ISSN:(O) 2320-5407, ISSN(P) 3107-4928 Int. J. Adv. Res.

13(11), November-2025, 169-177

Journal Homepage: - www.journalijar.com

Article DOI:10.21474/IJAR01/22101
DOI URL: http://dx.doi.org/10.21474/IJAR01/22101

RESEARCH ARTICLE

CENTRAL DIABETES INSIPIDUS REVEALING A MULTISYSTEM LANGERHANS

CELL HISTIOCYTOSIS : A CASE REPORT
Zineb Serhane1, Meryem El Adla1, Zineb EL Azime1,2, Mohammed-Amine Essafi1,2, Hayat Aynaou1,2 and
Houda Salhi1,2

1. Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition. Hassan II University Hospital
Center. Fez. Morocco.
2. Laboratory of Epidemiology, Research in Health Sciences, Faculty of Medicine and Pharmacy, USMBA, Fez,
Morocco.
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Introduction: Langerhans Cell Histiocytosis (LCH) is a rare myeloid
Received: 04 September 2025 precursor disorder primarily affecting young individuals, in which
Final Accepted: 06 October 2025 hypothalamic-pituitary involvement is uncommon but often
Published: November 2025 diagnostically challenging due to non-specific clinical and radiological
features.
Key words:-
Langerhans cell histiocytosis; Case report: We present the case of a 22-year-old woman referred for
Multisystem disease; Hypothalamo- evaluation of sudden-onset polyuro-polydipsic syndrome and
pituitary involvement; secondary amenorrhea. MRI revealed a thickened pituitary stalk, and
Central diabetes insipidus;
biochemical investigations confirmed central diabetes insipidus and
Hypopituitarism; Histological diagnosis,
Hypothalamo-pituitary MRI, anterior pituitary hormone deficiencies. Skin lesions observed on
examination were biopsied and underwent histopathological and
immunohistochemical analysis, revealing findings consistent with LCH
(CD1a+, CD68+, S100+, and CD34-). Subsequent work-up revealed
multisystemic involvement including hematologic, hepatic, pulmonary,
osseous,and lymphatic manifestations.
Despite initiation of corticosteroid therapy and consideration for
systemic chemotherapy, the patient developed fatal septic shock.
Conclusion : This case highlights the diagnostic value of skin biopsy
in inaccessible lesions and the importance of early diagnosis and
multidisciplinary intervention in aggressive multisystemic LCH.

"© 2025 by the Author(s). Published by IJAR under CC BY 4.0. Unrestricted use allowed
with credit to the author."
……………………………………………………………………………………………………....
Introduction:-
Langerhans Cell Histiocytosis (LCH), also known as Histiocytosis X or Hand-Schüller-Christian Syndrome, is a rare
disorder of the reticuloendothelial system characterized by the clonal proliferation of Langerhans cells; myeloid
progenitor cells that share phenotypic features with epidermal dendritic cells [1]. LCH primarily affects children and
young adults and presents with a highly variable course, with mortality rates reaching up to 80% in case of advanced
multisystem involvement [2]. Neurological manifestations are relatively rare with a predilection for the
hypothalamic-pituitary axis [3]. The involvement of the sellar region is difficult to diagnose due to non-specific

Corresponding Author:- Zineb Serhane 169

Address:-Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition. Hassan II
University Hospital Center. Fez. Morocco.
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findings and limited access to pituitary tissue, making histological analysis of accessible lesions crucial for diagnosis
and treatment planning. We report the case of a young woman whose initial presentation of LCH involved the
pituitary gland and was subsequently confirmed by immunohistochemical and histopathological analysis of a skin
lesion. The disease evolved rapidly to multisystem involvement and culminated in fatal multiorgan failure. This case
underscores the critical importance of early diagnosis and comprehensive systemic evaluation in patients with
suspected LCH.

Case Report:
A 22-year-old female patient was referred to the Endocrinology Department at Hassan II University Hospital in Fez
for etiological investigation of a sudden-onset polyuria-polydipsia syndrome associated with secondary amenorrhea
evolving over a period of six months. History-taking revealed additional symptoms including chronic headaches and
changes in vision suggestive of a pituitary tumor syndrome, alongside asthenia and an unintentional weight loss of 7
kilograms over six months. On clinical examination, the patient had a low body mass index (BMI) of 16 kg/m². She
exhibited a severe polyuria-polydipsia syndrome (PPS) with 24-hour fluid intake of 12 liters and urine output of 13
liters. Dermatological examination revealed multiple small erythematous papules and seropapules on the trunk,
which were non-painful and non-pruritic, along with subcentimetric vesicles and occasional pustular lesions. Breast
examination showed no spontaneous or provoked galactorrhea, with Tanner stage V.

Figure 1 : clinical images of the patient showing multiple small erythematous papules and seropapules

After ruling out common causes of PPS, laboratory investigations revealed a biochemical profile consistent with
diabetes insipidus: low urinary osmolality at 190 mOsm/kg, borderline high plasma osmolality at 296 mOsm/kg, and
a serum sodium concentration of 143 mmol/L. For her secondary amenorrhea, a gonadotropic hormonal workup was
also performed, revealing hypogonadotropic hypogonadism. Complete pituitary hormonal assessment showed
associated corticotropic and somatotropic insufficiency, along with moderate hyperprolactinemia likely due to
pituitary stalk disconnection. Given the biological profile suggestive of diabetes insipidus and gonadotropic
insufficiency, a hypothalamic-pituitary MRI was performed. It revealed a spontaneously hyperintense nodular
thickening of the pituitary stalk, with homogeneous enhancement after contrast injection. The lesion measured 15 ×
15 × 18 mm (anteroposterior × transverse × height), suggesting a tumoral origin such as a dysgerminoma or a
granulomatous process. All these findings supported the diagnosis of central diabetes insipidus.

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A1 A2

B1 B2
Figure 2: Coronal (A) and sagittal (B) section of T1-weighted (1) and post-gadolinium T1-weighted (2) MRI
images of the patient showing a nodular thickening of the pituitary stalk, spontaneously hyperdense, with
homogeneous enhancement following contrast administration (performed at Hassan II University Hospital,
Fez, Morocco)

Ophthalmologic evaluation performed to assess for intracranial involvement revealed bilateral stage 1 papilledema,
with no abnormalities on Goldman-type visual field testing. The etiological workup conducted in the context of
pituitary stalk thickening revealed bicytopenia, consisting of normochromic, normocytic, non-regenerative anemia
and leukopenia with agranulocytosis and lymphopenia, without circulating blasts. This was associated with a
significant biological inflammatory syndrome, but no other paraclinical abnormalities suggestive of a tumoral or
granulomatous cause (Table 2).

Table 1 : Etiological Workup in the Presence of Pituitary Stalk Thickening

Investigations for Germinoma:
Tumor markers:
 Serum alpha-fetoprotein (AFP) and free beta-human chorionic gonadotropin (β-hCG):
Negative
 Cerebrospinal fluid (CSF) AFP and free β-hCG: Negative
Investigations for Sarcoidosis :
Complete blood count (CBC):
 Hemoglobin: 8.7 g/dL
 Mean corpuscular volume (MCV): 82 fL
 Mean corpuscular hemoglobin concentration (MCHC): 32 g/dL
 Hematocrit: 17%
 White Blood Cell Count (WBC): 1.15 × 10^9/L
 Neutrophils: 0.23 × 10^9/L
 Lymphocytes: 0.74 × 10^9/L
 Platelets: 245 × 10^9/L

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Iron studies:
 Serum iron: 0.35 mg/L (reference range: 0.6–1.8 mg/L)
 Ferritin: 136 µg/L (reference range: 10–120 µg/L)
Peripheral blood smear:
 No blasts
 Anisochromia
 Leukocyte differential confirmed on smear
Inflammatory markers:
 Erythrocyte sedimentation rate (ESR), 1st hour: >120 mm/h
 C-reactive protein (CRP): 17 mg/L
 Procalcitonin: 0.04 ng/mL
Serum protein electrophoresis (SPEP):
 Hypoalbuminemia
 Increased alpha-1 globulins
 Polyclonal hypergammaglobulinemia, suggesting an inflammatory or autoimmune process
Angiotensin-converting enzyme (ACE) level: 14.04 IU/L (reference range: 8–52 IU/L)
Thoracic CT scan:
 No radiological findings suggestive of sarcoidosis
Tuberculosis Workup:
Three sputum samples for acid-fast bacilli (AFB): Negative
Chest X-ray: No abnormalities detected

From a therapeutic standpoint, the patient was started on hormone replacement therapy. Desmopressin was
administered at a dose of 120 µg/day for the treatment of central diabetes insipidus, leading to the resolution of
polyuria–polydipsia syndrome. Hydrocortisone was also prescribed at 20 mg/day to address corticotropic
insufficiency. Growth hormone and gonadotropic deficiencies were not substituted at this stage, pending the
exclusion of an underlying neoplastic process.

The patient was subsequently referred to the Department of Internal Medicine for further evaluation of hematologic
abnormalities. Initial bone marrow aspiration revealed a hypercellular marrow infiltrated by 28% blasts, raising
suspicion for acute myeloid leukemia. However, a repeat bone marrow aspiration followed by a core biopsy
demonstrated a hypercellular marrow with granulocytic hypoplasia, erythroblastic hyperplasia, and features of
dysplasia. The blast population comprised of 18% undifferentiated cells and immunophenotyping revealed 7%
myeloid blasts expressing markers of immaturity (CD34+, CD38+, HLA-DR+, CD45+), which were suggestive of a
myelodysplastic syndrome (MDS).

Given the suspicion of a multisystem inflammatory disease and the inaccessibility of the pituitary region for biopsy,
a skin biopsy was performed. Histological examination revealed skin tissue lined by an acanthotic epidermis with
overlying ortho- and parakeratotic hyperkeratosis. The papillary dermis showed a moderate lymphocytic
inflammatory infiltrate along with a sheet of large oval cells exhibiting eccentrically placed, occasionally kidney-
shaped nuclei and abundant eosinophilic cytoplasm. Immunohistochemistry demonstrated positivity for CD1a,
CD68, and S100, and negativity for CD34. These histopathological and immunohistochemical findings were
consistent with a diagnosis of Langerhans cell histiocytosis.

A systemic workup was subsequently performed to assess for multisystem involvement. In addition to the
previously identified pituitary, hematologic, and cutaneous manifestations, the assessment revealed hepatic
involvement with hepatomegaly, interstitial lung disease mainly in the apices, and bilateral lymphadenopathy in
cervical, axillary, and inguinal regions.

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Figure 3: Axial section of a parenchymal window of contrast enhanced CT scan image showing interstitial
lung pattern, predominantly affecting the apical regions (performed at Hassan II University Hospital, Fez,
Morocco)

Figure 4 : Coronal reconstruction of a contrast enhanced abdominal CT scan revealing hepatomegaly

(hepatic arrow at 18 cm) (performed at Hassan II University Hospital, Fez, Morocco)

Following completion of the diagnostic workup, a diagnosis of multisystem Langerhans cell histiocytosis was
established, with involvement of risk organs, including the bone marrow and liver. The patient was started on
prednisone at a dose of 1 mg/kg/day and was considered a candidate for vinblastine-based chemotherapy. However,
the disease progressed rapidly, and her clinical condition deteriorated. She developed a refractory sepsic shock
originating from a cutaneous infection, secondary to a Klebsiella pneumonia, which ultimately resulted in death. The
exact cause of death could not be confirmed, as no autopsy was performed.

Discussion:-
Langerhans Cell Histiocytosis (LCH) is a rare disease characterized by the abnormal clonal proliferation of myeloid
precursors that differentiate into Langerhans cells (CD1a+/CD207+), which are related to antigen-presenting
dendritic cells normally found in the epidermis [1]. The exact pathophysiological mechanisms of LCH remain
unclear; however, environmental, infectious (e.g., HHV-6), immunological, and genetic factors have been suggested
[1]. Initially considered an inflammatory disorder secondary to immune dysregulation, LCH is increasingly
recognized as a malignant hematologic disease [4], particularly following the identification of somatic oncogenic
mutations. The most well-known of these involves the BRAF V600E mutation, which encodes an activated protein
kinase. Other mutations have been identified in genes of the MAPK–ERK signaling pathway, including MAP3K1,
KRAS, MAP2K1, MAPK/ERK, ARAF, HRAS, NRAS, and ERBB3 [5]. Understanding these mutations is essential,
as they carry significant therapeutic implications, particularly regarding the use of targeted therapies [6].

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Langerhans cell histiocytosis (LCH) predominantly affects children, with adult cases accounting for approximately
30% of the total [1]. The estimated incidence is 0.54 to 0.9 per 100,000 children per year and 1 to 2 cases per million
adults annually [7]. The disease shows a male predominance, with a peak incidence occurring between the ages of
33 and 40 years in adults, and between 1 and 3 years in children [7]. Clinically, LCH is highly heterogeneous,
ranging from isolated bone lesions—such as eosinophilic granuloma, to severe multisystem involvement with organ
dysfunction, as seen in Letterer–Siwe disease. The current classification system for adult LCH is based on the
number of lesions, the number of organs or systems involved, and whether high-risk organs are affected (e.g., liver,
spleen, or bone marrow) [3].

Table 2 : Classification of Langerhans Cell Histiocytosis in Adults [3]

Subtype Definition
Unifocal Single lesion involving one organ
Multifocal single-system disease Multiple lesions within a single organ
Multisystem disease Involvement of two or more organs/systems
- Withoutrisk-organinvolvement
- Withrisk-organinvolvement (liver, spleen, or bone marrow)

In adults, Langerhans cell histiocytosis (LCH) is rare and often presents with non-specific symptoms, leading to
delayed diagnosis. In adults, the most commonly affected sites include the bones (57%), lungs (58%), skin (36%),
and pituitary gland (29%), whereas hepatic, splenic, lymph node, and extensive skeletal involvement are more
frequently observed in pediatric cases [8]. Pulmonary involvement typically appears as reticulonodular infiltrates
with cystic changes, while skin lesions are highly variable in form. Hematopoietic and lymphoreticular involvement,
though less common, can include lymphadenopathy, hepatosplenomegaly with functional impairment, and bone
marrow infiltration causing cytopenias [1].

Involvement of the hypothalamic–pituitary axis (HPA) is among the most frequent manifestations of Langerhans
cell histiocytosis (LCH), with an incidence ranging from 40% to 70% depending on the series [9]. It represents the
most common endocrine and neurologic complication of the disease, occurring more frequently in multisystem
forms [8], as was the case with our patient. HPA involvement typically presents as central diabetes insipidus (CDI),
reported in approximately 25% of cases [10]. CDI may be the initial manifestation of LCH, as observed in our
patient, or may precede or follow the diagnosis by several years [3]. It can remain isolated or occur alongside other
anterior pituitary hormone deficiencies (APHDs), either concomitantly, as in our case, or subsequently [3]. These
deficiencies are often irreversible and have been reported in up to 94% of cases in some series [10].

Among the APHDs, growth hormone deficiency is the most common (40%–67%), followed by gonadotropin
deficiency (33%–58%). Adrenocorticotropic and thyrotropic deficiencies are less common (11%–30%), typically
presenting as part of a panhypopituitarism picture [10, 11]. Disconnection hyperprolactinemia is also observed in
approximately 20% of cases [10, 11]. The underlying mechanisms of these deficiencies may include direct
infiltration of the hypothalamic–pituitary region, autoimmune destruction mediated by anti-pituitary antibodies,
vascular injury with microlesions leading to hypoperfusion and fibrosis, or cytokine-mediated effects from adjacent
osseous lesions [12]. Our patient exhibited an endocrine pattern consistent with published data, except for the
absence of thyrotropic deficiency. She also presented with a pituitary mass syndrome, a manifestation that is
frequently reported in the literature.

More rarely, LCH may present as a hypothalamic syndrome, with symptoms such as hyperphagia and secondary
obesity, thermoregulatory disturbances, sleep and behavioral disorders, as well as cognitive, memory, and thirst
regulation deficits (adipsia), all of which significantly complicate therapeutic management [11]. Radiologically,
Langerhans cell histiocytosis (LCH) involving the hypothalamic–pituitary axis most commonly presents as
thickening of the pituitary stalk (seen in approximately 70% of cases), often associated with loss of the posterior
pituitary bright spot on T1-weighted MRI [13]. Less frequently (8–18% of cases), it may manifest as pseudo-
tumoral lesions of the pituitary, hypothalamic involvement, or even an empty sella syndrome [13]. It is important to
note that none of these findings are specific, and nearly 50% of patients with LCH-related hypopituitarism show no
detectable abnormalities on hypothalamic–pituitary MRI, suggesting other underlying mechanisms [14]. Pineal
gland thickening or cyst formation has also been reported more frequently in patients with LCH, although it
typically occurs without significant functional impairment in melatonin secretion [15].

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Due to the non-specific nature of clinical, biochemical, and radiological findings, definitive diagnosis of LCH
involving the hypothalamic–pituitary axis relies on histological confirmation. This entails identification of
Langerhans cell infiltration, characterized by histiocytes with pale eosinophilic cytoplasm, irregular "coffee bean–
shaped" nuclei with nuclear grooves, fine chromatin [3,9]. On electron microscopy, Birbeck granules may be
observed. Immunohistochemically, these cells express CD1a, S100, and CD207 (langerin) [1, 3, 9]. However, due to
the inaccessibility of the pituitary region, the small size of lesions, and the potential morbidity of biopsy, pituitary
biopsy is rarely performed and should be considered on a case-by-case basis [3]. It is typically indicated in the
presence of an expansive pseudo-tumoral mass or a pituitary stalk thickening >7 mm with no evidence of
extrapituitary involvement. In multisystemic disease, the diagnosis is usually established based on histopathological
features observed in other affected tissues [1,3], as was the case in our patient, where the diagnosis was confirmed
through skin biopsy.

The search for the BRAF V600E mutation is now systematically performed in all patients with LCH, either on
biopsy specimens or through blood and/or urine testing [3]. This mutation is present in over 50% of cases and is
associated with higher relapse rates and multisystem disease [3]. It carries major therapeutic implications,
particularly with the recent development of targeted therapies such as BRAF inhibitors [3]. Once the diagnosis of
Langerhans cell histiocytosis (LCH) is confirmed histologically, a thorough assessment of disease extent is essential,
as it determines both therapeutic strategy and prognosis. The diagnostic workup is guided by initial clinical findings
and first-line laboratory or imaging results [3].

It is recommended that all patients with confirmed or suspected LCH undergo a whole-body 18F-FDG PET/CT
scan, not only to assess disease dissemination and identify potential biopsy sites, but also to evaluate therapeutic
response. In HLCH, PET/CT appears to be more sensitive and detects lesions earlier than MRI in many cases [1,3].
Staging also allows for the detection of coexisting malignancies, which have been reported at increased frequency in
LCH patients. Several studies have demonstrated a higher incidence of hematologic malignancies, particularly acute
myeloid leukemia (AML), but also chronic myeloid leukemia, other myeloproliferative neoplasms, and lymphomas.
Solid tumors—such as lung and thyroid cancer—have also been reported [16, 17]. This was the case in our patient,
who initially presented with a myeloid proliferative state on bone marrow aspiration, raising suspicion for AML.
Although AML was ultimately ruled out, a myelodysplastic syndrome was diagnosed, an association that remains
very rare [16, 17].

Following the staging evaluation in our case, a diagnosis of multisystem LCH was established, with involvement of
the pituitary gland, skin, lungs, and lymph nodes, along with risk organ involvement (liver and bone marrow), which
is associated with a poorer prognosis [13].The management of Langerhans cell histiocytosis (LCH) depends
primarily on the patient’s age, the extent and distribution of lesions (focal vs. multisystem), and the presence of risk
organ involvement. Active surveillance or local therapy, including surgical excision, topical corticosteroids, or
radiotherapy, is generally recommended as first-line treatment when feasible [3]. In cases of isolated, asymptomatic,
non-expansive LCH without mass effect, a wait-and-see approach with close monitoring is appropriate [3]. Systemic
corticosteroids (e.g., 0.5 to 1 mg/kg/day for 6–12 months) may be considered in recently diagnosed, symptomatic
nodular forms [9,12].

Surgical excision is reserved for patients with expansive or symptomatic lesions, although recurrence may occur
despite treatment [15]. Low-dose stereotactic radiotherapy (≤22 Gy) is generally indicated in isolated localized LCH
with sporadic recurrence or in cases where surgery poses a high risk [10, 18]. Patients with pituitary involvement
and confirmed hypopituitarism require systematic hormone replacement therapy, along with regular endocrine
evaluations to detect emerging deficiencies [3,13]. In unifocal LCH where local treatment is not feasible due to
anatomical inaccessibility or procedural risks, as in hypothalamic-pituitary involvement, patients should be managed
similarly to those with multifocal disease, with systemic chemotherapy indicated [3].

In cases of multisystem LCH or extensive/refractory multifocal single-system LCH, systemic chemotherapy with
cladribine or cytarabine is recommended due to their durable remission rates and favorable safety profile [3].
Vinblastine in combination with prednisone may serve as an alternative regimen; however, it carries a higher relapse
rate and a notable risk of vinblastine-induced neuropathy [3]. Targeted therapies, including BRAF-inhibitors (e.g.
vemurafenib) for BRAF V600E mutations and MEK-inhibitors (e.g. trametinib) for MAP2K1 mutations, are
indicated in refractory LCH or in the setting of risk organ dysfunction unresponsive to first-line therapy [3].

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Langerhans cell histiocytosis (LCH) typically exhibits an unpredictable course, often progressing in relapsing
episodes. The disease may spontaneously regress or evolve into a disseminated form, compromising vital organ
function and leading to life-threatening complications [1,3]. Localized forms of LCH usually follow a slow and
indolent course, with a favorable response to treatment and a 5-year survival rate of approximately 90% [23]. In
contrast, systemic forms involving the liver, spleen, bones, or lungs, young adult patients, and lack of clinical
response within six weeks of therapy are associated with a poor prognosis [13]. This was the case in our patient,
who unfortunately succumbed to septic shock originating from a cutaneous infectious focus. The fatal outcome was
largely precipitated by profound immunosuppression, primarily due to hematologic involvement manifesting as
severe neutropenia. This highlights the critical role of immune surveillance in patients with multisystem LCH and
underscores the importance of early recognition and aggressive management of infectious complications in the
context of cytopenias.

Conclusion:-
Langerhans cell histiocytosis (LCH) is a rare disease with a wide and heterogeneous clinical presentation [1].
Involvement of the pituitary gland is often non-specific, both clinically and radiologically, which may lead to
delayed diagnosis and severe, sometimes fatal, outcomes—as seen in our case [1, 3]. LCH should be considered in
any patient presenting with abnormalities of the hypothalamic–pituitary axis, particularly when central diabetes
insipidus and anterior pituitary insufficiency are present [9]. A histological confirmation remains essential for
diagnosis, preferably through biopsy of an accessible lesion such as the skin. When no other tissue is available,
pituitary biopsy may be considered on an individual basis [3].Early recognition of LCH in atypical endocrine
presentations may improve outcomes through timely diagnosis and appropriate treatment. A thorough systemic
evaluation is crucial to identify silent organ involvement, especially in high-risk locations, and to guide
multidisciplinary management. The prognosis largely depends on the number of organs involved and the patient’s
initial response to therapy [3]. Long-term follow-up is vital, as relapses and persistent dysfunction are common and
can lead to progressive organ damage over time.

Summary Points:
 Langerhans cell histiocytosis (LCH) must be systematically considered in any patient presenting with
hypothalamic-pituitary axis (HPA) abnormalities, particularly Central Diabetes Insipidus (CDI), alone or
associated with one or more Anterior Pituitary Hormone Deficiencies (APHDs).
 Given the non-specific nature of radiological findings (pituitary stalk thickening) and the potential morbidity of
pituitary biopsy, definitive diagnosis relies on histological confirmation via biopsy of an accessible peripheral
lesion, such as the skin.
 A complete and early systemic workup (including 18F-FDG PET/CT) is crucial to identify silent organ
involvement and guide the therapeutic management.
 Multisystem LCH with involvement of high-risk organs (bone marrow and liver, as demonstrated in this case) is
associated with a poor prognosis and necessitates the rapid initiation of aggressive systemic chemotherapy.
 Infectious complications (sepsis/septic shock) are a frequent cause of mortality in multisystem LCH. Close
immunological monitoring and aggressive management of cytopenias (especially neutropenia) are vital in these
patients.
 It is essential to actively search for associated hematologic malignancies (such as myelodysplastic syndrome, as
seen in this patient) as they complicate management and can significantly influence prognosis.

References:-
1. Aricò M, Girschikofsky M, Généreau T, et al. Langerhans cell histiocytosis in adults: report from the
International Registry of the Histiocyte Society. Eur J Cancer. 2003;39(16):2341–8. [9]
2. D’Avella D, Giusa M, Blandino A, et al. Microsurgical excision of a primary isolated hypothalamic
eosinophilic granuloma. J Neurosurg. 1997;87(5):768–72. [19]
3. Diamond EL, Durham BH, Haroche J, et al. Diverse and targetable kinase alterations drive histiocytic
neoplasms. Cancer Discov. 2016;6(2):154–65. [5]
4. Diamond EL, Durham BH, Ulaner GA, et al. Efficacy of MEK inhibition in patients with histiocytic neoplasms.
Nature. 2019;567(7749):521–4. [6]
5. Goyal G, Tazi A, Go RS, et al. International expert consensus recommendations for the diagnosis and treatment
of Langerhans cell histiocytosis in adults. Blood. 2022;139(17):2601–21. [3]

176
ISSN:(O) 2320-5407, ISSN(P) 3107-4928 Int. J. Adv. Res. 13(11), November-2025, 169-177

6. Goyal G, Young JR, Koster MJ, et al. The Mayo Clinic Histiocytosis Working Group Consensus Statement for
the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease,
Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease. Mayo Clin Proc. 2019;94(10):2054–71. [10]
7. Grois N, Fahrner B, Arceci RJ, et al. Central nervous system disease in Langerhans cell histiocytosis. J Pediatr.
2010;156(6):873–81.e1. [16]
8. Kaltsas GA, Powles TB, Evanson J, et al. Hypothalamo-pituitary abnormalities in adult patients with
Langerhans cell histiocytosis: clinical, endocrinological, and radiological features and response to treatment. J
Clin Endocrinol Metab. 2000;85(4):1370–6. [11]
9. Khurana S, Sluzevich JC, He R, et al. Association between high-grade myelodysplastic syndrome and
cutaneous Langerhans cell histiocytosis suggested by next-generation sequencing. JAMA Dermatol.
2020;156(7):817–9. [18]
10. Ma J, Laird JH, Chau KW, et al. Langerhans cell histiocytosis in adults is associated with a high prevalence of
hematologic and solid malignancies. Cancer Med. 2019;8(1):58–66. [17]
11. Maghnie M, Genovese E, Aricò M, et al. Evolving pituitary hormone deficiency is associated with pituitary
vasculopathy: dynamic MR study in children with hypopituitarism, diabetes insipidus and Langerhans cell
histiocytosis. Radiology. 1994;193(2):493–9. [13]
12. Makras P, Alexandraki KI, Chrousos GP, Grossman AB, Kaltsas GA. Endocrine manifestations in Langerhans
cell histiocytosis. Trends Endocrinol Metab. 2007;18(7):252–7. [14]
13. Malpas JS. Langerhans cell histiocytosis in adults. Hematol Oncol Clin North Am. 1998;12(2):259–68. [7]
14. Malpas JS, Norton AJ. Langerhans cell histiocytosis in the adult. Med Pediatr Oncol. 1996;27(6):540–6. [8]
15. Montefusco L, Harari S, Elia D, et al. Endocrine and metabolic assessment in adults with Langerhans cell
histiocytosis. Eur J Intern Med. 2018;51:61–7. [15]
16. Pankaj P, Gupta P, Pankaj N, et al. Multifocal, multisystem presentation of adult-onset Langerhans cell
histiocytosis on 18F-fluorodeoxyglucose positron-emission tomography-computed tomography: a rare case
report. Indian J Nucl Med. 2022;37(1):78–82. [2]
17. Rodriguez-Galindo C, Allen CE. Langerhans cell histiocytosis. Blood. 2020;135(16):1319–31. [1]
18. Sconocchia T, Fosselteder J, Sconocchia G, Reinisch A. Langerhans cell histiocytosis: current advances in
molecular pathogenesis. Front Immunol. 2023;14:1275085. [20]
19. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid
Tissues. Lyon: IARC; 2017. [4]
20. Yavropoulou MP, Tsoli M, Kaltsas G. Neuroendocrine manifestations of Langerhans cell histiocytosis. Handb
Clin Neurol. 2021;181:127–35. [12]

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