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Cephalic undifferentiated carcinoma with osteoclast-like giant cells arising from the main pancreatic duct: case report and literature review.


Undifferentiated carcinoma with osteoclast-like giant cell is a rare entity, firstly described in 1968 by Rosai [1]. This pathologic entity is reported in the mainstream under various terms: metaplastic/anaplastic carcinoma, osteoclastoma, or osteoclastic giant cell tumor [2-5].

The key element for diagnosis consists in the association of tumoral mononuclear cells with a variable number of non-tumoral multinucleated cells, osteoclast-like [6]. Summing less than 1% among malignant epithelial pancreatic proliferations [7], the tumor has origin in the pancreatic ductal epithelium and a similar genic signature with ductal carcinoma [8], but very different morphology and variable prognosis [9, 10]. Even if data about UCOGC are accumulating, there are still unexplained events in the tumor biology. Recent research addresses the role of osteoclast-like giant cells [5, 11], the involvement of different pancreatic intraductal lesions, presumed as origin point [3, 12-14], and the identification of the morphological alterations sequence leading from ductal epithelium to UCOGC [15].

Therefore, we present a case of UCOGC associated with conventional ductal carcinoma, arising from the main pancreatic duct epithelium. By highlighting the main clinicopathological features, our report complements data already published on this topic and contributes to a better characterization of the tumor behavior.

Case report

We describe the case of a 76-year-old female presented at the Surgical Department of "Sf. Spiridon" County Emergency Hospital with a large palpable upper abdominal tumor. The patient reported right upper abdominal pain, nausea, vomiting, asthenia and weight loss during the last month. She also had a history of ischemic heart disease and chronic cardiac failure NYHA II. Physical examination revealed pale, not jaundiced, dehydrated skin, cachexia (BMI=16.5 kg/m), and a 12/10 cm mass located in epigastrium and right hypochondrium, mobile, firm and well-circumscribed. Laboratory tests revealed moderate anemia (Hb=9.9 g/dL, Ht=31%), high levels of carbohydrate antigen 19-9 (C[A.sub.19-9] =194 U/mL; normal <33 U/mL) and C reactive protein (CRP=3.59 mg/L; normal <0.5 mg/L). Abdominal computed tomography (Figure 1) revealed a heterogeneous tumor of 83/130/100 mm, predominantly cystic, belonging to the head of the pancreas, in close contact with the superior mesenteric vein and spleno-mesenteric vein (on a length of over 55 mm), narrowing the vessels without thrombosis; Wirsung duct was dilated (10 mm in diameter); peritumoral lymphadenopathies were noted. Due to the close contact of the tumor with the vascular components, and the patient's anaesthetic risk (ASA IN), an exploratory laparotomy was first performed. This procedure showed a cephalic pancreatic tumor invasive into the antro-pyloric region of the stomach, without liver involvement; the lymph nodes were negative for tumoral cells on frozen section. The surgical team decided to continue the surgery with the Whipple procedure, removing the entire expansive process (Figure 2).

Gross examination of the surgical specimen revealed a 115/70 mm pancreatic mass, firm, relatively well-circumscribed, located in the cephalic zone with intraluminal extension into the dilated main pancreatic duct towards ampullary region; thus, the major duodenal papilla was still permeable. On cut section, the tumor appeared heterogeneous, with solid tan areas, low density brown-reddish areas and microcystic lesions.

Tissue samples were fixed in 10% formalin, embedded in paraffin blocks, sectioned at 4-[micro]m thickness, and stained with Hematoxylin-eosin for light microscopy evaluation.

The pancreatic tissue samples presented a diffuse tumor proliferation composed mainly of large mononuclear pleomorphic cells, from round-ovoid to spindle-shaped, discohesive, with inconspicuous mitotic activity (1-2 mitosis/HPF), associated with numerous, diffusely spread multinucleated osteoclast-like giant cells, phagocitically active, and moderate desmoplastic stroma. The tumor growth patterns were pushing border, endoluminal/polypoid and infiltrative into the stroma (Figures 3-5). Areas of tumor necrosis and hemorrhage were also identified.

Areas of tumor necrosis and hemorrhage were also identified. The tumor proliferation originated into the main pancreatic duct and extended focally into the duodenal wall without muscular layer or gastric antrum involvement. The main pancreatic duct was dilated, focally with high grade dysplasia, associating foci of invasive ductal adenocarcinoma (Figure 6).

The adjacent pancreatic parenchyma presented pancreatic intraepithelial neoplasia (PanIN low-grade and high-grade) and chronic pancreatitis foci (Figure 7).

The surgical resection margins and 16 lymph nodes were negative for tumor cells.

The histological aspects oriented towards an UCOGC associated with conventional pancreatic ductal carcinoma.

Further immunohistochemistry examination using monoclonal antibodies against cytokeratin (Dako, clone AE1/AE3, dilution 1:50), CD68 (Novocastra, clone 514H12, dilution 1:100) and Vimentin (Novocastra, clone V8, dilution 1:150) confirmed the diagnosis of UCOGC.

The multinucleated osteoclastic giant cells were strongly positive for CD68 and Vimentin, and negative for CK AE1/AE3, and the pleomorphic tumoral cells were positive for CK AE1/AE3 and Vimentin (Figures 8-10).

Due to favorable uneventful post-operatory evolution the patient was discharged on 9th day with the diagnosis of stage IIA UCOGC (pT3N0M0 LV0Pn0), associated with invasive conventional pancreatic ductal carcinoma (5%). Unfortunately, the patient died 4 months after surgery, without any documented recurrent or metastatic neoplastic process.


WHO 2010 sets undifferentiated carcinoma with osteoclast-like giant cell and pleomorphic giant cell as a pancreatic ductal adenocarcinoma variant, although UCOGC is a tumor with a much better prognosis [16].

The awareness regarding UCOGC led to an increase of the number of published papers: from less than 50 cases between 1968-2011 [11] to over 150 nowadays, including several studies performed on larger groups that also associate ultrastructural, molecular and genetic data.

However, the lack of consensus concerning the histopathological assessment, clinical course or surgical management is due to the relative rarity of this type of tumor [8, 9]. One of the main issues regards the origin the precise lineage of tumor components being a matter of debate. Three different hypotheses were formulated, sustaining either an epithelial origin, a mesenchymal origin or a common pluripotent progenitor which undergoes both epithelial and mesenchymal dedifferentiation [6, 17, 18]. Nowadays, the epithelial origin is the most widely accepted, based on the K-ras codon 12 mutation identified in the mononuclear tumor cells--that is one of the driver mutation also present in conventional pancreatic duct adenocarcinoma, and on the retained expression of epithelial markers (CK, EMA)--at least focally [19]. On the other hand, the vimentin expression in the mononuclear cells of this epithelial tumor sustains the epithelial-mesenchymal transition within the carcinogenic process [20]. However, the positive mesenchymal and epithelial markers could support the interconnection of these three theories.

Despite all this evidence, it is still unknown how the same genetic driver mutations and the same preneoplastic lesions as ductal carcinoma can lead to such different histological features. Most probably, the UCOGC pathogenic mechanism involves not only somatic mutations, but also other molecular events [8].

The common clinical presentation of UCOGC is nonspecific and includes symptoms such as upper abdominal pain, jaundice, anorexia, steatorrhea, weight loss, anemia, elevated CA 19-9, CEA and CRP levels [21, 22]. Unusual presentation includes diabetes exacerbation, melena, impaired liver function or fatigue.

Gross evaluation usually reveals a cystic tumor with solid component, with large areas of necrosis commonly confined to the head of the pancreas. This situation can be associated with dilated main pancreatic duct, especially if the polypoid endoluminal growth pattern is present. It appears that 60% of the cases have intracystic/ductal prominent growth. The described nodular pushing border could represent ducts filled in by the tumoral process [9, 11, 13].

Although the tumor grows rapidly--more than half of reported cases measuring over 10 cm at the time of the diagnosis, incidental small sized tumors or "in situ" lesion are documented [10, 15, 23, 24].

The gold standard in diagnosis consists in the identification of the two cell populations, the pathognomonic element being the benign-looking multinucleated giant cells associated with mononuclear pleomorphic tumor cells. The appearance of osteoclast-like giant cells, beside tumor mononuclear histiocyte-like cells, is considered as an early event in tumor progression [15]. The different pancreatic neoplastic components/patterns should be assessed as percentages [25]. Recent data underline the value of a preoperative diagnosis by using fine needle aspiration, that could be decisive in adequate therapy and prognostic stratification [10, 21,26].

Differential diagnosis should always include all the pancreatic cystic lesions: mucinous cystic neoplasm, intraductal papillary mucinous neoplasm (IPMN), neuroendocrine tumors, pancreatic ductal adenocarcinoma, pseudocyst, due to the most frequently gross appearance of a mixed cystic-solid lesions. It should also include ductal carcinoma with micropapillary features, "groove" pancreatitis due to cells resembling osteoclast-like giant cells or gastrointestinal stromal tumors [9, 10, 12, 27].

Classically, UCOGC was considered a tumor with dismal prognosis, but recently published case series reporting long-term survivors has shown the opposite [2, 10, 28, 29]. Consequently, UCOGC can be considered a "good" type of pancreatic cancer compared to conventional pancreatic ductal adenocarcinoma, with a 5-years survival of around 60%. The variability of survival results available in the mainstream, from 4 months to 7 years, could be explained by individual tumor biology, uneven pathological evaluation of such large tumors, differences in surgical protocol, histological heterogeneity of the tumor (see grading), or different protocols of chemotherapy or radiotherapy [9, 30].

The pure forms of UCOGC, even in locally advanced stages, have a better prognosis than the cases associated with ductal adenocarcinoma [10]. The recurrent tumor process in residual pancreatic tissue or the development of metastases were most frequently composed of conventional pancreatobiliary carcinoma [2, 28], followed by the spindle-shaped component [30], with or without osteoclast-like giant cells. Our case had undifferentiated carcinoma predominance, which represented around 95% of the tumor. Foci of ductal carcinoma (5%) were identified on careful examination. The importance of thorough extensive examination is relevant because of the likelihood of metastases or recurrences of the ductal component, regardless its dominant or focal appearance [2, 9, 26, 28].

The only treatment with curative intention remains the surgical resection [10, 22], similar to classic pancreatic cancer: duodeno pancreatectomy for cephalic localization and splenopancreatectomy for body/tail localization [13]. The use of radio- or chemotherapy has been reported in sporadic cases using gemcitabine, 5-fluorouracil, paclitaxel but the small number of patients who received adjuvant therapy can not lead to safe conclusions [29-32].

The particularity of our case consists in capturing the morphological alteration sequence on a large cephalic UCOGC arising from the main pancreatic duct. This evidence complements previously reported data regarding the evident ductal involvement in UCOGC, but on smaller size tumors [15, 24, 33]. In our case, extensive sampling allowed us to identify various epithelial changes of the pancreatic ductal system. The main pancreatic duct was dilated and presented high grade dysplasia, but in the absence of a clear epithelial papillary proliferation we ruled out an IPMN. The increased dimensions of the main pancreatic duct could be explained by inflammation or partially obstructive endoluminal tumor. At some point, the epithelium of the main pancreatic duct clearly displayed cytological atypia and became stratified with a sudden shift to pleomorphic mononuclear round and spindle cells chaperoned by benign looking osteoclast giant cells. The focal atypical epithelial hyperplasia could be the result of both intraductal neoplasia and squamous metaplasia [33, 34], difficult to differentiate sometimes on H&E staining. Immunohistochemistry examination using CK 5/6 and Ki-67 has been pointed as useful [34], but unfortunately was not performed on our case. To the best of our knowledge, there are only three other cases of cephalic UCOGC reported surprising the similar sequence of histopathological changes [15, 24, 33].

We also noted, in the nearby smaller branches of main pancreatic duct, the presence of intraepithelial neoplasia, low- and high-grade. Ductal intraepithelial neoplasia was described in a large number of cases, in some of them in direct connection with the UCOGC [24, 35]. The most frequent preneoplastic lesion associated with UCOGC is mucinous cystic neoplasm (MCN), followed by IPMN and PanIN, with at least some foci of high-grade dysplasia [9, 12]. Beside the classic pattern described, we also identified small cystic structures in the pancreatic parenchyma with a rim of UCOGC, which could be the result of intraductal neoplasia spread replacing ductal epithelium, similar to "cancerization of ducts" described in classic ductal carcinoma [36]. Osteoid change, vascular emboli, perineural invasion, and/or lymph node metastasis--histological features frequently present in the ductal pancreatic adenocarcinoma [9], were not found in our case.

The different scoring systems lead to difficulty in establishing the prognosis. Our case was assessed as low grade tumor grade I, with abundant large osteoclast giant cells and background cells with minimal atypia and scant mitoses, in accordance with the histopathological grading based on the scoring system of Netherlands Committee on Bone Tumors [9], but also as grade 3--poorly differentiated tumor by using the exocrine pancreatic carcinoma grading from WHO 2010 [16] and as grade 4 according to The American Joint Committee on Cancer staging manual 8th edition [37]. These inadvertences require further studies to decide the usefulness of one score versus another.

The main clinical and pathology features of UCOGC present in the mainstream are summarized in Table 1 and Table 2. The PubMed search was performed by using the key-words "anaplastic" and "pancreas" alongside "osteoclast-like giant cell" and "pancreas", due to the multiple synonyms for UCOGC. From a total of 321 articles, we eliminated all papers without English text available or describing tumors without osteoclast-like giant cells, and we obtained 61 items. These papers include 30 case reports with tail location, 17 case reports with cephalic location and 14 case series. Therefore, the rarity of this pathological entity, mainly at cephalic site, sustains the value of our paper.

The cephalic location overlaps with the general features of UCOGC described earlier, although we can identify a tendency to smaller lesions (10 cases under 5 cm). Early intraductal neoplasia with dysplastic epithelium and abrupt change of tumor phenotype was rarely registered. The intraductal growth included polypoid masses in the main pancreatic duct and branches or extruding through ampulla.

The review of the literature shows a significant number of cases (9 of 17) associated with ductal neoplasia, intraductal or invasive. From a "ductal variant" point of view, the split carcinogenic process of ductal carcinoma with PanIN origin in acinar cells and IPMN origin in ductal cells could also reflect in UCOGC carcinogenesis, explaining the heterogeneity and variability of tumor behavior. Moreover, the intraductal growth pattern which significantly overlaps with IPMN-morphology could imply the IPMN ductal/UCOGC tumoral transformation axis, although there are cases of IPMN coexisting with ductal carcinoma molecularly unrelated [38, 39]. The PanIN--ductal carcinoma sequence, presumed until recently as originating from ductal epithelium, has been recently stated as acinar--derived with achieved ductal features through acinar ductal metaplasia [38], which can also be caused by inflammation [40]. A number of two cases associated documented pancreatitis prior to UCOGC diagnosis and one had highgrade PanIN. Muraki et al. also reported one patient with intraductal growth and personal history of pancreatic acute inflammation. On surgical resected specimen is difficult to evaluate pancreatitits without clinical evidence, mainly because of the peritumoral pancreatitis associated with large size.

The divergent survival data result from the combination, in the case series, of the pleomorphic giant cell type and osteoclast-like giant cell type, each of them with different clinical behavior and survival [16].


UCOGC is a rare ductal carcinoma variant with great heterogeneity which provide nonspecific symptoms and in shaping morphological landscape, with histogenesis still under debate. Our case report confirms the ductal epithelial origin, pointing out the similar carcinogenic process with ductal carcinoma (through PanIN) and an abrupt shift to undifferentiated carcinoma phenotype. The molecular changes which determine the sudden transition remain to be discovered, further studies being necessary.


Written informed consent was obtained from the patient for publication of this case report.

Competing interests

The authors declare that they have no competing interests.


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Andreea Rusu (1), Simona Eliza Giusca (2), Delia Gabriela Ciobanu Apostol (2,3), Lidia Ionescu *, (4), Irina-Draga Caruntu (1)

(1) Department of Morphofunctional Sciences I--Histology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania; Department of Morphofunctional Sciences I--Pathology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania; Department of Pathology "Sf. Spiridon" County Clinical Emergency Hospital, Iasi, Romania; 4Department of Surgery, Third Surgery Clinic, "St. Spiridon" County Clinical Emergency Hospital, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania

Received: February 2019; Accepted after review: March 2019; Published: March 2019.

Corresponding author: Lidia Ionescu, MD, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Str, Iasi, Romania.


DOI: 10.22551/2019.22.0601.10148

Caption: Fig. 1. Cephalic pancreatic tumour predominantly cystic in tight contact with the superior mesenteric vein.

Caption: Fig. 2. Surgical specimen: antrum, duodenum, first jejunal loop, head of the pancreas presenting tumor mass and distal commone bile duct.

Caption: Fig. 3. UCOCG--solid area with 'pushing border' margin composed of pleomorphic mononuclear cells, ovoid or spindlle, and numerous diffusely spread large cells with eosinophilic cytoplasm and 5-20 centrally located blunt nuclei (HE, x100).

Caption: Fig. 4. Dilated pancreatic duct mostly covered with columnar epithelium and endoluminal tumor growth (HE, scanned specimen). Large insert--stratified ductal epithelium with citological atypia (at the polipoid tumor stalk) with a sudden morphology switch to UCOGC (pleomorhic mononuclear cells with abundant large multinucleated cells). Small insert--"Incomplete" duct asociated with micropapillary features mimicking giant cells (highly sugestive for invasive ductal carcinoma).

Caption: Fig. 5. Invasive front of UCOGC with desmoplastic stroma, small recent hemorrhagic area and entraped adipocites (HE, x100).

Caption: Fig. 6a. Main pancreatic duct with dysplastic epithelium and isolated duct-like structures with pleomorphic nuclei and mild desmoplastic response (ductal carcinoma foci) (HE, x100).

Caption: Fig. 6b. Main pancreatic duct towards apullary zone with high grade dysplasia (HE, x100).

Caption: Fig. 7a. High grade PanIN versus immature squamos metaplasia (HE, scanned specimen).

Caption: Fig. 7b. Small main pancreatic duct branches with low and high grade intraepithelial neoplasia (HE, x100).

Caption: Fig. 8. CD 68 positive mononuclear inflamatory cells (hystiocyte) and large round benign-looking cells with centrally numerous nuclei (osteoclast-like giant cells) (IHC, anti-CD68, x100).

Caption: Fig. 9. CK AE1/AE3 positive on round-ovoid and spindlle mononuclear proliferation alongside negative multinucleated large cells with 5-15 nuclei centrally located (IHC, anti-CK AE1/AE3, x200).

Caption: Fig. 10. Vimentin marking both mononuclear tumoral cells and non-tumoral multinucleated osteoclast-like gians cells (IHC, anti-vimentin, x100).
Table 1. Cephalic UCOGC, single case reports

Author                 Age   Tumor          Clinic
                       Sex   size           presentation

1. Mullick et al.,     83    10 cm          Weight loss, low
1996 [41]              F                    hemoglobin, normal CA

2. Carvounis et al.,   70    7 cm           Obstructive unpainful
2003 [42]              F                    jaundice, normal CA 19-9

3. Loya et al.,        50    7 cm           Jaundice, abdominal pain
2004 [43]              M                    elevated CA 19-9

4. Nai et al.,         69    4.7 cm         Weight loss
2005 [44]              M

5. Tezuka et al.,      68    4.2 cm         Abdominal pain
2006 [24]              F

6. Bergmann et al.,    45    0.8 cm         Abdominal pain, fatty
2007 [15]              F                    stools, elevated CRP,
                                            normal CA 19-9

7. Koorstra et al.,    39    3 cm           NM
2008 [45]              M

8. Manduch et al.,     66    9.5 cm         Wight loss, painless
2009 [46]              M                    jaundice, melena stool

9. Mannan et al.,      40    4 cm           Progressive jaundice,
2010 [47]              F                    elevated serum bilirubin

10. Maksimov et al.,   68    2.5 cm         Painless jaundice,
2011 [33]              F     pedunculated   elevate bilirubin
                             mass           and transaminases
                             3 cm cystic

11. Kobayashi et       39    4 cm           Epigastralgia, elevated
al., 2014 [28]         F                    levels of serum amylase
                                            and CA 19-9

12. Fujii et al.,      68    1.9 cm         Fatigue
2016 [3]               F                    Impaired liver function

13. Georgiou et al.,   75    9 cm           Abdominal pain, fatty
2016 [5]               F                    stools, weight loss,
                                            elevate CA 19-9

14. Fujimoto et al.,   70   Initially       Diabetes
2018 [23]                   2.2 cm          exacerbation
                       F    After 11
                            months 18 cm

15. Guo et al.,        65   5.8 cm          Weight loss
2018 [13]              M

16. Oka et al.,        72   2.5 cm          Elevated serum
2018 [48]              F                    amylase and CA

17. Yepuri et al.,     78   2.1 cm          Fatigue, weight
2018 [49]              M                    loss, abdominal

Author                Gross aspects   Preneoplastic   Other invasive
                                      pancreatic      carcinoma
                                      lesions         Associated

1. Mullick et al.,     Solid           NM             UCPGC
1996 [41]

2. Carvounis et al.,   Cystic-solid    NM             No
2003 [42]              dilated CBD

3. Loya et al.,        Solid-cystic    NM             DC
2004 [43]                                             UCPGC

4. Nai et al.,         Solid           NM             Mucus secreting
2005 [44]              Dilated MPD                    conventional
                                                      including single

5. Tezuka et al.,      Polypoid        NM             Focal peripheral
2006 [24]              intraductal                    glandular
                       tumor                          pattern
                       Dilated MPD

6. Bergmann et al.,    Cystic          HG and LG       No
2007 [15]              Dilated MPD     PanIN

7. Koorstra et al.,    Partial         HG and LG       No
2008 [45]              cystic          PanIN

8. Manduch et al.,     Ulcerated       NM              No
2009 [46]              ampulla with
                       solid tumor
                       Dilated CBD

9. Mannan et al.,      NM              NM              UCPGC
2010 [47]

10. Maksimov et al.,   Dilated MPD     HG and LG      Intratumoral
2011 [33]              and CBD         PanIN          conventional DC
                       Cystic                         (polypoid mass)
                       process and

11. Kobayashi et       Cystic-solid    NM             Conventional DC
al., 2014 [28]         MPD with

12. Fujii et al.,      Cystic-solid    Main and        No
2016 [3]               Dilated MPD     brunch duct
                       and CBD         HG IPMN

13. Georgiou et al.,   Cystic-solid    NM              DC
2016 [5]               MPD dilated,
                       normal CBD

14. Fujimoto et al.,   NM              NM              NM
2018 [23]

15. Guo et al., 2018   Cystic-solid    NM              NM
[13]                   Dilated MPD

16. Oka et al., 2018   Cystic, not     NM              NM
[48]                   connected to
                       dilated MPD

17. Yepuri et al.,     Solid mass      NM              UCPGC
2018 [49]

Author                 Relapse/        Adjuvant         Other
                       Survival        therapy          mentions

1. Mullick et al.,     NM              NM               History of
1996 [41]                                               breast
                                                        And lobular
                                                        (6 years ago)

2. Carvounis et al.,   Relapse 9       No               Negative
2003 [42]              months                           lymphnodes

3. Loya et al.,        NM              Gemcitabine
2004 [43]

4. Nai et al.,        Relapse 6        NM               Positive
2005 [44]             moths                             lymphnode for
                      (multiple                         UCOGC Osteoid
                      Survival 1

5. Tezuka et al.,     No relapse       NM               Non invasion
2006 [24]             (surveillance                     tumor
                      22 months)

6. Bergmann et al.,   NM               NM               Diabetes
2007 [15]                                               mellitus type
                                                        2 History of
                                                        carcinoma (1

7. Koorstra et al.,   NM               NM              History of
2008 [45]                                              alcoholic
                                                       Leiden mutation
                                                      (FAMMM syndrome)

8. Manduch et al.,    Relapse 6        No              Osteochondroid
2009 [46]             months                           differentiation
                      (lymphnode                       (1 cm)
                      and liver
                      Survival 1

9. Mannan et al.,     NM               NM
2010 [47]

10. Maksimov et       No relapse       NM              Personal
al., 2011 [33]        (surveillance                    history of
                      36 months)                       type 2

11. Kobayashi        After 4 years     Gemcitabine
et al., 2014 [28]    intra-            after first
                     pancreatic        surgery
                     metastases with
                     DC component
                     than 5 years

12. Fujii et al.,    No                S-1            UCOGC with
2016 [3]             (surveillance                    origin in IPMN
                     period 18                        epithelium

13. Georgiou et      Died after 10     No             Personal
al., 2016 [5]        months                           history of
                     Local                            acute idiopathic
                     recurrence                       pancreatitis (3
                     after 6 months                   years before)
                                                      CHA invaded

14. Fujimoto et      Died after 12    Oral            Original
al., 2018 [23]       months           adminis-        diagnosis made
                                      tration         after EUS-FNA,
                                      of TS-1         unresectable
                                      (tegafur        tumor

15. Guo et al.,      NO                NO             Personal history
2018 [13]            (surveillance                    of diabetes
                     period 10

16. Oka et al.,      NO               oral
2018 [48]            (surveillance    tegafur
                     period 6         /gimeracil/
                     months)          oteracil

17. Yepuri et al.,   NO               NM              Personal history
2018 [49]            (surveillance                    of prostatic
                     period 3                         cancer and
                     years)                           large mantle
                                                      cell lymphoma

Table 2. UCOGC, case series

Author                   Number of    Cephalic        Age/Sex
                         reported     localization

1. Alguacil-Garcia       2            1               NM
et al., 1977 [2]

2. Deckard-Janatpour     11           NM              NM
et al., 1998 [50]

3. Hoorens et al.,       2            2               57/M
1998 [51]                                             44/F

4. Molberg et al.,       9            NM              NM
1998 [52]

5. Chopra et al.,        2            2               89/M
2007 [53]                                             64/F

6. Layfield et al.,      6            1               59/M
2008 [54]

7. Naito et al.,         7            3               51/F
2009 [55]                                             76/F

8. Nojima et al.,        2            2               70/M
1993 [56]                                             72/M

10. Sakai et al.,        3            2               49/M
2000 [57]                                             51/M

11. Muraki et al.,       38           61.1%           Mean age=57.9
2016 [9]                                              22 cases F

12. Reid et al.,         14           7               4F
2017 [26]                                             3M
                                                      Mean age=63
                                                      (range from 43
                                                      to 75 years)

13. Luchini et al.,      22           NM              12 F
2017 [8]                              17 cases        10M

14. Fukukura et al.,     7           4                3M
2019 [58]                                             4F
                                                      Mean age = 71.1
                                                      (range from 59
                                                      to 82 years)

Author                   Survival             Gross aspects

1. Alguacil-Garcia       NM                   Cystic-solid
et al., 1977 [2]

2. Deckard-Janatpour     NM                   NM
et al., 1998 [50]

3. Hoorens et al.,       Male patient         Mean size =
1998 [51]                discovered tumor     6 cm

4. Molberg et al.,       8 succumbed in       Partially or
1998 [52]                under 1 year         completely
                                              Average 9 cm

5. Chopra et al.,        NM                   2 cm
2007 [53]                                     3.1 cm

6. Layfield et al.,      NM                   NM
2008 [54]

7. Naito et al.,         12 months            Cystic -7 cm
2009 [55]                19 months            Solid - 1.8 cm
                         15 months            Solid - 1.7 cm

8. Nojima et al.,        No evidence of       Solid
1993 [56]                disease              Case 1 - 6.5 cm
                         (surveillance        Case 2 - 5 cm
                         32 months)
                         Second case died
                         after 8 month

10. Sakai et al.,        NM                   2 cm
2000 [57]                                     3.8 cm

11. Muraki et al.,       59.1%/5years         Mean size =
2016 [9]                                      5.3 cm
                                              60% cystic
                                              33% intraductal

12. Reid et al.,         From 1.7 to 21.18    Cystic/solid
2017 [26]                months               Mean size=
                                              4.96 cm
                                              (range from 2
                                              cm to 9 cm)

13. Luchini et al.,      OS = 20 months       NM
2017 [8]                 Pure UCOGC median    Intraductal
                         survival = 36        growth in 12
                         months               cases

14. Fukukura et al.,     NM                   Solid
2019 [58]                                     1 case cystic
                                              Maximum diameter
                                              between 2.6 -
                                              8.3 cm
                                              (mean = 4.4 cm)

Author                   Preneoplastic        Other invasive
                         lesion               carcinoma

1. Alguacil-Garcia       NM                   DC
et al., 1977 [2]

2. Deckard-Janatpour     NM                   9 cases UCPGC
et al., 1998 [50]

3. Hoorens et al.,       NM                   DC (both cases)
1998 [51]

4. Molberg et al.,       MCN 2 cases          DC 4 cases
1998 [52]                (origin point)

5. Chopra et al.,        No                   No
2007 [53]

6. Layfield et al.,      NM                   NM
2008 [54]

7. Naito et al.,         NM                   NM
2009 [55]

8. Nojima et al.,        NM                   DC and UCPGC both
1993 [56]                                     cases

10. Sakai et al.,        NM                   Well differentiated DC
2000 [57]                                     both cases

11. Muraki et al.,       4 cases arose        76% associated with
2016 [9]                 from MCN             DC
                         4 cases
                         associated with
                         18 cases with

12. Reid et al.,         No                  5 cases DC
2017 [26]                                    1 pure UCOGC
                                             1 case NM

13. Luchini et al.,      2 HG MCN            13 cases DC
2017 [8]                 1 HG IPMN
                         15 PanIN (12 HG
                         and 3 LG)

14. Fukukura et al.,     NM                  No
2019 [58]

Author                   Other aspects

1. Alguacil-Garcia
et al., 1977 [2]

2. Deckard-Janatpour     UCOGC 2 long term
et al., 1998 [50]        survivors

3. Hoorens et al.,       Same Ki-ras codon 12
1998 [51]                mutation identified
                         in both UC and DC

4. Molberg et al.,       Osteoid/bone - 3
1998 [52]                cases Chondroid - 1
                         case 1 case - 14
                         years survivor

5. Chopra et al.,        Osteoid - 1 case
2007 [53]

6. Layfield et al.,      EUS-FNA diagnosis
2008 [54]

7. Naito et al.,         EUS-FNA diagnosis
2009 [55]

8. Nojima et al.,        Case 2 - positive
1993 [56]                lymphnodes, liver
                         metastases after 8
                         months with UC

10. Sakai et al.,        No OGC harbor mutated
2000 [57]                K-ras found in PGC,
                         DC and mononuclear
                         tumor cells

11. Muraki et al.,       PanIN and OGC were
2016 [9]                 often intermingled

12. Reid et al.,         EUS-FNA diagnosed,
2017 [26]                6 cases underwent

13. Luchini et al.,      8 cases WES
2017 [8]

14. Fukukura et al.,     CT and MRI study
2019 [58]                with histopathology

Abbreviations: F-female; M-male; NM-not mentioned; DC-ductal
carcinoma; UCPGC-undifferentiated carcinoma with pleomorphic giant
cells; MPD-main pancreatic duct; CBD-common bile duct; CT-computer
tomography; MRI-magnetic resonance imaging; OS-overall survival;
WES-whole exome sequencing; EUS-FNA-endoscopic ultrasound fine
needle aspiration; IPMN-intraductal papillary mucinous neoplasm;
PanIN-pancreatic intraepithelial neoplasia; HG-high grade; LG-low
grade; CHA-common hepatic artery
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Title Annotation:Case report & Review
Author:Rusu, Andreea; Giusca, Simona Eliza; Apostol, Delia Gabriela Ciobanu; Ionescu, Lidia; Caruntu, Irina
Publication:Archive of Clinical Cases
Date:Mar 1, 2019
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