Recurrent Chemotherapy Treated Indeterminate Dendritic Cell Tumor: Case Report and Literature Review

Figures & data

Figure 1 (A–C) Skin condition before and after treatment. Upon admission, multiple yellowish-red or reddish-brown papules and nodules almost spread throughout the body, with clear boundaries and partial fusion. The back area was the most severe (A). After the completion of 4 courses of CHOP+ lenalidomide, the rash subsided significantly, with significant pigmentation on the back (B). Two courses of chemotherapy were completed after recurrence, and the rash almost completely subsided with only a small amount of pigmentation on the back (red arrow, biopsy scar after recurrence) (C). (D) [18F] FDG-PET/CT showed considerable metabolic increases in the skin (the red arrows point to some areas exhibiting heightened metabolic activity). Areas including the upper limbs (upper arm), lower neck, body (back), and the skin/subcutaneous area of the upper thighs of both sides within the detection range, and some of them were accompanied by small nodular shadows. The possibility of malignant tumor lesions was considered. Immunohistochemical studies demonstrated that the histiocytes were positive for CD1a (E), CD68 (F) and S-100 (G) and negative for Langerin (H).

Figure 2 The timeline of this case report.

Abbreviations: CTX, Cyclophosphamide; DOX, doxorubicin; VDS, Vindesine; DEX, dexamethasone; LOHP, Oxaliplatin; GEM, Gemcitabine; NA, not available.

Table 1 Reported Cases of IDCT with Cutaneous Symptoms Treated with Chemotherapy Medications

Author (Year)	Gender	Age	Presentation: MF/SF	NGS	Mutation Detected	Extracutaneous Involvement	Treatment	Outcome	FU(Mo)	Reference
Wood (1985)	Female	25	MF	No		No	1. Steroid injections; 2. vinblastine sulfate	Did well with treatment once a month (4 y); flare-up without treatment; 33 mo without recurrence. RR then CR	114	[1]
Kolde (1985)	Male	36	MF	No		MastCL	Vincristine, daunorubicin hydrochloride (Daunoblastina), and asparaginase	DOD	72	[26]
Segal (1991)	Male	29	MF	No		FL, AML	1. Lomustin; 2. carmustine; 3. CTX, vincristine, and prednisone; 4. CTX, doxorubicin, VP-lb/cytarabine, vin- cristine, methotrexate with leucovorin, bleomycin, and pred- nisone	DOD	45	[27]
Flores-Stadler (1999)	M	0	MF	No		Bone marrow	CTX, doxo-rubicin, vincristine, and prednisone	DOD	20	[28]
Rodriguez-Jurado (2003)	F	13	MF	No		No	Pure coal tar and 5% 5-FU cream	PR		[29]
Caputo (2005)/case 1	Male	32	MF	No		No	1. CTX; 2. etoposide; 3. Vinylsulfatase and Methylprednisolone; 4.2-Chlorodeoxyadenosine	Experienced remission and relapse processes during treatment and finally induced a complete remission after 4-year treatment. RR then CR	48	[25]
Caputo (2005)/case 2	Male	36	MF	No		No	1. CTX; 2. etoposide; 3. acelastine and methylprednisolone	Experienced remission and relapse processes during treatment, currently without therapy and free of lesions. RR then CR	60	[25]
Vener (2007)	Male	39	MF	No		AML	1. Oral CTX; 2. etoposide(iv); 3. vinblastin and ethylprednisolone	Repeated remission and recurrence; the fourth year was diagnosed of AML and died of acute respiratory failure that year. RR then DOD	48	[11]
Yin (2009)	Female	30	MF	No		No	Thalidomide and isotretinoin	The lesion disappeared within 1 year; follow-up after 3 years without recurrence. CR	48	[22]
Cheuk (2009)	Female	44	MF	No		No	1. CTX, epirubicin, vincristine and prednisone; 2. VM-26 and vinblastine; 3. herbal medicine; 4. etoposide	Responded quite dramatically to chemotherapy, and relapse often occurred on cessation of therapy: SD with RR	120	[24]
Ventura (2010)	Male	62	MF	No		No	Thalidomide	2 months: gradual regression; 7 months: almost complete remission; 1 month after remission: diagnosed of an acute monocytic leukemia and died 1 month later due to a respiratory failure. DOD	10	[23]
Tóth (2011)	Male	15	MF	No		No	1. 5-FU, repeatedly cryotherapy and cauterization: ineffective; 2. transfer to thalidomide	8 months: healed with pigmentation; 3 years: without recurrence. PR	44	[20]
Ozono (2011)	M	1	MF	No		JMML	1. vincristine, Ara-C, and prednisolone; 2. 6MP; 3. HSCT	PR	9	[30]
Fournier (2011)	Female	65	MF	No		No	MTX	Complete clinical remission after 2 months of treatment, relapse during dose reduction:SD with RR	5	[5]
Bettington (2011)	Male	40	MF	No		FL, lymph nodes	Multiple regimens to treat FL: CVP,CVP-R and CHOP	4 months after diagnosed with IDCT, he died due to the development of end-stage liver disease, which limited the treatment.:DOC	4	[21]
Chen (2018)	Male	31	MF	N0		No	MTX, no response, transfer to isotretinoin and thalidomide	Improvement on skin, under follow up: SD	48	[17]
Zhou (2019)	Male	37	MF	Yes	No	No	Corticosteroids, vinca alkaloids, CTX	Utilizing a range of treatments, yet constantly experiencing remission and relapse within 5 years. SD with RR	60	[16]
Fischer (2021)	Female	55	MF	No		No	Thalidomide	6 months: lesion progress:PD	6	[15]
Xu (2017)	M		MF	No		No	Thalidomide	PR	10	[18]
Xu (2017)	F	53	MF	No		No	Methotrexate	CR	10	[18]
Xu (2017)	M		MF	No		No	Methotrexate	CR	10	[18]
Xu (2017)	F		MF	No		No	Thalidomide	PR	10	[18]
Lie (2022)	Male	70	MF	No		No	Initial treatment with psoralen and PUVA for 4 months: ineffective transfer to MTX	6 months: significant improvement:PR	10	[13]
Belina (2022)	Female	62	MF	Yes	ETV3-NCOA2	No	MTX and NBUVB	Sustained improvement in cutaneous lesions:PR		[14]
Xia (2022)	Female	26	MF	Yes	No	No	Thalidomide followed by prednisolone	Resistant to treatment:SD	36	[12]
Li (2022)	Female	47	MF	No		No	CHOP plus lenalidomide/ thalidomide; Oxaliplatin, Gemcitabine and Betamethasone	Remission and recurrence during CHOP, lesion is regressing with another chemotherapy. SD with RR	12

Abbreviations: MF, multi focal; SF, single focal; FU, follow up months; CMML, chronic myelomonocytic leukemia; FL, follicular lymphoma; CTX, cyclophosphamide; 5-FU, 5-fluorouracil; MTX, methotrexate; CVP/CVP-R, cyclophosphamide, vincristine and prednisone plus or minus rituximab; CHOP, cyclophosphamide, hydroxydaunorubicin, vincristine and prednisone; PUVA, Psoralen and ultraviolet light A; NBUVB, Narrowband ultraviolet B; 6MP, 6-mercaptopurine; HSCT, stem cell transplantation; CR, complete remission; PR, partial remission; RR, remission and relapse; DOD, dead of disease; DOC, dead of other cause; PD, progressive disease.

Wood GS, Hu CH, Beckstead JH, Turner RR, Winkelmann RK. The indeterminate cell proliferative disorder: report of a case manifesting as an unusual cutaneous histiocytosis. J Dermatol Surg Oncol. 1985;11(11):1111–1119. doi:10.1111/j.1524-4725.1985.tb01399.x

 PubMedGoogle Scholar

Kolde G, Brocker EB. Multiple skin tumors of indeterminate cells in an adult. J Am Acad Dermatol. 1986;15(4 Pt 1):591–597. doi:10.1016/s0190-9622(86)70209-0

 PubMed Web of Science ®Google Scholar

Segal GH, Mesa MV, Fishleder AJ, et al. Precursor Langerhans cell histiocytosis. An unusual histiocytic proliferation in a patient with persistent non-Hodgkin lymphoma and terminal acute monocytic leukemia. Cancer. 1992;70(2):547–553. doi:10.1002/1097-0142(19920715)70:2<547::aid-cncr2820700227>3.0.co;2-z

 PubMed Web of Science ®Google Scholar

Flores‐Stadler EM, Gonzalez‐Crussi F, Greene M, Thangavelu M, Kletzel M, Chou PM. Indeterminate‐cell histiocytosis: immunophenotypic and cytogenetic findings in an infant. Med Pediatr Oncol. 1999;32(4):250–254. doi:10.1002/(sici)1096-911x(199904)32:4<250::Aid-mpo2>3.0.Co;2-#

 PubMedGoogle Scholar

Rodriguez-Jurado R, Vidaurri-de la Cruz H, Duran-Mckinster C, Ruiz-Maldonado R. Indeterminate cell histiocytosis. clinical and pathologic study in a pediatric patient. Arch Pathol Lab Med. 2003;127(6):748–751. doi:10.5858/2003-127-748-ICH

 PubMed Web of Science ®Google Scholar

Caputo R, Marzano AV, Passoni E, Bellinvia M. Chemotherapeutic experience in indeterminate cell histiocytosis. Br J Dermatol. 2005;153(1):206–207. doi:10.1111/j.1365-2133.2005.06644.x

 PubMed Web of Science ®Google Scholar

Vener C, Soligo D, Berti E, et al. Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia. Br J Dermatol. 2007;156(6):1357–1361. doi:10.1111/j.1365-2133.2007.07880.x

 PubMed Web of Science ®Google Scholar

Yin R, Zheng WJ, Yang XC, Hao F. Recurrent generalized indeterminate cell histiocytosis: a case report. J Am Acad Dermatol. 2010;63(1):e3–5. doi:10.1016/j.jaad.2009.10.010

 PubMedGoogle Scholar

Cheuk W, Cheung FY, Lee KC, Chan JK. Cutaneous indeterminate dendritic cell tumor with a protracted relapsing clinical course. Am J Surg Pathol. 2009;33(8):1261–1263. doi:10.1097/PAS.0b013e3181a0cd38

 PubMed Web of Science ®Google Scholar

Ventura F, Pereira T, da Luz Duarte M, Marques H, Pardal F, Brito C. Indeterminate cell histiocytosis in association with acute myeloid leukemia. Dermatol Res Pract. 2010;2010:569345. doi:10.1155/2010/569345

 PubMedGoogle Scholar

Tóth B, Katona M, Hársing J, Szepesi A, Kárpáti S. Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide. Pathol Oncol Res. 2012;18(2):535–538. doi:10.1007/s12253-011-9405-8

 PubMed Web of Science ®Google Scholar

Ozono S, Inada H, Nakagawa SI, et al. Juvenile myelomonocytic leukemia characterized by cutaneous lesion containing Langerhans cell histiocytosis-like cells. Int J Hematol. 2011;93(3):389–393. doi:10.1007/s12185-011-0787-x

 PubMed Web of Science ®Google Scholar

Fournier J, Ingraffea A, Pedvis-Leftick A. Successful treatment of indeterminate cell histiocytosis with low-dose methotrexate*. J Dermatol. 2011;38(9):937–939. doi:10.1111/j.1346-8138.2010.01148.x

 PubMed Web of Science ®Google Scholar

Bettington A, Lai JK, Kennedy C. Indeterminate dendritic cell tumour presenting in a patient with follicular lymphoma. Pathology. 2011;43(4):372–375. doi:10.1097/PAT.0b013e32834685b7

 PubMed Web of Science ®Google Scholar

Chen C, Nguyen GH, Zeng YP. Indeterminate cell histiocytosis presenting with leonine facies. Acta Derm Venereol. 2018;98(4):463–464. doi:10.2340/00015555-2866

 PubMed Web of Science ®Google Scholar

Zhou N, Ge Y, Fang K, et al. BRAF wild-type recurrent indeterminate dendritic cell tumour presenting with leonine facies. J Eur Acad Dermatol Venereol. 2020;34(5):e230–e31. doi:10.1111/jdv.16172

 PubMed Web of Science ®Google Scholar

Fischer AS, Zaladonis AG, Subrt P, Tschen J, Hsu S. Indeterminate cell histiocytosis mimicking rosacea. Cureus. 2021;13(1):e12850. doi:10.7759/cureus.12850

 PubMed Web of Science ®Google Scholar

Xu XL, Bu WB, Zong WK, Sun JF. Indeterminate cell histiocytosis: a case series and review of the literature. Eur J Dermatol. 2017;27(5):559–561. doi:10.1684/ejd.2017.3121

 PubMed Web of Science ®Google Scholar

Lie E, Jedrych J, Sweren R, Kerns ML. Generalized indeterminate cell histiocytosis successfully treated with methotrexate. JAAD Case Rep. 2022;25:93–96. doi:10.1016/j.jdcr.2022.05.027

 PubMedGoogle Scholar

Belina ME, Kwock JT, Al-Rohil R, Fresco A. An atypical myelomonocytic cell infiltrate: use of next-generation sequencing to diagnose indeterminate cell histiocytosis. Am J Dermatopathol. 2022;44(7):529–531. doi:10.1097/dad.0000000000002167

 PubMed Web of Science ®Google Scholar

Xia DM, Zhou QT, Wang L. Typical leonine facies in a patient with indeterminate dendritic cell tumor. Int J Dermatol. 2022;62(1):128–129. doi:10.1111/ijd.16106

 PubMed Web of Science ®Google Scholar