Acta Medica Mediterranea, 2019, 35: 1661

SIMULTANEOUS PRESENTATION OF AND OF PLASMACYTOMA

Liyan Chu1#, Ping Sui1#, Shujie Song1, Liangming Zhang1, Yanchun Wang1, Lingyan Zhao2* 1Department of Medical , The affiliated Yantai Yuhuangding Hospital of Qingdao University, P.R.China - 2Department of Nursing, The affiliated Yantai Yuhuangding Hospital of Qingdao University, P.R.China #Liyan Chu and PingSui contributed equally to this work ABSTRACT

Aim: To explore the clinicopathological features, auxiliary examination and diagnosis and treatment of patients with combined with non-Hodgkin’s , and to improve clinicians’ understanding of such double primary malignant tumors Methods: A case study of the clinical manifestation, auxiliary inspection, medical treatment and of a non-Hodgkin’s lymphoma patient in our hospital was reported. Conclusion: Currently with the improvement of the of cancer patients and the rapid development of and , the detection rate of multiple primary is increasing, but its etiology is still unclear, and the predi- lection sites are reported differently in different countries and districts. For example, stomach cancer is the most common cancer regarding to multi-primary cancer as reported in Japan, while in China, nasopharyngeal carcinoma, cancer, and breast cancer are main cancer types regarding to multi-primary cancer. It is very rare that stomach cancer is combined with plasmacytoma carcinoma.

Keywords: Double primary cancer, stomach cancer, plasmacytoma carcinoma, multiple primary cancer.

DOI: 10.19193/0393-6384_2019_3_260 Received November 30, 2018; Accepted February 20, 2019

Introduction one in the affiliate Yantai Yuhuangding Hospital of Qingdao University is reported as follows. Simultaneous dual-source primary tumor re- fers to different primary happening Clinical Information in different organs within same patient, which Patient is a 76 years old male retired worker who was proposed by Billroth in 1889. Among them, was admitted to the hospital on December 26 th, 2013 double primary carcinoma (DPC here after) is due to “full abdominal distension, pain and discom- named if there are two independent primary ma- fort for more than 20 days”. This symptom was not lignancies, and multiple primary carcinoma (MPC existed around 20 days ago prior to the admission to here after) is named if there are more than two the hospital. The pain was not heavy, and the specific independent primary malignancies. MPC is a rare nature was hard to explain. There were no other radi- phenomenon in oncogenesis, and the most com- ation pains in other body parts. There were no other mon MPC incidence organs are ones relating to accompanying symptoms such as acid reflux, heart- digestive systems and respiratory systems. burn, ,, , black stool etc. Although it is not uncommon that stomach The patient was diagnosed with gastric ulcer cancer is combined with other solid tumors in (specific nature to be determined) and atrophic gastri- DPC, it is rare that the other solid tumor is plas- tis (Gastric antrum) using gastroscopy in other hospi- macytoma carcinoma. Here a patient with stom- tal before admission. The gastroscopic showed ach cancer combined with plasmacytoma carci- partial inflammatory epithelial dysplasia in a small noma from medical oncology department section amount of inflammatory exudate of , 1662 Liyan Chu, Ping Sui et Al which meet the criteria of ulcerative cancer. plasmablastic lymphoma cannot be excluded. The pathological section had been sent to the The results of computed tomography (CT, pathology department of Peking University Third here after) on chest, upper abdomen and kidneys Hospital by patient and the results showed that the were as follows: epithelium of the tissue was covered, and visible • No abnormalities in chest scan exudation was seen on the surface while dysplas- • Cholecystitis and gallstones tic gland was diffused under the surface. Solid cell • Left renal hydronephrosis and upper ureteral nest and single scattered cells were visualized, as dilatation well as the tumor cell layer. • Paravertebral space occupying Differentiated with neu- roendocrine differentiation in a few cells was di- The physical examination results were as agnosed (Meeting L-2014-0036). Paravertebral follows: biopsy showed polymorphic tumor cell hyperpla- • Flat abdomen; sia in fibrous fat connective tissue, and rich cyto- • Pain with light pressure on upper abdomen; plasm with light pink dye in medium sized cells as • No sign of rebound pain in upper abdomen; well as polymorphism nucleus. Combining with • No touchable block in abdomen; the previous primary unit immunohistochemistry • Pain with knock on left kidney area; results, non-Hodgkin’s lymphoma and plasmacy- • Pain with press on left tibia. toma were diagnosed. This diagnosis results were The patient had no prior special medical his- supported by morphology as well as the protein tory before. The patient had a history of tobacco level. The patient was diagnosed with stomach and alcohol for around 30 years with around 30 cancer combined with plasmacytoma. Paraver - cigarettes and 200ml alcohol per day. A similar tebral placeholder radiotherapy was first used to medical history in close relatives was denied by treat stomach cancer, following by 2 cycles of the patient as well as the familial genetic history. mono- using oral Tiggio 40mg bid The patient lost around 5kg in body weight com- dl-14. After paravertebral placeholder radiothera- paring to a month ago. py, 4 cycles of chemotherapy with and Tiggio were used, and the condition was stable The laboratory diagnosis results after admis- (Stable Disease, SD) after 2 cycles. After 4 cycles sion were as follows: of chemotherapy treatment, chest enhanced CT Tumor test: was used and the results showed that the mass in • 1.90ng/ml, gly- right rear chest was bigger than the one in 2014- coprotein 1990.69U/ml, glycoprotein 7249.53U/ 06-27, which indicated that the disease was pro- ml, no abnormalities in other tests. gressing, and plasmacytoma was considered as Ultrasound test on neck: the reason causing this. Hence the chemotherapy • No enlarged lymph nodes were detected, In- contraindications were excluded and 2 cycles of guinal exploration and hypoechoic nodules showed CHOP chemotherapy treatment with Cyclophos- 0.6*0.4cm on right side and 0.8*0.4cm on left side. phamide 0.8d1, 180mgd1, Vincristine CDFI (Color Doppler Flow Imaging) test: 2mgd1 and Prednisone 5mgd1-5. PR was evaluat- • A little blood flow signal was detected inside. ed after 2 cycles of treatment, and 2 more cycles Gastroscopic biopsy test: of CHOP chemotherapy were used. The CT results • Stomach adenocarcinoma. showed that comparing to 2015-01-17, there were Paravertebral occupying space puncture bi- more double lung nodules and small shadows, and opsy test: the mass positioning between 4th and 5th right ribs • Atypical lymphoid cell infiltration was de- was bigger. tected in a few punctured tissues. The puncture on the mass in right chest in- Immunohistochemistry test: dicated of plasmacytoma. Considering • CD138 diffusion (+), CD38, MUM-1 dif- of the progress of the disease, the first cycle of fusion, CD30, EMA focality(+), CK(-), CD20(-), chemotherapy using Gemcitabine 1.2gd1, d8 and CD21(-), CD10(-), Bcl-6(-), κ, λ showing mono- Oxaliplatin 150mgd2 from 2015-03-25 was used. clonal , Ki-67>90%, high chance of The analysis results indicated abnormal re- plasmablastic plasmacytoma, and the possibility of nal function (Potassium: 5.38mmol/L, Chlorine: Simultaneous presentation of stomach cancer and carcinoma of plasmacytoma 1663

110.5mmol/L, Urea: 15.14mmol/L, Creatinine: The patient abandoned treatment for person- 224ummol/L) at the second cycle of chemother - al reasons and was discharged from hospital. In apy using Gemcitabine and Oxaliplatin. Symp- a telephone follow-up after 3 months, it was told tomatic supportive treatments such as improving that the patient had passed away (fig.1-2-3-4). kidney functions were applied.

Figure 1: Gastroscopic biopsy results: covered epithe- Figure 4: marrow biopsy results: No plasma cell lial; exudation on surface; diffuse infiltration of glandular proliferation. dysplasia below; solid cell nests and individual scattered cells as well as tumor cell layer. Diagnosis: Differentiated Discussion adenocarcinoma in the corpus and neuroendocrine diffe- rentiation in a few cells. (HE, ×100). Stomach cancer is one of the most common malignancies in digestive system, and its incidence ranks the third in malignant tumors (1-2). More than 1 million new cases of stomach cancer occur every year worldwide (1-2). Single-onset stomach cancer is common, but stomach cancer is not common with other malignant tumors (1-3). Plasmacytoma is a highly mature B-cell lymphoma that usually oc- curs in a single site of bone or soft tissue and is divided into solitary plasmacytoma and extramed- ullary plasmacytoma according to the location of the disease(4-5). Extramedullary plasmacytoma is a rare type Figure 2: Abdominal CT results: density shadow in the of malignant monoclonal plasma cell disease, waist 3-4 and para-aortic soft tissue. which originates from any organ other than bone marrow hematopoietic tissue, accounting for less than 2% of systemic plasmacytoma (4-6). The loca- tion of the disease is more common in the head and neck, and the age of onset is usually 50-60 years old with an average age of 55 years, and the ratio of male to female is 2:1 (1-6). The etiology of soli- tary plasmacytoma has not been established, and factors such as radiation, viral infection, genetic factors, stimulation of chronic antigens, and pro- longed exposure to certain chemical products are (1-5-7) Figure 3: Paravertebral space biopsy results: polymor- considered to be associated with disease . Its phic tumor cell hyperplasia in fibrous fat connective tis- onset is more insidious, with bone pain and local sue; rich cytoplasm with light pink dye in medium sized lumps as the main clinical manifestations, lasting cells; polymorphism nucleus; heterotypic lymphoid cell for a long time, ranging from several months to infiltration. Immunohistochemistry results: CD138 diffu- several years, usually not easy to attract attention. sion (+), CD38, MUM-1 diffusion, CD30, EMA focali- The disease can affect any bone in the body, ty(+), CK(-), CD20(-), CD21(-), CD10(-), Bcl-6(-), κ, λ but mainly that produce red pulp, especially showing monoclonal hyperplasia, Ki-67>90%. Diagno- vertebrae. sis: Plasmablastoma (HE, ×100). 1664 Liyan Chu, Ping Sui et Al

Malignant tumors in vertebrae are rare, and the Among the other cancers combined with stom- solitary plasmacytoma of the bone accounts for about ach cancer, stomach cancer combining with lung 30%(1-7). Other blood abnormalities, hypercalcemia cancer has been reported more common. Stomach and impaired renal function caused by bone marrow cancer combining with or gastric lym- invasion are also observed(3-6). This disease usually be- phoma has been reported many times (1-4-13). Case gins with insidious disease, has a long course, and has reports are more common in primary stomach no characteristic clinical symptoms and body signs, cancer combining with gastric mucosa-associated which may easily lead to misdiagnosis or missed diag- lymphoid tissue lymphoma, and stomach cancer nosis. Double primary carcinoma is also named mul- combing with plasmacytoma is rare. According to tiple primary carcinoma (MPC), which was first pro- statistics, the prognosis of most multiple cancers posed by Billroth in 1989. MPC refers to two or more is worse than that of single malignant tumors. The independent, unrelated primary malignant tumors reasons are related to factors such as late onset occurring simultaneously or sequentially in the same age, limited treatment methods and clinical super - organ, paired organs or different organs (1-8). In recent position of tumors. However, there are also clin- years, with the rapid development of medical imaging ical studies showing that the prognosis is related and pathology, and the increasing popularity of routine to the clinical stage of a single tumor, and there is physical examination, the detection rate of MPC has no significant difference in the overall survival rate also increased, and clinical reports are no longer rare. of multiple tumors (1-4-14). Here we report a case of The incidence of MPC reported in other countries is stomach cancer with plasmacytoma, and according about 2.3% - 10.7%(3-5-7). to the diagnostic criteria, this case belongs to the According to the interval time, multiple pri- simultaneous stomach and plasmacytoma dual pri- mary cancers are divided into two types: simul- mary carcinoma. taneous and metachronous. Multiple malignant Currently there is no standard treatment plan tumors happening within 6 months are called si- for MPC worldwide, and it is recommended that multaneous multiple primary malignant tumors, treatment should use the same principle as treating and tumors happening more than 6 months are single-shot tumor according to the specific condi- called heterogeneous multiple primary malignant tions of patients. The corresponding individual- tumors(1-4). Simultaneous dual-source primary tum- ized treatment plan should be made according to ors refer to different histologically primary malig- the extent of tumor involvement, clinical stage and nant tumors happening in different locations at the pathological type to reach the goal of cure. In this same time in the same patient. case, the patient was diagnosed with stomach can- cer after the laboratory and auxiliary examination The diagnostic criteria are as follows: for the reason of upper abdominal discomfort. Dur- • The tissue cytology of each tumor must be ing the examination, paravertebral space occupying malignant; was detected, and hematological malignant tumor • The pathological morphology and immun- - plasmacytoma was also diagnosed. The initial ochemistry characteristics of each tumor must be symptom of the patient was abdominal discomfort, different; and paravertebral radiotherapy and stomach cancer • The possibility of metastasis must be exclud- anti-tumor chemotherapy treatments were used, but ed. The pathogenesis of MPMN is still unclear and the disease progressed rapidly. may be related to immune function defects, genet- Considering the activity of the plasmacytoma, ics, host susceptibility, , environ- 2 cycles of CHOP chemotherapy were adopted, ment, smoking etc(1-9). and parts of the evaluation were relived. However, The predilection sites of MPC are mainly na- the disease progressed again soon. Considering the sopharyngeal carcinoma, lung cancer, colorectal combination of multiple cancers, the tumor activ- cancer, breast cancer and in China. ity in vivo was high and progressed rapidly. The According to the literature, the incidence of MPC specific etiology of simultaneous multiple prima- in stomach cancer patients is about 3.4%, and the ry cancers has not been clarified, but according to most common primary site is colorectal, which ac- worldwide research reports, simultaneous multi- counts for 37.2%, followed by primary lung cancer ple primary cancers have significantly higher ma- (18.6%), (16.8%) and primary lignancy, less effective anti-tumor treatment and (9.7%)(1-10-12). shorter expected lifetime comparing to single tu- Simultaneous presentation of stomach cancer and carcinoma of plasmacytoma 1665 mor(1-14-15). MPC may be caused by multiple onco- 15) Ono, S., et al., Metachronous gastric cancer following in patients, and broad-spectrum anti-tumor complete remission of gastric MALT lymphoma. Ann Oncol, 2009. 20(10): p. 1748-9. drugs and multi-target anti-angiogenic drugs can be 16) Hamaloglu E., et al., Synchronous and metachronous (1-4-16) used in the treatment of MPC patients . occurrence of gastric adenocarcinoma and gastric lym- phoma: A review of the literature. World J Gastroenter- ol, 2006. 12: 3564-3574.

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