of adenocarcinoma (AC) or high grade dysplasia (HGD) on the surface. Surrounding mucosa showed areas of low grade dysplasia (LGD). Two nodal metastases out of 16 nodes were found containing NEC component. By immunohistochemistry, human mutL homolog 1 (hMLH1), p53, human mutS homolog 2 (hMSH2) and human mutS homolog 6 (hMSH6) showed diffuse strong positive reaction in HGD, AC and NEC, contrasting with weak positive reaction in LGD. On genetic analysis, all lesions of HGD, AC, and NEC except for LGD showed positive loss of heterozygosity in D5S346 locus. For microsatellite instability and K-ras mutation tests, all lesions showed negative results. Common immunophenotypes and molecular results among HGD, AC, and NEC suggested that NEC of this MEEC was derived from the dysplasia-AC sequence.

A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma Co-existing with Mucinous Carcinoma: A Case Report.: Sunhee Chang, Sang Hwa Shim, Mee Joo, Hanseong Kim, Yong Kyu Kim; Korean J Pathol. 2010;44(1):97-100.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.97

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An endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare skin tumor that most commonly occurs on the eyelids of elderly women. This tumor is morphologically analogous to endocrine ductal carcinoma in situ and solid papillary carcinoma of the breast. We describe one case of a 51-year-old male with an EMPSGC co-existing with mucinous carcinoma of the eyelid. The tumor was composed of dilated ducts with a smooth border and was partially filled with a papillary proliferation. Tumor cells were uniform, small-to-medium in size, and oval-to-polygonal with light eosinophilic cytoplasm. Nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Tumor cells expressed chromogranin, synaptophysin, estrogen and progesterone receptors, cytokeratin 7, and epithelial membrane antigen.

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A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid
Ji Eon Kang, Sung Eun Kim, Suk-Woo Yang
Journal of the Korean Ophthalmological Society.2023; 64(2): 149. CrossRef
Endocrine mucin-producing sweat gland carcinoma: a systematic review and meta-analysis
Michael H. Froehlich, Keith R. Conti, Ivy I. Norris, Jordan J. Allensworth, Nicole A. Ufkes, Shaun A. Nguyen, Evelyn T. Bruner, Joel Cook, Terry A. Day
Journal of Dermatological Treatment.2022; 33(4): 2182. CrossRef
Next-generation sequencing analysis suggests varied multistep mutational pathogenesis for endocrine mucin-producing sweat gland carcinoma with comments on INSM1 and MUC2 suggesting a conjunctival origin
Joseph G. Mathew, Anita S. Bowman, Jad Saab, Klaus J. Busam, Kishwer Nehal, Melissa Pulitzer
Journal of the American Academy of Dermatology.2022; 86(5): 1072. CrossRef
Endocrine mucin‐producing sweat gland carcinoma and associated primary cutaneous mucinous carcinoma: Review of the literature
Rebecca Tian Mei Au, Manish M. Bundele
Journal of Cutaneous Pathology.2021; 48(9): 1156. CrossRef
An Update on Endocrine Mucin-producing Sweat Gland Carcinoma
Meghana Agni, Meisha L. Raven, Randy C. Bowen, Nora V. Laver, Patricia Chevez-Barrios, Tatyana Milman, Charles G. Eberhart, Steven Couch, Daniel D. Bennett, Daniel M. Albert, R. Nick Hogan, Paul O. Phelps, Hillary Stiefel, Norberto Mancera, Martin Hyrcza,
American Journal of Surgical Pathology.2020; 44(8): 1005. CrossRef
A Case of Endocrine Mucin-Producing Sweat Gland Carcinoma: Is it Still an Under-Recognized Entity?
Khaled A. Murshed, Mohamed Ben-Gashir
Case Reports in Dermatology.2020; 12(3): 255. CrossRef
Endocrine Mucin-Producing Sweat Gland Carcinoma, a Histological Challenge
Mary Anne Brett, Samih Salama, Gabriella Gohla, Salem Alowami
Case Reports in Pathology.2017; 2017: 1. CrossRef
Endocrine mucin‐producing sweat gland carcinoma occurring on extra‐facial site: a case report
Jia‐Huei Tsai, Tzu‐Lin Hsiao, Yi‐Ying Chen, Cheng‐Hsiang Hsiao, Jau‐Yu Liau
Journal of Cutaneous Pathology.2014; 41(6): 544. CrossRef
Endocrine Mucin-Producing Sweat Gland Carcinoma
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The American Journal of Dermatopathology.2013; 35(1): 117. CrossRef

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report.: Yun Kyung Kang, Jae Whoan Koh; Korean J Pathol. 2008;42(6):389-392.

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Abstract PDF: Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

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